The Physiology of Gestation

The intrauterine period of embryonic and foetal development in viviparous mammals is the gestation or pregnancy period. The gestation period starts after fertilisation, and the length of the gestation period is species specific (Table 23.10).

Nutrition: The lactation imposes a tremendous nutritional challenge on dairy cattle, and the cows undergo negative energy balance (NEB). The body reserves are mobilised to meet the metabolic need for milk production. Severe NEB leads to poor reproductive performances, and the first postpartum ovulation is delayed. The resumption of cyclicity within 4 weeks postpartum is economically

Fig. 23.6 Factors affecting gestation. The pregnancy success is influenced by environmental (nutrition, environmental temperature and season), genetic (species, breed and foetal genotype), maternal (maternal age, number of births, maternal nutrition) and foetal factors (litter size, sex of foetus and foetal endocrine factors)

beneficial for dairy cattle, and optimum nutrition during the immediate post-calving period is essentially required to achieve this goal with high embryonic survival.

Diseases: The incidence of diseases in livestock affects embryonic mortality. In cattle, fertility is compromised in mastitis, retained placenta, uterine infections, displaced abomasum, hypocalcaemia and ketosis.

Environment: Environmental stressors cause early embryonic mortality due to poor oocyte quality and depressed HPO axis.

Genetics: Chromosomal defects, mutation in the individual gene and genetic interactions lead to poor embryonic mortality. The genetic predisposition to early embryonic loss is implicated due to inbreeding. Brachyspina syn­drome, a rare recessive genetic disorder that develops in the cattle due to deletion in the bovine FANCI, has been identified in Holstein dairy cattle and causes embryonic mortality. Its incidence is low (gestation period, but it becomes swollen and pliable at the end of pregnancy.

23.3.1.2 Cervix

The cervical mucous becomes viscous and forms a plug to protect against infections. This cervical plug is formed under the influence of progesterone.

23.3.1.3 Uterus

The embryo spends over 98% of its gestation life in the uterus. The uterus undergoes gradual changes to accommo­date the foetus. Under the influence of high progesterone and low estradiol, the uterus becomes soft and flaccid to make a congenial environment to accommodate the foetus.

23.3.1.4 Ovary

The most prominent gestational change in the ovary is the presence of the corpus luteum that secrets progesterone. The oestrus is suspended during gestation under the influence of progesterone. In mares, the secondary CL develops between 35th and 150th day of pregnancy, which regresses along with primary CL around the seventh month of pregnancy.

23.3.1.5 PelvicLigaments

The pelvic ligaments become relaxed during the time of pregnancy. The most pronounced changes occur around par­turition under the influence of estradiol and relaxin. The relaxation of pelvic ligaments is common in cows and ewe compared to the mare.

23.3.2 Maternal Adaptions During Pregnancy

Pregnancy imposes tremendous metabolic challenges to the mother for optimum foetal growth and nutrition. An adequate supply of nutrients is essentially required for the survivability of foetuses. The mother has to undergo physiological adaptations to ensure a continuous supply of nutrients for the foetuses and to maintain the mother itself. The physiolog­ical adaption strategies during pregnancy are summarised in Table 23.13.

23.3.3 Control of Gestation

Endocrines control gestation. Nerves have no role in maintaining gestation. Progesterone is the chief hormone for maintaining gestation. Early pregnancy is controlled by the luteal progesterone in all domestic mammals. The pres­ence of embryo/conceptus influences the hypothalamus- hypophyseal tract for constant releasing of gonadotropin (luteotropin). It results in persistent corpus luteum followed by inhibition of luteolytic PGF2α synthesis and assures con­tinual luteal progesterone. The later part of the pregnancy is controlled by the placental progesterone in mare and ewe. The luteal progesterone is continued to sustain the pregnancy in other mammals. Various placental, ovarian and foetal hormones and growth factors control the different phases of gestation (discussed in detail in the following areas). Proges­terone reduces or blocks the muscular tone of the female reproductive tract, referred to as progesterone block. Proges­terone favours endometrial growth, influences to secrete endometrial gland secretion (uterine milk) and support the placentation in farm animals. Oestrogens are synthesised both in the ovary and in the placenta in low quantity during gestation to support the action of progesterone as well as udder development. At the last stage of pregnancy, with the influence of foetal pituitary and adrenal hormones, the level of oestrogens is increased, which influences the parturition process by relaxing pelvic structures, cervical dilation and promoting oxytocin (discussed details in following areas).

23.3.4 Placenta

The transient structure of mammals that connects the devel­oping foetus with the uterine wall through the umbilical cord for the physiological exchange between mother and foetus is called the placenta. It develops soon after the blastocyst implantation and expels during parturition and the foetuses. Placenta provides nutrients and eliminates waste, helping in gaseous exchange and thermoregulation. It also acts as a temporary endocrine gland and defends against infection. The placenta’s shape, structure, and configuration differences are species specific (Table 23.14) and depend primarily on the uterine structure and litter size. The mammals having placenta are also termed eutherian mammals.

23.3.4.1 Structure of Placenta

The placenta has two basic parts; the foetal part develops from the chorion of the blastocyst, and the maternal part develops from the endometrium of the uterus or maternal tissues. The placenta’s foetal parts comprise three layers: the endothelium lining of allantoic capillaries, the connective tissue of chorioallantoic mesoderm and the chorionic epithe­lium of chorioallantoic mesoderm and chorionic trophoblast. Similarly, the maternal part of the placenta also has three layers: the endothelium lining of the blood vessels, the epi­thelial cells and the connective tissue of the endometrium (Fig. 23.7a). In the chorioallantoic placenta, all three layers of the foetus are involved. Still involvements of different

Table 23.13 Maternal adaptation during pregnancy

Table 23.14 Different types of the placenta in domestic mammals

Note: Synepitheliochorial (earlier termed as Syndesmochorial) is a lack of endometrial epithelium after implantation

endometrium tissues are occurred by the influence of proges­terone and species specific, which develop various types of the placenta.

Chorion is the double-layered foetal membrane that originates from the trophoblast and extraembryonic meso­derm of the foetus that emerges into the endometrium of the uterus during pregnancy. The chorion, along with its villi together called chorion frondosum. Another structure of foe­tus involved in placentation is alantois (in plural allantoides or allantoises). Allantois (in plural allantoides or allantoises) is a hollow pouch composed of an extraembryonic tissue. It connects with the urinary organs of the foetus to act as a

Fig. 23.7 Typical features of the placenta in domestic animals. (a) Types of tissue involvement in the placenta; (b) Types of placenta according to tissue involvement. The placenta’s foetal parts comprise three layers: endothelium lining of allantoic capillaries, the connective tissue of chorioallantoic mesoderm and the chorionic epithelium of trophoblast. Similarly, the maternal part of the placenta also has three waste reservoir. In reptiles, birds, and marsupials, it helps in gaseous exchange and removal of liquid wastes of the foetus. The fusion of chorion and allantois leads to the formation of chorioallantoic placenta. In some mammals (mostly in ruminants), the chorioallantoic surface is attached to the endometrium in the form of a band-like structure called placentome. The placentome contains caruncles derived from the endometrium and cotyledon from the chorion of the foetus. The number of placentomes varies between spe­cies. In cattle, sheep and goats, the number ranges between 75 and 125; in deer, 4-6 and in giraffes, 150. The villi of the chorion remain inside the oval or circular patches inform of cotyledon for gaseous and nutrient exchange. Six layers, three from foetal or chronic and three form maternal tissues, made the placenta.

23.3.4.1.1 Paraplacental Structures

Additional or accessory structures can also form in certain species to support the general exchange processes, called paraplacental structures. These structures are generally devel­oped immediately after implantation and continue before the formation of the placenta. Still, it will continue till the end of gestation together with the placenta in some animals. The yolk sac or vitelline sac is considered one of the paraplacental structures. It is found in almost all mammals in early embry­onic life but becomes non-functional within the first trimester of gestation except in rabbits and many other rodents. It attaches to the embryo’s midgut through a layer of endome­trial epithelium and vascularised foetal mesenchyme. The layers: the endothelium lining of the blood vessels, the epithelial cells and the endometrium connective tissue. The placenta can classify based on the retention of maternal layers. All three maternal layers retain in the epitheliochorial placenta. Only uterine endothelium remains in the endotheliochorial placenta. But no layer of maternal lining exists in the hemochorial placenta

yolk sac has a vital role in exchanging iron molecules in rabbits; iron and calcium molecules in rats. Subplacenta is a paraplacental structure found in some rodents. In guinea pigs, it develops from mesenchyme and is present at the roof of the central excavation in between the placental disc and decidua. The cluster of multinuclear giant cells involves in nutrient exchange. Hematoma or hemophagous organ is another type of paraplacental structure that develops in carnivores (dogs and cats) and remains up to three-fourths of the gestational period. Hematoma or hemophagous organ has a vital role in exchanging iron-rich substances. It helps to exchange the extravasation materials of maternal blood and trophoblast cells digested maternal erythrocytes. The pigments from the degraded haemoglobin after erythrophagocytosis cause in colouration of the hematoma or hemophagous organs with a green border in dogs and a brown border in cats. The placen­tal hematoma or hemophagous areas are also involved in iron transfer in bovines, ovines and caprines. The areola is a dome-shaped paraplacental structure present in different ungulates, mainly pigs and horses, for its high absorptive capacity due to a capillary network and a cavity. The areola plays an essential role in absorbing calcium and iron (in the form of ferritin) from maternal blood. The chorionic girdle is a paraplacental structure present in horses. It starts to develop from trophoblast around day 15 and lasts about day 57 of gestation. One of the major functions of the chorionic girdle is to develop equine chorionic gonadotrophin (eCG) from the endometrial cups other than nutrient exchange.

23.3.4.2 Types of the Placenta

The placenta can classify histologically, morphologically and structurally. Histologically, the placenta can be classified into three types: endotheliochorial, epitheliochorial and hemochorial (Fig. 23.7b). In the endotheliochorial placenta, the chorionic villi of the trophoblast are attached to the endothelium of maternal or endometrial blood vessels. It is mostly seen in dogs, cats and other carnivores. In the epitheliochorial placenta, the chorionic villi of the tropho­blast are attached to the epithelial lining of the endometrial glands. It is found mainly in ruminants, horses and the lower group of primates. Synepitheliochorial (previously termed Syndesmochorial) is another type of epitheliochorial placenta where the endometrial epithelium is disintegrated after implantation by some foetus-derived mediator substances. It directly contacts the foetal trophoblast with the maternal connective tissue found in ruminants. The ruminant placenta contains many binucleated cells originating from the tropho­blast, which combine with caruncular epithelial cells to make small syncytia. Placental lactogen is synthesised from these binucleated cells. In the hemochorial placenta, the chorionic villi are attached to the mucosal lining of the endometrium, and the maternal blood vessels remain in direct contact with the chorionic epithelium of the foetus. It can directly transfer the nutrients but may lead to immune reactions in the foetus. It is present in rats, rabbits, guinea pigs, mice, humans and other higher primates. In the hemochorial placenta, particu­larly in humans, decidua is formed by decidualisation. Decidua is the modified part of the mucosal lining of the endometrium that attaches with the trophoblast of the foetus and becomes a part of the placenta. The additional or auxil­iary structure of the placenta may occasionally develop in humans to provide the blood vessels in different parts (lobes) is called succenturiate placenta. The number of lobes may be two (bilobed or bipartite), three (trilobed or tripartite) or more. It causes a risk of profuse bleeding during parturition.

The placenta can also be classified into four categories according to its morphology, i.e. shape and point of attachments between foetal and endometrial tissues. These are diffuse, cotyledonary, zonary and discoid (Fig. 23.8). In diffuse types of the placenta, nearly all the allantochorionic surface villi are involved in the placenta present in horses and pigs. In cotyledonary types, cotyledons from the chorioallan­toic surface are attached discretely to the endometrium, which is common in ruminants. The alantochorionic part of the placenta of some mammals appears like a band of tissue with the endometrium is called the zonary type of placenta found in dogs, cats and other carnivores, also in elephants. In most rodents and primates, including humans, the placenta is flat and circular disc-shaped, called discoid type placenta. In the discoid placenta, the villi of the foetal surface are attached to the maternal tissues throughout the circular plate.

Fig. 23.8 Types of placenta according to shape and attachment. On the basis of shape and attachment points, the placenta classifies into diffuse (involving the entire surface of the allantochorion), cotyledonary (mul­tiple attachment points), zonary (placenta appears as a band surrounding the foetus) and discoid (single placenta of discoid shape)

According to the structure (architecture) of the chorionic membrane and its orientation with the endometrium, the placenta can be classified into three types. The crumpled surface of the endometrium (uterine epithelium), when attached to the chorionic folds, it is called the folded placenta. It is found in the pig. In the villous placenta, three types of villi are attached in chorion; primary villi are found in tro­phoblastic columns. It branches in extraembryonic mesoderm as secondary villi and contains secondary villi tertiary villi involved in the nutrient exchange. It is found in ruminants, horses and primates. When chorionic villi are surrounded by the maternal blood vessels and form a network at the junction of the foeto-maternal junctional space, it is called the laby­rinth zone. The labyrinthine placenta occurs in carnivores and rodents.

Based on the loss of maternal tissue during parturition, the placenta can be classified into two types deciduate and non-deciduate. In the deciduate kind of placenta, the maternal epithelium, submucosa, deciduate cells and foetal placenta are shaded during parturition. The endothelial part remains in the mother’s uterus during parturition. It generally occurs in humans and monkeys. In dogs and cats, similar types of maternal tissues are lost. Non-deciduate type of placenta is found in ruminants, pigs and mares where the foetal mem­brane is shaded, no maternal tissues are expelled like the deciduate type.

23.3.4.3 Placental Exchange

The placenta is involved in the physiological exchange of various substances from mother to foetus and vice versa. It provides nutrients, oxygen, multiple bio-molecules, hormones and immune modulators from the maternal end required for foetal growth. Placenta also eliminates the meta­bolic waste products of the foetus. The placenta allows a majority of substances to pass through it. However, some substances are required to metabolise before placental exchange.

23.3.4.4 Functions of Placenta

23.3.4.4.1 Foetal Nutrition

The nutrients required for foetal growth can be categorised into histotrophs and hemotrophs. Histotrophs are the secre­tory products of the endometrial glands and the extravasation materials. Hemotrophs are the substances directly transferred from the maternal blood to the foetus through the placenta. The histotrophic and hemotrophic substances are physiologi­cally exchanged through the chorioallantoic placenta. The chorion plays a major role in exchange processes. The hemotrophic substances are generally transported to the non-areolar region of the epitheliochorial placenta.

There are several transporter proteins involved in the nutrient exchange process. Uteroferrin, a transporter protein synthesised in uterine glands, assists in exchanging the iron molecule from mother blood in pig and horse through the areola. A transporter glycoprotein, transferrin, transfers the iron molecule in the hemochorial type of the placenta like a rat, rabbit, guinea pig, mouse and human.

Various essential nutrients or bio-molecules are trans­ferred through the placenta from mother to foetus carried by the blood. During the advanced stage of pregnancy, more than 80% of the uterine blood flows restricted to the cotyle­donary areas, where nearly 15% flows to the endometrial and the rest to the myometrium.

Glucose is the major energy source for foetuses concerned with the endotheliochorial and hemochorial placenta. Glu­cose can be converted to fructose in the trophectoderm cells of epitheliochorial and synepitheliochorial placenta to pro­vide additional energy. Glucose can also be utilised for the biosynthesis of some essential substances like glycosaminoglycans, phospholipids, nucleic acids and other substances. Glucose is transported by passive diffusion due to concentration gradient and facilitated diffusion. The rate of glucose transport depends upon the foetal glucose require­ment, types of the placenta and availability of glucose transporters. Maximum glucose transportation occurs in the hemochorial placenta. The insulin-independent six hexose transporters, GLUT1, GLUT2, GLUT3, GLUT4, GLUT5 and GLUT7, play a vital role in facilitating glucose transport through the mammalian placenta. The expression of glucose transporters is species specific.

In rodents and humans, GLUT1 and GLUT3 transporters; in cattle and sheep, GLUT1, and in mice GLUT1 and GLUT2 are predominant. GLUT1 and GLUT3 are also involved in water transport and glucose in different animals. The connexin 26 glucose transporters are seen in rats and mice. Glucose can also be transported through sodium-glucose co-transporters using a sodium/potassium pump system. The sodium-glucose transporter family (SGLT) like SGLT1, SGLT2, SGLT4 and SGLT5 are involved in glucose transport. Progesterone, interferon tau, growth hormone (in late pregnancy), oestrogen (in rats) and maternal obesity influence the transport and uptake of glucose and fructose. The maternal glucose may transport to the foetal blood in the form of lactate, and the foetus utilises it as an energy source. Lactates are transported by the lactate-hydrogen ion co-transport system (the monocarboxylate transporter). The other monocarboxylates, like pyruvate and β-hydroxybutyrate, are also transported by the same system. Some dicarboxylates, like succinate, malate, fumarate, α-oxoglutarate and citrate (the intermediate products of some tricarboxylates), are transported by dicarboxylate transporters through transmembrane electrochemical sodium ion gradient.

The concentration of amino acids is generally more in foetal blood than in maternal blood. Hence, an energy­dependent active transport process is required to transport amino acids against the concentration gradient. The amino acid transporters are classified according to the type of amino acids (acidic or anionic, basic or cationic and neutral). Mainly the sodium-dependent amino acid transporters are involved in this process. The EAAC1, GLAST1 and GLT1 are the sodium-dependent transporters involved in acidic or anionic amino acids (like aspartate and glutamate) transportation in the rat. The 4F2HC is another sodium-dependent transporter involved in lysine, arginine and histidine (the basic or cat­ionic amino acids) in rats and humans. The same amino acids can be transported by sodium-independent transporters like MCAT1 in rats and CAT-4 in humans. Some amino acids (mainly the anionic amino acids) need to be converted into other amino acids before placental transport like serine is converted to glycine. The urea and ethanol are diffused passively through the placental membrane.

Various fatty acids and triglycerides and their metabolites like choline, cholesterol, steroids hormones and fat-soluble vitamins are transported through the placenta. The lipase enzyme initially hydrolyses the triglycerides into free fatty acids on the maternal surface of the syncytiotrophoblast. Some essential fatty acid transporters are fatty acid translocase (FAT), plasma membrane fatty acid-binding pro­tein (FABPpm), fatty acid transporter protein (FATP) and cytoplasmic fatty acid-binding protein family (FABP) in rats and humans. Cholesterols are transported in lipoproteins, and the energy-dependent active ABC transporters are used to transport the cholesterols. The triglycerides can be stored in the trophoblast and used for energy through β-oxidation or can transform into different polyunsaturated fatty acids.

Various nucleosides are transported by two types of pla­cental nucleoside transporters, the equilibrative and concen- trative. The equilibrative nucleoside transporters transfer both purine and pyrimidine bases. The concentrative nucleo­side transporters involve dipyridamole and nitrobenzylthioinosine transfer.

The lipid-soluble vitamins are transferred by diffusion and carrier-mediated transport process. Vitamin A is transported by retinol-binding protein. Vitamin D (1,25(OH)₂D₃) is transported faster than 25(OH)D₃. Vitamin E or α-tocopherol is transferred in small quantities, and vitamin K is mainly impermeable to the placental barrier. The water­soluble vitamins are either transported directly or form metabolites in the syncytiotrophoblast. Ascorbic acid (vita­min C) is diffused in its two metabolised form, the dehydroascorbate (oxidised state), which diffuse faster or is reduced as ascorbate. The riboflavin is transported in the form of flavin adenine dinucleotide and flavin mononucleotide transporter. The folate is transported by sodium-independent transporter, and thiamine transportation favours by Ca-dependent transporters.

Major macro minerals like sodium, potassium, chlorine, calcium, iron, magnesium, phosphorus and iodine and micro minerals like zinc, aluminium, sulphur, chromium and molybdenum transfer through the placenta. Some heavy metals like cadmium, mercury and lead can also transport through the placenta. Contaminated drinking water and food, exposure to polluted soils, industrial waste and pesticides are the major sources of these heavy metals. Sodium is transported by sodium ion-hydrogen ion exchange process, as conductance and as a co-transport system with other molecules like organic solutes and inorganic anions. Sodium acts as a co-transporter for essential nutrients like amino acids, dicarboxylates, serotonin, some vitamins and phosphates. Sodium can also be transported by a Na⁺-K⁺ pump. Calcium transports through the placenta like the intes­tinal absorption process, involving both the energy­dependent active process and facilitated diffusion. In rats and rodents, the yolk sac contains calcium transporter proteins. A magnesium pump is involved in the transporta­tion of magnesium. Phosphates and iodine are transported against the concentration gradient by a sodium-dependent active transportation process. Parathyroid hormone reduces phosphate transportation. Its transportation is modulated by sodium and amino acid concentration. Oxytocin, hCG, pro­lactin and 17β-estradiol facilitate the iodine uptake by the trophoblast cells in different species. Iron is mainly transported in the form of ferritin with the help of specific protein transporters like uteroferrin and transferring (discussed in detail in an earlier section).

Transporter proteins transport zinc in the placenta, and the placenta generally serves as a partial barrier to aluminium transportation. Hydrogen ion transportation helps maintain the acid-base balance in the foetus and placenta. The hydro­gen ions are transported mainly by sodium ion-hydrogen ion exchange process, proton pump, co-transport with organic ions like lactic acid (monocarboxylate) transportation and protein-mediated transportation (active transportation by car­rier proteins) process. Chloride ion is transported by anion exchanger, as HCO₃^- and competing with Br^-, I^-, NO₃^- and SCN^-. It is also transported by co-transporter with organic substances like taurine and serotonin. Sulphates (SO₄^2-), selenium (SeO₄^2-), chromium (CrO₄^2-) and molybdenum (MoO₄^2-) are mainly transported as anion exchangers, with HCO₃^-. Sulphates (SO₄^2-) may also act as anion exchangers to transport other substances.

The movement of immunoglobulin (Ig, antibody) depends upon the types of the placenta. In hemochorial types of the placenta, the IgG can transport to the foetus through Ig-binding proteins through endocytosis. No Igs are generally transported to the foetus in the epitheliochorial and endotheliochorial placenta. The offspring of the mammals having epitheliochorial and endotheliochorial placenta are received the Igs through colostrums. In carnivores (dogs and cats), some Igs can be transferred in a minimum quantity from mother to foetus in the last trimester of gestation. It moves through a hemochorial placental structure.

Bilirubin and various drugs are generally lipophilic and transferred from the foetus to maternal blood without metab­olism as an unconjugated form. Such substances may be metabolised in the foetal liver and develop a conjugated form (like conjugated-bilirubin). The metabolised conjugated substances are transported inadequately due to their water­soluble property. Hence, the inability of the foetal liver for its improper metabolism facilitates the excretory substances from the foetus.

23.3.4.4.2 Gaseous Exchange

The gaseous exchange usually takes place through the cho­rion. Fully oxygenated blood is entered into the placenta from maternal circulation through uterine arteries. The uterine artery gives rise to numerous spiral arterioles that open into the intervillous space. Deoxygenated blood from the foetus is first carried to the placental circulation and then communicates with uterine veins. The chorionic villi and umbilical arteries are situated in the intervillous space. At this site, both the oxygenated and deoxygenated blood comes. Still, due to placental oxygen uptake, a partial pres­sure gradient is established where the intervillous space has a lower partial pressure of oxygen than the maternal blood. The endothelin and prostanoids have a vasoconstriction role, whereas nitric oxide causes vasodilatation. The foetoplacental circulation is susceptible to hypoxia, which leads to excessive free radicals resulting in pre-eclampsia and other pregnancy complications. Melatonin has an antiox­idant role in the placenta.

Further, the oxygen-carrying capacity of foetal haemoglobin is more than mother haemoglobin in most domestic mammals. Foetal haemoglobin is absent in horses, dogs, rabbits and mice. The carbon dioxide is exchanged between maternal and foetal tissues through the placenta due to partial pressure differences.

23.3.4.4.3 Endocrine Role of the Placenta

Placenta produces several steroid and glycoprotein hormones that promote foetal growth and modulate the maternal

physiological system in terms of ovarian activity, growth of the mammary gland and parturition. The placenta produces several cytokines, but placental hormones are generally used as a biological marker for confirmation of pregnancy. Placen­tal hormones are categorised into four types according to their production and action, steroid hormones, prolactin­growth hormone-related hormones, neuroactive hormones and other groups of hormones (Table 23.15). The interaction of placental hormones and growth factors and maternal physiological adjustment is important for maintaining preg­nancy and optimum foetal growth.

Table 23.15 Interaction of placental hormones and growth factors during pregnancy in rodents and primates, including human

References: Petraglia et al. (2010), Feng et al. (2016), Napso et al. (2018)

Note: The expression profile of the hormones is demonstrated considering the total gestational period in three trimesters (first trimester, second trimester and third trimester as 1T, 2T and 3T, respectively). The upward arrow marking (") indicates up-regulation. Single, double and triple arrow (s) denote(s) the intensity of responsiveness. E2 oestrogens, P4 progesterone, PRL prolactin, PL placental lactogen, GH growth hormone, GHRH growth hormone releasing hormone, IGF2 insulin-like growth factor 2, PLF proliferins, PRP proliferin-related proteins, OXY oxytocin, MEL melatonin, SER serotonin, KISS kisspeptin, TRH thyrotropin-releasing hormone, REL relaxin, CG chorionic gonadotropin, ACT activin, LEP leptin, PTHrP parathyroid hormone-related protein

23.3.4.4.3.1 Placental Steroids

Two major steroid hormones, progesterone and oestrogen, are produced from the placenta and modulate the functions of the endometrium. Pregnenolone is the precursor of both oestrogen and progesterone produced from cholesterol in uninucleated trophoblast epithelial cells (UTC), and proges­terone is synthesised either in binucleated dominated tropho­blast giant cells (TGC) or foetal cotyledons with the help of cytochrome P450SCC in UTCs and 3β-hydroxysteroid dehy­drogenase in the TGCs or, foetal cotyledons or, maternal caruncles. The maternal caruncles have more steroidogenic activity during the latter half of gestation, mainly in cattle. The progesterone thus produced is transported to both mater­nal and foetal systems. The permeability of progesterone in maternal tissue and foetus is almost the same in mammals. Still, the progesterone level is generally less in the foetus than in maternal tissue due to more metabolism. The progesterone is converted into 20α-hydroxy-progesterone by the 20- α-hydroxysteroid dehydrogenase enzyme (20α-HSD). It is mainly expressed in foetal cotyledons during late pregnancy and before parturition. Hence, it is metabolised before the diffusion of progesterone to maternal caruncles. In sheep, placental progesterone synthesis is biphasic, once in 50-70 days and another in 90-120 days of gestation. The placenta can produce sufficient progesterone after 150-200 days of pregnancy in horses and after 6 weeks in women independent of CL. Equine placental steroidogenesis is unique. Initially, the luteal progesterone produced by the influence of eCG supports placental and foetal growth during the first phase of pregnancy. Later, foetal pregnenolone and dehydroepiandrosterone (androgen) appear in the placenta and act as the major substrates to synthesise the 5-α-pregnanes and oestrogen-like compounds, respectively. In rats and mice, three types of steroids, progesterone, testos­terone and oestrogens, are produced from the placenta in different phases. Placental testosterone is used as the precur­sor of progesterone and oestrogens. The level of placental progesterone production peaked during half of pregnancy (around 12 days of gestation), followed by a decline from day 14 to base within day 16. In humans, estriol and a tiny amount of equilin are synthesised. For some animals, like a dog, no additional steroid is required for maintaining pregnancy.

Progesterone acts as muscle relaxant and local immuno­suppressive agent. It also involves endometrial differentiation and closure of the cervix. Progesterone also influences the HPO axis to reduce the secretion of FSH, followed by inhibi­tion of oestrogen, LH surge and ovulation. Progesterone suppresses glucocorticoids and inhibits the prolactin receptor in mammary glands.

Placental oestrogen is oestrone in nature in contrast to ovarian estradiol in most of the higher groups of mammals. Mare can also synthesise other oestrogenic compounds like equilin and equilenin from the placenta. The horse’s placenta has a deficiency of 17α-hydroxylase enzyme and a higher level of 3βHSD and CYP11A1; hence, foetal androgen is utilised to produce oestrogenic compounds like equilin and equilenin during pregnancy. The level of the oestrogenic compound during pregnancy is found to occur maximum in mares among the various domestic mammals. In cattle, the oestrone is generally produced as an inactivated form of oestrone sulphate, converted to active oestrogen by an enzyme steroid sulfatase (StS) in the caruncular epithelium. The foetal adrenal gland controls the rate of production and metabolism of placental oestrogens. The foetal adrenal is responsible for the activation of 17α-hydroxylase (a placental cytochrome P450) required in the oestrogen production pathway. Under the influence of 17α-hydroxylase and aromatase, foetal androgen, placental progesterone and other steroidogenic precursors are converted into oestrogenic compounds during steroidogenesis. Hence, the production rate of oestrogens in the placenta increases when the foetal pituitary-adrenal axis is matured at the late stage of gestation. Oestrogen is mainly responsible for the growth of endome­trium and myometrium along. It also controls uterine blood flow during the pre-implantation period and at the time of parturition to increase the myometrial tone. During preg­nancy, oestrogen also facilitates mammogenesis in some animals like horses, rats and mice. It enhances progesterone sensitivity, the production of prolactin, IGF-1 and phospholipids, regulates salt and water retention and has a crucial role in foetal neuroendocrine development, digestion, energy storage and other chemical homeostatic mechanisms. It influences maternal behaviour and controls the parturition process.

In domestic eutherian mammals, uteroplacental tissues can produce prostaglandin (PGF2α) immediately before par­turition at the last stage of pregnancy. It is due to progester­one and oestrogen ratio alteration and activation of prostaglandin-endoperoxide synthase 2 (PGHS-2). The PGHS-2 is one of the major inducers for the synthesis of PGF2α, which is suppressed during gestation. The major roles of PGF2α are to increase contractility of the myometrium, destruction of the chorioallantois, partition of the placenta from the uterine attachment, and uterine involu­tion and cervical dilatation.

Hence, the abundant oestrogenic and progestin compounds are formed simultaneously from the equine “foeto-placental unit”, a rare phenomenon in domestic mammals. The increased level of pregnane from mid-pregnancy, followed by a reduced level immediately before parturition, is controlled by the presence of the recep­tor for pregnane.

Testosterone is mainly available in the first half, mainly from the ovarian source, where the placenta becomes the major source in the second half. As a result, testosterone level gradually increased and attained a peak a few days earlier to parturition (about day 18), then declined. Low levels of oestrogens are also produced in the placenta; these are 20 alpha-hydroxy-4-pregen-3-one and 17 beta-estradiol.

23.3.4.4.3.2 Placental Protein Hormones

The placenta produces several protein hormones. Major pla­cental protein hormones are placental lactogens, chorionic gonadotropins and relaxin.

Placental lactogens (PL) are structurally similar to growth hormones and prolactin. It is synthesised in the trophoblasts of ruminants, rodents and primates. The terminology of pla­cental lactogen based on species like bovine placental lactogen is known as bPL, sheep (ovine) as oPL, rat as rPL, mouse as mPL, hamster placental lactogen haPL and human as hPL. The bPL generally appears from 4 months of preg­nancy. The oPL secrets from day 50 of gestation and continue to produce large quantities throughout the pregnancy. The rate of production of rPL and mPL is correlated with the litter size. The mPL is generally three types mPL-I (Prl3d1, pro­duced at mid-pregnancy), mPL-II (Prl3b1, produced at latter half of pregnancy) and mouse PRL (prolactin). The rat can also make a variety of rPL, like PLI (Prl3d4, produced in the latter half of pregnancy). The PL is produced under the influence of prolactin and somatotropin-linked genes in ruminants and primates, respectively.

In humans, the chorionic somatomammotropin genes (ICSH-1 and ICSH-2) are involved. Several growth factors, depending on species, influence the synthesis of PL. It is influenced by IGF-1, angiotensin II, phospholipase A2 and epidermal growth factor in humans.

The PL is considered to involve in mammary gland devel­opment (mammogenesis) together with IGF-1, epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). It influences maternal angiogenesis. It can also affect the mobilisation of the nutrients to the foetus during pregnancy by inhibiting maternal insulin. Gestational diabe­tes is the consequence of this insulin resistance due to PL. The glucose, amino acids, free fatty acids and ketone bodies are mainly transferred to the foetus by the influence of PL. The PL, along with prolactin, influences the choroid plexus and brain to induce maternal behaviour during pregnancy by altering the neural processes during the pregnancy and post­partum period. The PL is also involved in modulating auto­immune reactions and cell-mediated immunity and is associated with thymus and bone marrow functions. The PL, in combination with progesterone and prolactin, stimulates erythropoiesis. The PLI and PLII enhance proges­terone synthesis by reducing the expression of 20- α-hydroxysteroid dehydrogenase (20α-HSD).

Chorionic gonadotropin (CG) is produced from trophoblasts and has functional similarities with pituitary gonadotropins. It is secreted in the horse (eCG, previously regarded as pregnant mare serum gonadotropin, PMSG) and primates, including humans (hCG). The mouse can also produce chorionic gonadotrophic with functional similarities with hCG, and its production rate is relatively increased with the litter size. The level of CG is increased from the stage of implantation. Hence, the presence of CG in urine or blood confirms the pregnancy at a very initial stage. The hCG acts over the LH-R in the corpus luteum, supporting its life span and preventing regression. Hence, hCG provides maternal recognition of pregnancy in humans, like interferon tau in ruminants. The eCG is structurally and functionally similar to LH. It is synthesised from the chorionic girdle, a special glandular structure and endometrial cups of the mare. The eCG appears at the end first month (from around day 25) of gestation and continues up to 3-4 months. It supports the primary corpus luteum to generate progesterone. It also influences the development of supplementary corpora lutea in mare.

The placenta is the major source of a polypeptide insulin­superfamily hormone, relaxin, produced from the trophoblast of the foetus. It appears from 12 weeks in the mare and reaches a peak at mid-pregnancy that corroborated with the levels of PL of cats and dogs where relaxin appears after third (reached peak at the 36th day) and fourth weeks of preg­nancy, respectively. The concentration of relaxin rapidly declines at parturition. The Corpus luteum is the major source of relaxin in other mammals. In cattle and sheep, relaxin-like hormone, the insulin-like peptide 3 (INSL3), is produced in the corpus luteum. In the horse, trophoblast has enzyme furin which converts preprorelaxin into relaxin. The major functions of relaxin include endometrial angiogenesis through vascular endothelial growth factor (VEGF), relaxa­tion of pelvic ligaments and pubic symphysis and cervical dilatation to facilitate parturition. It also involves the remodelling of the extracellular matrix. Relaxin can influence the growth of the uterus, vagina and cervix in late pregnancy in the pig.

23.3.4.4.3.3 Placental Proteins

The placenta of rodents can produce some luteotrophic PRL-like proteins, such as proliferin (Prl2c2) and proliferin- related protein (Prl7d1) from giant cells and cytotrophoblasts, respectively. Ruminants and rodents can produce several prolactin-related proteins (PRP) from the placenta. The pla­centa can secrete about six types PRPs in bovine (bPRP) and sheep (oPRP), 22 types in rat (rPRP) and mice (mPRP). The goat also secretes PRPs (cPRP) from the placenta. PRP helps in implantation, placentation and maintenance of pregnancy.

The trophoblastic cells and syncytium of sheep and goats and trophoblast of humans can produce placental growth hormone. It secretes from day 27 to 75 of pregnancy in sheep, with a peak at day 40-45. The human placental growth hormone is generally produced up to the second trimester, and then its activity is replaced by pituitary growth hormone. In early pregnancy, the placenta can produce some pregnancy-associated glycoproteins (PAG) in cattle (bovine placental specific protein, BPSP), sheep, goats, pigs, horses and mice. The PAGs belong to the pepsin-like protein family but have no enzymatic role. It is secreted from the trophectoderm in ruminants and involved in immunoregula­tion at maternal-foetal interaction during pregnancy. It is also used to identify the pregnancy in ruminants. The rodents and human placenta can synthesise an enzyme 11- β-hydroxysteroid dehydrogenase (11β-HSD2), which can protect the foetus from the high level of glucocorticoid by inactivating cortisol. The rodents produce it from mid-pregnancy, and in humans, it continues throughout the gestation. Hence, stress can affect pregnancy in rodents and humans. The human trophoblast cells can produce unique microRNAs (miRNAs), known as trophomiRs that suppress the maternal immune response against the developing foetus. In humans, it is usually used as a biomarker for some preg­nancy disorders like pre-eclampsia and foetal trisomy 21.

The placenta of different animals secretes various types of peptide hormones, like inhibin A, activin A, adipokines and TGF-β superfamily proteins. Some neuropeptides like a gonadotropin-releasing hormone (GnRH), corticotropin­releasing hormone (CRH), thyrotropin-releasing hormone (TRH), somatostatin and ghrelin are also synthesised from the placenta. The placenta is also involved in the synthesis of many growth factors, like IGFs (from endometrial cells) and vascular endothelial growth factor (VEGF) under the influ­ence of CG. The growth factors facilitate angiogenesis and placental exchange, and CRH involves steroidogenesis. Pla­centa produces cytokines like interleukin-8 (IL-8) and tran­scription factors (NF-B) from epithelial cells, cytotrophoblast cells and fibroblasts interacting with the immune cells. All are involved in the regulatory network for foetal growth, placen­tal development and parturition. It is considered that cytokines derived from maternal adipose tissue and placental cells are originated from common molecules and involved in similar inflammatory events.

23.3.4.5 Placenta in Different Animals

23.3.4.5.1 Pig

The chorion and allantois grow rapidly during days 18-30 of pregnancy and fuse together within day 60. The exponential growth of the placenta continues up to day 70. The angio­genesis and the capillary bed are increased in the last 40 days of gestation. The allantochorion surface is highly folded to make ridge-like structures that adhere to the endometrium’s grooves. The fold of the chorion builds a special structure called areolas made by trophoblasts cells that receive the endometrial secretions and are involved in erythrophagocytic activity and iron transportation from the degraded haemoglobin.

23.3.4.5.2 Horse

Structural characteristic of the horse’s placenta is similar to a pig. The trophoblast of the horse forms a narrow band-like structure (later, chorionic girdle) at the junction between allantois and yolk sac. Later, it develops into ridges followed by glands from where the eCG secrets. The glands transformed into a decidua-like cell special structure, the endometrial cup. The glands hold the chorionic girdle in position, and the girdle starts to increase rapidly. The hyperplastic girdle cells gradually invade the endometrial epithelium, basement membrane and uterine stroma within day 40 of pregnancy and form eCG-secreting endometrial cup cells. The endometrial cups reach their maximum size within days 55-70 of gestation, having round shaped binu­cleated cells with maximum secreting capability. The leuko­cyte accumulation progressively occurred immediately after the maturation of endometrial cups from days 70 to 80. The B cells, T cells and various macrophages destroy the cups within days 100-140 of gestation. The major histocompati­bility (MHC) class I antigen is potentiated by the immuno­logical destruction process. Failure of development of endometrial cups within day 70-80 causes abortion. Mare bred with donkey develops one supplementary corpus luteum, whereas breeding with horse results in 2-3 corpora lutea. The supplementary corpus luteum formation generally starts around days 20-25 of gestation in horses. Both the primary and supplementary corpora lutea are regressed around 26 weeks, but placental progestagen (5-α-pregnanes, metabolite of progesterone) production is continued.

23.3.4.5.3 Dogs and Cats

Implantation is centric and anti-mesometrial, and the placenta is zonary-endotheliochorial in dogs and cats. The endometrial epithelium degenerates during implantation to form syncytiotrophoblast or syncytium at the centre of chorioal­lantois. The syncytium enters the endometrial epithelium and attaches to the endothelium of the maternal capillaries. The invading villi of the foetus later unite together to form a labyrinthine-type placenta. The dog placenta has a labyrinth zone and the junctional zone, sponge zone, glandular zone and hemophagous zone. The region between the labyrinth and gland zones is called a junctional zone. The trophoblast of this transitional area invades the endometrial gland cavity and contains a single layer of tall columnar cells with microvilli. The deep part of the junctional zone is termed as sponge zone. The placenta in dogs has hemophagous zones located on both maternal and foetal ends of the placenta, having high columnar trophectoderm involved in active phagocytosis, digestion of erythrocytes and iron transportation.

Both the dogs and cats have paraplacental structures, hematomas for its nutrients exchange. The pregnancy is maintained in the dog by the luteal progesterone and depends upon the pituitary gonadotropin (LH) prolactin. Hence, con­firmation of pregnancy by measuring progesterone level is difficult in the dog, where corpus luteum is persisted more than during the pregnancy period in pseudopregnancy. The progesterone level can also confuse to confirm the pregnancy or pseudopregnancy in cats. The cat placenta can start to produce progesterone at around 3 weeks of ovulation, which may be perplexed when a luteal cyst exists. However, progesterone level is reduced initially at 10-12 days of ovu­lation in a pseudopregnant cat due to low StAR and 3βHSD mRNA expression though its expression is further increased from mid-pregnancy. Relaxin is synthesised in the placenta from about 4 weeks in dogs and cats. Hence, relaxin can be used to determine the pregnancy in dogs and cats.

23.3.4.5.4 Rodents and Humans

Both the rodents and humans have histologically hemochorial and morphologically discoid type placenta, but structurally humans and primates have a villous type, whereas rodents contain labyrinthine type placenta. The maternal blood comes into direct contact with foetal chorion without fluid exchange due to low blood pressure, resulting in backflows of deoxygenated blood through endometrial veins. The placental exchange is similar mainly in rodents and humans because of their histological similarity. It has three layers between maternal and foetal blood vessels, which resemble the maternal-foetal counter-current arrangement. But the trophoblastic epithelial cell layer does not remain uniform throughout the gestational period in rodents and humans. The trophoblastic layer is gradually reduced during different stages of gestation in humans. Three layers exist during the entire pregnancy period in rats and mice, termed haemotrichorial whereas two layers are persisted in rabbits and the first trimester of human pregnancy, regarded as haemodichorial; and a single layer is present in guinea pigs and the last two trimesters of human pregnancy, known as haemomonochorial. Hence, placental exchange in humans during the first trimester of pregnancy can be compared with rabbits, and the last two trimesters can be compared with guinea pigs. Thus, in various research trials of drugs and other bio-molecules, the rabbit and guinea pig model is used instead of the human, according to the stage of gestation. Different immunoglobulins are transferred through the chorio-allantoic placenta in humans, whereas it occurs in rodents through the yolk sac. Within rodents, the trophoblas­tic invasion of the maternal arteries is also variable. More invasion of trophoblast occurs in rats and guinea pigs than the mouse.

23.3.4.6 Foetal Sex-Specific Placental Activity

Presence or absence of sex-bearing Y chromosome in foetus influences the placental responses in some animals, including humans. It is due to the presence of some specific coding genes that demonstrates sexually dimorphic differences and influence the growth and development of the placenta and foetus. The specific coding genes influence the production of placental and manipulate the function of steroids, neuropeptides (serotonin, melatonin and oxytocin), prolactin, growth hormone and various growth factors (including pla­cental lactogen and IGF). It results in up- and-down-regula- tion of the flow of different nutrients and other essential proteins through the placenta.

In cattle, buffalo, sheep, goats and other ungulates, the presence of a female sex-bearing foetus influences the greater expression of interferon tau (IFN_t) than in males. Hence, the signal for maternal recognition of pregnancy is better expressed in the female sex-bearing foetus, caused to influ­ence more anti-luteolytic effects. The male sex-bearing foetus grows faster than the female foetus by enhancing metabolism and amino acid transportation in cattle, like all other euthe­rian mammals. In mice, breed-specific characteristics changes occur. The placental growth and metabolic rate are up-regulated in male spiny mouse foetus than in female foetus by influencing glucose transporter, nutrient supply, cell growth and other systems with the dynamic changing of specific genes like glucose transporter protein type 1 (Slc2a1 or Glut1), insulin-like growth factor 1(Igf1r), mitogen-activated protein kinase kinase 1 (Map2k1) where the expression of said genes are fixed pattern in the female foetus. The olfactory sense is up-regulated more in female NIH Swiss mice with a higher expression of olfactory recep­tor 154 (Olfr154). The same mouse can express more steroid receptors (Esr1 and Ar) in the female foetus.

In contrast, the male foetus-bearing placenta up-regulated more Prl gene for luteotrophic prolactin functioning resulting in better maternal recognition of pregnancy in mice (opposite nature to ungulates). The female foetus-bearing rabbit up-regulates the Lxra gene, causing more mobilisation of fat, whereas the fats (triglycerols) are accumulated more in the male foetus-bearing placenta. In humans, female foetus­bearing placenta expressed more hcg and interferon tau (IFN_t) gene causing better maternal recognition of pregnancy by more luteotrophic action than male foetus-bearing pla­centa. The male foetus-bearing placenta is more susceptible to uterine infection and maternal stress. It is due to the up-regulation of glucocorticoid receptor alpha (GRαD2) causes more metabolisms of glucocorticoids by increasing the 1β-hydroxysteroid dehydrogenase (11β-HSD2) enzyme in male foetus-bearing placenta. In addition, the female foetus-bearing placenta can also up-regulate specific genes to generate more immune responses against infection, like JAK1, IL2RB, Clusterin, LTBP, CXCL1 and IL1RL1, where

the similar genes are down-regulated in male foetus-bearing placenta. The renin-angiotensin system is up-regulated, due to ACE1 and ACE2 gene expression in deciduas, causing alteration in blood pressure and sodium reabsorption, in both the foetus and mother, having a female foetus compared to the male foetus. Thus, the male foetus-bearing mother is more prone to hypertension (diastolic pressure) than the female foetus-bearing mother.

23.3.4.7 Foetal Growth

Foetal growth has a tremendous influence on animal produc­tion. Low birth weight is associated with reduced energy reserve and low thermoregulatory activity, which leads to neonatal mortality. However, the greater bodyweight of calves also creates a parturition hindrance. Foetal growth is influenced by the number of foetuses (birth weight is inversely related to the number of foetuses), sex of foetuses (male foetuses have higher growth than females), age and parity of the cow (birth weight and parity are directly propor­tional). Foetal growth is decreased in heat and increased in the cold. Inadequate nutrition of the mother also negatively affects foetal growth. The foetal length is measured by crown-rump length (CRL), which indicates the normal growth of the foetuses. It is the straight length from the occipital magnum to first caudal vertebra. The age of the foetuses (in a month) can be calculated from CRL (in cm) by a formula.

Different events of foetal growth in bovines with gesta­tional age are depicted in Table 23.16.

23.3.4.8 Foetal Fluids

23.3.4.8.1 Amniotic Fluid

It is a hypotonic, clear, colourless mucoid fluid situated within the amniotic cavity. The predominant source of amni­otic fluid is the urine through foetal swallowing, foetal lung secretions and foetal nasal and buccal are also added to amniotic fluid. The components of amniotic fluid in a full­term human foetus are foetal urine: 800-1200 mL/day, foetal lung liquid: 170 mL/day, oral-nasal secretions: 25 mL/day, intramembranous flow: 200-400 mL/day, and foetal swallowing: 500-1000 mL/day. In the first trimester, AF is isotonic to maternal plasma. AF composition changes as foetal urine are added to amniotic fluid in humans during the second half of pregnancy. In cattle, the protein content of AF increases during the second and third trimester of preg­nancy. The level of creatinine and urea increased as the gestation progressed. Excess AF accumulation leads to a pathological condition called polyhydramnios or

Table 23.16 Events of foetal growth in bovines

Source: Pohler et al. (2020)

hydramnios. The volume of amniotic fluid varies with spe­cies. The volume of AF is 5-6 L in cattle, 3-7 L in mare, 350-700 mL in sheep, 400-1200 mL in goats, 40-200 mL in sows and 80-100 mL in dogs. Amniotic fluid protects the foetus from external shock, prevents adhesions, and aids in parturition by providing lubrication to the birth canal. The removal of amniotic fluid is done by amniocentesis to evalu­ate foetal pathology.

23.3.4.8.2 Allantoic Fluid

It is a clear, viscous and amber coloured fluid. It derives from foetal urine and secretions from the amniotic membrane. It contains a low Na, Cl and glucose level and a high K, Mg, fructose, creatinine, urea and uric acid. The volume of amni­otic fluid increases with gestation age. Allantoic fluid volume is 4-5 L in cow, 8-20 L in mare, 500-1500 mL in the ewe, 100-200 mL in sow, 10-50 mL in bitch and 3-15 mL in the cat. Allantoic fluid stores the foetus’s excretory products and helps maintain the osmotic pressure of foetal plasma.

23.3.4.9 Foetal Growth Restriction (FGR) or Intrauterine Growth Restriction (IUGR)

Foetal growth restriction (FGR) occurs when intrauterine foetal growth is restricted or retarded due to congenital abnormalities or pathophysiological alterations. FGR can be developed for several reasons like hypoxia, hyperthermia and other pathophysiological conditions that interfere with mater­nal nutrient transfer. Certain hormones and growth factors control the transportation of nutrients. Hence, by assessing these hormones and growth factors, the FGR can be evaluated along with the direct measurement of the foetuses. The genetic abnormalities to cause GFR can be evaluated through the expression of certain species-specific genes.

In mice, the extracellular signal-regulated kinase 3 (ERK3) genes are responsible for visceral growth. In humans,

placental protein regulators CSH1 (chorionic somatomammotropin hormone 1, placental lactogen) of Syncytiotrophoblasts origin and KISS1 (kisspeptin 1, metasta­sis suppressor); of cytotrophoblasts, origin, and PEG10 (paternally expressed 10) are used to predict FGR.

23.3.4.7 Factors Affecting Gestation Length

Major influencing factors on gestation can be categorised as genetic, maternal, foetal and environmental (Fig. 23.6). Ges­tation length is variable in different species (Table 23.10), breeds and foetal genotypes. Generally, the larger species have a longer gestation length. Breed variation is also noticed within a species, like the gestation length of the medium­wool and meat-type breeds of sheep ordinarily have a shorter gestation period than the fine-wool breeds. The ewes bred to white-faced, wool-breed rams generally exhibited a little longer gestation period than those bred to black-faced and meat-type rams. Season of breeding may affect the gestation length in the same species, particularly in the horse (Marwari mares). Different genotypes of the foetus affect the gestation length. The gestation period of mare X stallion is 320-350 days, whereas in mare X jack donkey (mule), it is 360-380 days, and jenny donkey X stallion (hinny) has a shorter gestation length than the horse.

Age of dam is an important maternal factor that causes variation in gestation length. Generally, the young have a slightly shorter gestation length than the older. The parity also has an effect. Litter size, foetal sex and endocrine disturbances also modulate the gestation length. A large litter size reduces the gestation length. Thus, polytocous animals have a shorter gestation length than monotocous animals. The occurrence of twin foetuses in monotocous animals causes to generally 5-6 days shorter gestation length. Male foetuses usually have 1-2 days more gestation length than female foetuses. Anterior pituitary and adrenal hormones of the foetus are involved in the initiation of parturition at the end of gestation. Nutrition and season are the two important environmental factors influencing the gestation length. Sea­son causes severely affect the gestation length in seasonal breeders like the mare, when conceived in late summer or autumn, reduced the gestation length than those conceived in early spring. Malnutrition in the dam can reduce the gestation length. Poor nutrition, particularly during the last half of gestation, affects birth weight and survivability. Deficiency of Vit A and iodine increase the gestation length.

23.4