Pregnancy and prenatal development in animals

Gestation is a period of intrauterine development in animals that are viviparous, meaning “bringing forth living young.” The word “pregnant” comes from the Latin praegnans, meaning “before giving birth.” Intrauterine development is important for several reasons. The uterus provides a unique environment that facilitates fetal development. A fertilized egg cannot live outside the uterus. The pregnant female sustains a completely undifferentiated single cell in the form of a fertilized egg through the stages of embryonic differentiation to that of a fetus capable of living outside the uterus. Proper temperature is maintained, the necessary fluids and nutrients are provided, wastes are removed, attacks by microorganisms are prevented, oxygen is supplied in a form useful to the embryo, and other compounds essential for cell growth are present.

The uterus is normally a haven with all the accommodations needed for the new potential animal. Because gestation is concealed inside the body, myth and mystery have historically surrounded the process. Modern advances have dispelled some mystery. In general, larger animals have longer gestation periods. For example, elephants are pregnant for eighteen to twenty-two months, while mice may give birth after nineteen to twenty-one days. The shortest known gestational period is twelve days, which occurs in the Virginia opossum. Conversely, guinea pigs have exceptionally long gestational periods for their size of between fifty-nine and seventy-two days. Another gestation length indicator is breeding behavior. Animals that only breed during a specific season have shorter gestational periods than those that breed year-round. Metabolic rate, environmental conditions, and the animal's required level of development at birth also influence gestational lengths. The present knowledge has been obtained from research and observations on laboratory and domestic animals, supplemented by observations on humans. The mechanisms of maintenance of pregnancy, number of young, length of gestation, anatomy of the uterus, and hormones vary considerably between species, thus preventing generalizations that might apply to more than a few species.

The Course of Pregnancy

Pregnancy begins when the recently ovulated egg is fertilized by sperm in the upper segment of the oviduct. Depending on the species, the fertilized egg resides in the oviduct for forty to one hundred twenty hours before being transported to the uterus. At a particular time during that interval, upon the laying down of certain fundamental tissues, it is referred to as an embryo. The rate of passage is influenced by the concentration of hormones in the mother. Normally, estrogen production from the ovary is great before fertilization when progesterone is not produced. After ovulation, the corpus luteum forms on the ovary, estrogen declines, and progesterone rises. This sequence permits the embryo to enter the uterus when the uterus is ready to support it. Progesterone will cause the oviduct to relax and allow the embryo to enter the uterus. Administration of large amounts of progesterone by injection will cause the oviduct to relax prematurely, and embryos will enter the uterus in eight or ten hours. High concentrations of estrogen, on the other hand, will cause the embryos to be retained in the oviduct for many days. Estrogen and progesterone also have a profound influence on the nature and function of the lining of the uterus. Estrogen causes rapid growth and, in synergism with progesterone, causes the proliferation of glands lining the uterus. These glands secrete a complex of the compounds necessary for embryonic growth and development, called “uterine milk,” for the nourishment of the young embryo before it becomes attached to the uterus.

The embryo must, in some way, make its presence known to the mother’s constitution so that the uterus continues to be a hospitable environment for the entire gestation. There are a great variety of ways that have evolved in different species to maintain pregnancy. The act of mating will cause a female rabbit to ovulate and maintain a pseudopregnancy for about eighteen days. Signals from the fetus take over during the next thirteen days to maintain the corpora lutea. If the mating was not a fertile one, the rabbit will mate again about eighteen days after the first mating. Rats normally have recurrent periods of estrus every four or five days. Mating will delay the next estrus for about twelve days. When the mating is fertile, the fetus provides signals for maintenance for the remaining nine days of gestation. Without mating, around 80 percent of unspayed females become pseudopregnant at least one time in their lives. This pseudopregnancy can extend as long as the normal gestation period of about sixty-five days. In these cases of pseudopregnancy, the hormones present, changes in the uterus, and maternal behavior are very similar to a normal pregnancy that would produce live young.

In many animal species, the interval between ovulations is somewhat prolonged by the spontaneous formation of one or more corpora lutea if there is no pregnancy. Examples include sheep, seventeen days; horse, pig, goat, cow, twenty-one days; and human, twenty-eight days. In each of these cases, the embryo must signal the mother to establish the pregnancy several days before the next expected ovulation. Embryos of some species produce estrogens that are thought not only to cause uterine growth and enlargement to accommodate the growing fetus but also to maintain the corpora lutea. In all species, the corpus luteum is necessary to produce progesterone during at least the first one-third of gestation. In the goat, pig, rabbit, and rat, the ovaries and the corpora lutea are essential throughout the gestation period. Progesterone is essential throughout gestation in all species, but in sheep and humans, the fetus and placenta supply progesterone for the maintenance of pregnancy after about fifty-five days, even when the ovaries are removed. In summary, estrogen and progesterone are both essential for several functions of pregnancy. The source of these hormones can be either or both the ovaries and placenta, with variation among species.

The Uterine Environment

Embryos arriving in the uterus must have not only sustenance in the form of an ever-changing, compatible, fluid environment, but also a place and space to develop. In species with only one young born, this may not seem to be a problem, but in litter bearers (with as many as ten per birth), it is important that each embryo has sufficient space. In the pig, the uterus is V-shaped, with the ovaries at the tips. The two uterine horns form the sides of the V, and the body of the uterus and the birth canal consisting of the cervix and vagina are at the bottom. One uterine horn may be as long as 150 to 200 centimeters. The fetuses each occupy a segment of the uterus about 30 centimeters long; thus, they are arranged like peas in pods with two horns. The embryos enter the uterus forty-eight hours after ovulation at the four-cell stage. Embryos cannot move by themselves, so the motility of the uterus helps intrauterine migration. Embryos gradually move down each uterine horn during the period from day two to day nine when they reach the body of the uterus. From day nine to day twelve, some of the embryos continue to move into the other uterine horn. Some embryos arise from one ovary implant in the uterine horn on the side of the ovary of origin, while others migrate through the body of the uterus to the other side. Movement stops on day twelve when the embryos cannot move farther.

During this period of distribution, the embryo is dividing and growing. On day six, the embryo is about thirty-two cells and is still compact, resembling a tiny raspberry or morula about two hundred microns in diameter. The embryo forms a hollow ball of cells called a blastocyst at days seven and eight. Some of the cells of the blastocyst are destined to become the new fetus, and some will develop into the placenta. At around day twelve, the embryo is twenty to thirty centimeters in length—a very thin, fragile bit of tissue. It is at this stage that each embryo occupies the place and space in the uterus and it will grow within the remaining 104 days of gestation. At this stage, the embryo histologically signals the mother of its presence so that the pregnancy may continue. The corpora lutea form and produce progesterone for about fourteen days after ovulation, regardless of the presence of embryos. There is no need for a signal before day twelve. When embryos are present at day twelve and provide an adequate signal, the corpora lutea persist, maintaining the secretion of progesterone that maintains the pregnancy and prevents recurring ovulation and a new estrus cycle. In the event of an inadequate signal (as the result of no embryos or too few), the corpora lutea regress, and a new ovulation occurs.

The pig is unique in that the proportion of the uterus that is occupied determines whether the signal is adequate. If half of the uterus is not occupied by embryos on day thirteen, the signal is inadequate, and the corpora lutea will regress, even though there may have been some live embryos in some segment of the uterus. The anatomy of the uterus of the rat and rabbit is such that each horn is entirely separate, and embryos cannot migrate between horns. In cows, sheep, and mice, intrauterine migration occurs infrequently. The embryos of the sheep and the cow signal the corpora lutea on the ovaries adjacent to the horns in which they are implanted. If an embryo is removed and placed in the opposite horn, the signal rarely goes from the uterine horn on one side to the ovary on the opposite side. The pregnancy will cease in that case in spite of the presence of an embryo. The uterus of the horse consists primarily of the body with no pronounced horns. Embryos of the horse do not migrate great distances and have only a local effect, influencing only the ovary on one side of the uterus.

The heart of the pig embryos begins to beat at about day sixteen. The uterus begins to expand at day eighteen, and by day thirty, the fetuses are about two centimeters long. The fetus is now surrounded by a round ball of fluid, the amnion. It will be floating in a zero-gravity environment for the next fifty days. The pig fetus grows roughly two centimeters every ten days until term. The first thirty days of gestation are critical for establishing systems and forming organs. It is during these embryonic stages that the embryo is very sensitive to toxins. The mother, the placenta, and the fetus all strive to protect the developing fetus from the harsh external environment.

Fetal Loss

Not all embryos and fetuses survive to term. For most species, only about 55 percent of the eggs finally end up as live fetuses. There are many potential causes for this prenatal loss. Some eggs are not fertilized because either the sperm or egg is faulty. Because the lives of an unfertilized egg and a sperm are both finite, limited to a matter of hours, the timing of the meeting of the sperm and egg at fertilization must be synchronized precisely, or a nonviable embryo will result. Even if fertilization occurs, the egg or sperm may have inherent chromosomal defects that produce a nonviable embryo. Any disruption of the rate of development of the embryo or in the rate of change in the uterus or composition of uterine milk will cause loss of the embryo. Synchronous, parallel development of the mother’s uterus and the embryo is absolutely essential for the survival of the embryo. Factors such as toxic chemicals, estrogens, and severe dietary changes can greatly affect the chances of survival. In some cases, the amounts of progesterone, estrogen, and other hormones essential for pregnancy are slightly abnormal. In species that bear large litters, the uterine space available to each fetus is not always equal, with the result that some fetuses do not have sufficient uterine resources for survival.

Not all embryos grow and implant within a few days of entering the uterus. The embryos of badgers, mink, lactating rats, seals, kangaroos, deer, marsupials, anteaters, armadillos, deer, and many other mammals are among those that may delay implantation in a process called embryonic diapause. When this temporary developmental pause occurs, the embryo develops to the early blastocyst stage (around eighty cells), and it remains dormant in this state until the mother deems conditions favorable to bear offspring. Temperature, lactation, food availability, captivity, and other stressors may trigger this pause. For example, when a lactating rat with delayed implantation weans the pups, the embryos resume growth. In mink and some other species, the ratio of light to dark each day influences the time of resumption of growth. The knowledge of this phenomenon goes back more than one hundred years, as indicated by the records of roe deer collected by the physician of a noble on a large estate. He had an opportunity to examine the uteri of roe deer killed for meat. He had noted the dates of mating but found no fetuses even after several months. This led to the discovery that the blastocyst’s development had been arrested for a prolonged period before resumption.

The Study of Gestation

The accumulation of knowledge on pregnancy and prenatal development has taken place over a long period. From the early superficial, gross observations of dead animals to the recent sophisticated and detailed techniques of observation of both mother and embryo or fetus, methods of exploring the changes that take place have developed. One procedure has its origin in antiquity. A cesarean section is a surgical procedure in which the fetus is brought out of the uterus through an incision in the abdominal wall and the uterus. (The term derives the name from the belief that Julius Caesar was delivered by that procedure.) Embryos can be removed very early and still survive. The ability to recover embryos and keep them alive outside the body for several days during the first six or seven days after fertilization has been a major step in the study of embryos. The culture fluid must have many characteristics similar to uterine milk to be compatible with living embryos. Temperature, the ratio of gases, the osmotic pressure of the fluid, and chemical composition must all be near those of the normal uterine environment. Each component may be modified slightly to achieve optimum livability at different stages of development and in different species. Embryos from several species may now be frozen and preserved for many years. This creates many possibilities for studies but also creates ethical and moral dilemmas.

The transfer of embryos between mothers of the same species has provided a means of separating the maternal genetic influence from the effect of the intrauterine environment on the fetus. Embryos from smaller breeds of rabbits grow larger than normal when transferred to a larger breed. Zebra foals have been born to horse mares as the result of transferring zebra embryos to the horse. The use of ultrasound to obtain an image of the fetus, the uterus, and surrounding tissue by noninvasive means has been very helpful. It is possible to get a frequent picture of the course of events in the uterus to monitor the development of the fetus. Nuclear magnetic resonance imaging can generate a picture of the uterus and its contents noninvasively. By nuclear magnetic resonancespectroscopy, chemical reactions can be measured in very small segments of the uterus and placenta. Optical systems inserted into the amniotic cavity with the fetus permit direct visualization of the fetus. Perfection of surgical techniques has permitted the insertion of cannulas into the blood vessels of experimental fetuses to monitor the concentration of hormones. The development of the brain of fetuses has been measured by the use of minute electrodes and cannulas placed in specific points.

The concentration of hormones circulating in the mother and fetus can be measured, often and with great precision and specificity, by radioimmunoassay of very small quantities of blood. These hormones change with different stages of gestation. The normal changes and concentrations have been determined for a wide variety of animals. An interesting aspect of the emerging picture of the various species studied is the great variety of mechanisms by which pregnancy exists. No two species have the same mechanism, even though they may appear to be very similar. As this rapidly growing area of knowledge expands, humans will be able to shed light on the inside of the uterus, which has been called one of the darkest places on Earth.

Fostering Optimal Pregnancies

Humankind has entered an era of unprecedented ability to understand the complexities of animal pregnancy. The efficiency of the animals related to human consumption—in the production of food, fiber, recreation, and companionship—depends largely on the efficiency of pregnancy. Among cows, horses, pigs, sheep, and goats, the proportion of mated females that conceive and bear young is less than 100 percent. The proportion of the fertilized eggs that develop into differentiated embryos is less than 100 percent. The proportion of embryos that develop into full-term fetuses born alive is less than 100 percent. Of those fetuses born alive, less than 100 percent survive more than a few days because of problems that had occurred prenatally. As an example, the runt of the litter often cannot compete successfully and perishes. Often, these animals were stunted in the uterus because of inadequate space or other resources, such as energy and gas exchange. Some of the inadequacies of resources may be avoided by proper prenatal care.

Avoiding adverse effects on embryos and fetuses of all species should be humanity’s aim; it may be possible to correct both maternal and fetal problems by judicious prenatal monitoring and treatment. A problem anticipated is half-solved. A sheep with twins needs different feeding and management from one with a single lamb. Prenatal monitoring can anticipate a problem, and treatment may prevent it.

Principal Terms

Corpus Luteum (pl. corpora lutea): The structure on the ovary that is formed from the follicle after the egg has been released; it secretes progesterone

Embryo: A fertilized egg as it undergoes divisions from one cell to several thousand cells, but before the individual is completely differentiated into a fetus

Estrogen: A hormone secreted by the ovary and placenta for development of the uterus

Fetus: A differentiated but undeveloped individual with organ systems usually identifiable as a member of a species

Ovary: The female gonad that is the source of eggs to be fertilized and hormones to maintain pregnancy

Oviduct: A narrow, hollow tube that takes the newly ovulated egg from the ovary, provides the site for fertilization, and transports the new embryo to the uterus.

Placenta: The tissue providing contact for the exchange of nutrients between the lining of the mother’s uterus and the blood supply from the fetus

Progesterone: The hormone essential for the maintenance of pregnancy that is secreted by the corpus luteum

Uterus: The hollow internal female organ that accommodates the embryo as it grows to term

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