Progesterone, be it of either ovarian or placental origin, is critical for the establishment and maintenance of pregnancy. Progesterone acts to assure uterine quiescence by inhibiting the propagation of action potentials within the myometrium. It also increases secretory activity of the endometrium (histotrophe - nutrition for the developing embryo until placentation is complete) and causes solidification of cervical mucus (sealing off the uterine environment from external contaminants).
Although it is commonly believed that estrous behavior completely ceases during pregnancy, this is not the case. Anovulatory heats have been observed in domestic ruminants and several species of laboratory animal. Circulatory levels of estrogens in excess of those needed to cause psychological estrus in nonpregnant animals are generally achieved during pregnancy.
Rescue of the CL. Steroidogenic function of the CL is extended beyond that characteristic of the luteal phase of an infertile cycle in most mammals (excluding marsupials and some carnivores). The CL provides the source of supportive progesterone necessary in early gestation. Therefore, the CL must be rescued from regression in the pregnant state. Not surprisingly, the conceptus plays an active part in this aspect of maternal recognition of pregnancy. The nature of the embryonic signal and mechanisms of maintenance of luteal activity are only partially understood. Each species realizes this feat by somewhat different means.
In primates the luteotropic/antiluteolytic effect of gonadotropic hormone derived from syncytiotrophoblastic cells prevents demise of the CL. Human choriogonadotropin is detectable in the blood at implantation. Levels rise rapidly to peak at about nine weeks, and then gradually fall to relatively low levels for the remainder of pregnancy. Nausea and vomiting affect over one-half of all women during the first trimester of pregnancy. Symptoms are most prevalent upon awakening and are triggered by sensitivities to the smell/taste of certain foods (an adaptation that protects the conceptus from food-borne toxins that might otherwise be ingested by the mother?). This condition closely parallels the elevation in circulatory concentrations of hCG (the root cause of pregnancy sickness remains unknown - estrogen, hypoglycemia, bilirubin?). There is a slight increase in hCG after 34 weeks.
Estrogens secreted by porcine embryos cause a decrease in the amount of PGF2a released from the endometrium into the uterine venous system, thus preventing luteolysis. Follicular estrogens are necessary to support function of CL in rabbits, but are not the primary catalyst responsible for prolongation of luteal activity during pregnancy. The placenta is involved in inhibition of uterine production of PGF2a in rabbits.
Unique IFNa-like (tau) proteins originating from ovine and bovine conceptuses that are capable of extending luteal lifespan have recently been isolated (trophoblast protein-1). These molecules can alter the pattern of arachidonate metabolism by the uterus in favor of luteotropic/antiluteolytic prostaglandins (PGE2, PGI2). The effect of the gravid uterine horn on maintenance of luteal function is exerted locally (ie., through the utero-ovarian vascular pathway).
The story of prolongation of luteal function during pregnancy seems even more complex in certain other species. The rat, for example, relies sequentially on several hormones, namely prolactin, LH, and a placental luteotropin. The mating stimulus (fertile or infertile) activates a neural pathway leading to circadian surges of prolactin. One surge occurs during the day (diurnal), the other at night (nocturnal). These surges continue through Day 11. Prolactin counteracts the luteolytic effect of PGF2a and sensitizes CL to the luteotropic action of LH. A placental luteotropin (placental lactogen or a chorionic gonadotropin) is produced thereafter.
The pregnant mare presents a peculiar situation in which the ovulatory CL is rescued from regression, but then begins to regress, and is replaced by accessory luteal structures. The primary CL is unable to provide sustained progestational support of early pregnancy. Growth and ovulation/luteinization of follicles, producing secondary CL, is caused by PMSG. Equine choriogonadotropin begins to increase in plasma about the time of placental attachment, peaks and plateaus between Days 60 and 80, then declines to baseline by Day 120. Luteal activity wanes again midway through gestation. Formation of secondary CL has also been reported in mink, deer, and elephants.
Anterior pituitary/ovarian requirements. As pregnancy proceeds, the placenta produces increasing amounts of progesterone. The ovaries, and luteotropic support derived from the anterior pituitary gland, are usually not required to maintain pregnancy beyond the half-way point (ie., animals will not abort if ovariectomized or hypophysectomized during the second half of gestation). Not so for the rabbit, dog or pig, who command ovarian/pituitary support throughout gestation. Placenta of these species have a low capacity for production of progesterone.
Pseudopregnancy. An infertile mating (or related physical stimulus) leads to prolongation of the luteal phase in several spontaneous ovulators. Most rodents become pseudopregnant as a direct neural response to copulation. Induced ovulators and dogs become spontaneously pseudopregnant upon ovulation. As is the case with unmated cycles, lengths of pseudopregnancy (Table 5-13) are usually shorter than that of pregnancy (eg., rat: estrous cycle [4 days] < pseudopregnancy [12 days] < pseudopregnancy with DCR [18 days] < pregnancy [22 days] < pregnancy with diapause [40 days]). Lengths of pseudopregnancy and pregnancy are nearly equal in dogs and mink (thus, there is no necessity in these animals for active rescue of the CL by the conceptus). Farm animals and primates do not exhibit a natural pseudopregnancy (eg., it can be experimentally-induced in pigs by treatment with estrogen).