Uterine and placental factors regulating conceptus growth in domestic animals.

All mammalian uteri contain endometrial glands that synthesize or transport and secrete substances essential for survival and development of the conceptus (embryo/fetus and associated extraembryonic membranes). The ovine uterine gland knockout ewe model supports a primary role for endometrial glands and, by default, their secretions as essential for conceptus survival and development during the peri-implantation period of pregnancy. Endometrial adenogenesis, the process whereby glands develop in the uterus, is primarily a postnatal event in domestic and laboratory animals, as well as in humans. Endometrial adenogenesis involves differentiation and budding of glandular epithelium from lumenal epithelium, followed by invagination and extensive tubular coiling and branching morphogenesis throughout uterine stroma to the myometrium. In sheep, pituitary prolactin acting on prolactin receptors expressed by uterine glandular epithelium regulates endometrial adenogenesis. In contrast, expression and functional activation of estrogen receptor alpha in the uterus is a primary regulator of endometrial adenogenesis in the pig. In adult sheep and pigs, extensive endometrial gland hyperplasia and hypertrophy occur during gestation, presumably to provide increasing histotrophic support for conceptus growth and development. A servomechanism has been proposed in sheep and pigs to regulate endometrial gland development and differentiated function during pregnancy that involves sequential actions of ovarian steroid hormones, pregnancy recognition signals, and lactogenic hormones from the pituitary and/or placenta. The fact that disruption of uterine development during critical organizational periods can alter the functional capacity and embryotrophic potential of the adult uterus reinforces the importance of understanding uterine developmental biology. Defects in endometrial gland morphogenesis during uterine growth and development may cause the unexplained, high rates of peri-implantation embryonic loss in domestic animals and humans. Knowledge of the basic mechanisms regulating uterine development is expected to suggest means to increase uterine capacity, litter size, and neonatal survival, as well as ameliorate certain types of infertility.