Developmental biology of uterine glands

All mammalian uteri contain endometrial glands that synthesize or transport and secrete substances essential for survival and development of the conce ptus (embryo/fetus and associated extraembryonic membranes). In rodents, ut erine secretory products of the endometrial glands are unequivocally requir ed for establishment of uterine receptivity and conceptus implantation. Ana lyses of the ovine uterine gland knockout model support a primary role for endometrial glands and, by default, their secretions in peri-im plantation conceptus survival and development. Uterine adenogenesis is the process whe reby endometrial glands develop. in humans, this process begins in the fetu s, continues postnatally, and is completed during puberty. In contrast, end ometrial adenogenesis is primarily a postnatal event in sheep, pigs, and ro dents. Typically, endometrial adenogenesis involves differentiation and bud ding of glandular epithelium from luminal epithelium, followed by invaginat ion and extensive tubular coiling and branching morphogenesis throughout th e uterine stroma to the myometrium. This process requires site-specific alt erations in cell proliferation and extracellular matrix (ECM) remodeling as well as paracrine cell-cell and cell-ECM interactions that support the act ions of specific hormones and growth factors. Studies of uterine developmen t in neonatal ungulates implicate prolactin, estradiol-17 beta, and their r eceptors in mechanisms regulating endometrial adenogenesis. These same horm ones appear to regulate endometrial gland morphogenesis in menstruating pri mates and humans during reconstruction of the functionalis from the basalis endometrium after menses. In sheep and pigs, extensive endometrial gland h yperplasia and hypertrophy occur during gestation, presumably to provide in creasing histotrophic support for conceptus growth and development. In the rabbit, sheep, and pig, a servomechanism is proposed to regulate endometria l gland development and differentiated function during pregnancy that invol ves sequential actions of ovarian steroid hormones, pregnancy recognition s ignals, and lactogenic hormones from the pituitary or placenta. That disrup tion of uterine development during critical organizational periods can alte r the functional capacity and embryotrophic potential of the adult uterus r einforces the importance of understanding the developmental biology of uter ine glands. Unexplained high rates of peri-implantation embryonic loss in h umans and livestock may reflect defects in endometrial gland morphogenesis due to genetic errors, epigenetic influences of endocrine disruptors, and p athological lesions.