Biological roles of uterine glands in pregnancy

Abstract

All mammalian uteri contain glands in the endometrium that synthesize or transport and secrete substances essential for survival and development of the conceptus (embryo/fetus and associated extraembryonic membranes). This review summarizes information related to the biological roles of uterine glands and their secretions in blastocyst/conceptus survival and implantation, uterine receptivity, and stromal cell decidualization in humans and animal models. The infertility and recurrent pregnancy loss observed in the ovine uterine gland knockout (UGKO) model unequivocally supports a primary role for uterine glands and, by inference, their secretions present in uterine luminal fluid in survival and development of the conceptus. Further, studies with mutant and progesterone-induced UGKO mice found that uterine glands and their secretions are required for establishment of uterine receptivity and blastocyst implantation as well as stromal cell decidualization. Similarly in humans, uterine glands and their secretory products are likely critical regulators of blastocyst implantation, uterine receptivity, and conceptus growth and development during the first trimester. Circumstantial evidence suggests that deficient glandular activity may be a causative factor in pregnancy failure and complications in humans. Thus, an increased understanding of uterine gland biology is important for diagnosis, prevention, and treatment of fertility and pregnancy problems in mammals.

Figure 1

Hypothesis on the biological roles of uterine glands in blastocyst activation, uterine receptivity to blastocyst implantation, and stromal cell decidualization during pregnancy in mice. See text for detailed description of hypotheses and supporting data.

Figure 2

Schematic illustrating the relationship of the conceptus to the uterine glands during the first trimester of pregnancy in humans. A) The blastocyst attaches to the luminal epithelium and then implants into the superficial functionalis endometrium between the openings of the uterine glands. B) The implanted conceptus begins to grow and the syncytiotrophoblast invades into the superficial capillaries as well as the uterine glands, releasing the contents of both into the lacunae that will form the intervillous spaces. C) As the conceptus enlarges, the syncytiotrophoblast begins to reach the tips of the spiral arteries of the endometrium. It is essential that the cytotrophoblastic shell is fully developed by this stage in order that sufficient endovascular extravillous trophoblast cells (EVT) are available to plug the spiral arteries near the conceptus. Complete plugging of the arteries in the periphery of the normal placenta is necessary to allow the EVT to remodel them prior to the onset of maternal circulation at the end of the first trimester. Drawn by Carolyn Allen and adapted from Burton and coworkers.

Figure 3

Hypothesis on the interrelationships of the ovarian corpus luteum, conceptus trophoblast, uterine glands, and decidual cells during early pregnancy in humans. See text for detailed description of hypotheses and supporting data. Adapted from Burton and coworkers.