Human early placental development: potential roles of the endometrial glands

Abstract

There is strong evidence that the endometrial glands play a key role in regulating placental development in many domestic species, but their contribution in the human has largely been ignored once implantation is complete. Here we re-evaluate their role during the first trimester. Connections between the glands and the intervillous space have been observed from day 17 post-conception through to the end of the first trimester. In the absence of a maternal arterial supply to the early placenta it is believed that the carbohydrate- and lipid-rich secretions represent an important source of nutrients during the first trimester, and possibly the beginning of the second trimester. The secretions also contain a variety of growth factors that may regulate placental morphogenesis since their receptors are present on villous and extravillous trophoblast, and villous endothelial cells. Other components of the secretions may modulate immune responses and trophoblast invasion at the materno-fetal interface. We speculate that lactogenic hormones secreted by decidual cells and the syncytiotrophoblast may act in concert with human chorionic gonadotropin to stimulate the secretory activity of glandular epithelial cells during the first trimester. There is circumstantial evidence, but as yet no conclusive proof, that deficient glandular activity is associated with pregnancy failure in the human.

Fig. 1

Diagrammatic representation of the relationship of the conceptus to the uterine glands during the first trimester. A) The blastocyst attaches and implants between openings of the uterine glands. The prevailing oxygen concentration will be low as the superficial decidua is oedematous and supplied by a capillary plexus arising from the spiral arteries, favouring trophoblast proliferation. B) As the conceptus enlarges the syncytiotrophoblast will invade into the superficial capillaries and the uterine glands, releasing the contents of both into the lacunae. EGF from the glands will stimulate trophoblast proliferation in the earliest stages, aiding development of the cytotrophoblastic shell. hCG and hPL from the syncytiotrophoblast, and prolactin from the decidual cells may in turn stimulate the glandular cells. C) As the conceptus enlarges the syncytiotrophoblast will encroach on the tips of the spiral arteries. It is essential that the cytotrophoblastic shell is well-formed by this stage, in order that sufficient endovascular extravillous trophoblast cells (EVT) are available to plug the spiral arteries beneath the conceptus. Incomplete plugging of the arteries in the periphery of the normal placenta is associated with early onset of the maternal circulation and villous regression to form the chorion laeve.

Fig. 2

Summary of the potential servomechanism by which the human conceptus may stimulate activity in the glandular epithelial cells to meet its requirements.