Implantation in the Baboon: Endometrial Responses

Abstract

Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation. Changes that occur within this window of receptivity and immediately following implantation can be divided into three distinct phases. The first phase, regulated by estrogen and progesterone, is characterized primarily by changes in both the luminal and glandular epithelial cells in preparation for blastocyst apposition and attachment. The second phase is the further modulation of these steroid induced changes in both epithelial and stromal cells by embryonic signals. The final phase is associated with trophoblast invasion and the remodeling of the endometrial stromal compartment. During the initial phase, the actions of estrogen and progesterone are dependent on the presence of specific receptors. Estrogen up-regulates both its own receptor (ER) and the progesterone receptor (PR), while progesterone down-regulates this expression pattern. However, the pattern of progesterone-induced down-regulation of ER and PR is confined to the epithelial cells and demonstrates a gradient effect from the functionalis to the basalis. What is most intriguing is that the loss of epithelial PR is closely correlated with the establishment of uterine receptivity. Coincident with the changes in ER and PR expression, epithelial cells undergo alterations in their cytoskeletal architecture and secretory profile. These changes can be counteracted by PR antagonist treatment during the luteal phase. Although estrogen and progesterone play a critical role in establishing the initial phase of uterine receptivity, it is becoming increasingly evident that the embryo induces functional receptivity in ruminants and rodents. In our studies in the primate, we demonstrate that chorionic gonadotrophin when infused in a manner that mimics blastocyst transit, has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial plaques are evident. The glandular epithelium responds by inducing transcriptional and post-translational modifications in the major secretory product, glycodelin. The stromal fibroblasts initiate their differentiation process into a decidual phenotype and are characterized by the expression of actin filaments. In phase three, blastocyst attachment to the surface epithelium and subsequent implantation is associated with local remodeling of the maternal stroma, smooth muscle, and endothelium of the blood vessels by the trophoblast. In addition, there is a gradual diminution of the epithelial plaques on the luminal surface although the glandular epithelium remains highly secretory. The most dramatic effect is on the stromal fibroblasts, which in response to embryonic stimuli, differentiate into decidual cells, the major cell type of the gestational endometrium. This differentiation is characterized by the expression of insulin-like growth factor binding protein-1 (IGFBP-1) in these cells. The cytokine IL-1 beta is one possible embryonic signal. COX-2 is t...

Fetal-Maternal Conflict, Trophoblast Invasion, Preeclampsia, and the Red Queen

“…It is not certain, however, how far decidualization in different nonhuman primates develops spontaneously during each menstrual cycle, as in the human, or is induced by an implanting blastocyst, as happens in rodents. For example, in the baboon, there is good evidence that decidualization is indeed induced by the implanting blastocyst (38). Such induction process fits nicely in our game of chess model for maternal-fetal interaction.…”

Epithelial Human Chorionic Gonadotropin Is Expressed and Produced in Human Secretory Endometrium During the Normal Menstrual Cycle1

“…The effect of hCG on human secretory endometrium promotes morphological and functional differentiation of stromal cells into decidual cells [41,42]. However, even in the absence of implantation, predecidual reactions of stromal fibroblast cell transformation leading to epithelial gland cell hyperplasia (including plaque formation in the luminal epithelium) occur in human secretory endometrium, while this predecidual cell transformation is absent during the normal estrogen-and progesterone-primed menstrual cycle of nonhuman primates [4,44,45]. Subsequent exogenous hCG administration also induces predecidual transformation.…”

Differential Expression of Genes in the Endometrium at Implantation: Upregulation of a Novel Member of the E2 Class of Ubiquitin-Conjugating Enzymes1

“…For example, there is a dramatic loss in detectable progesterone receptors in the luminal epithelial cells during implantation in multiple species [57,58]. In addition, there is a large down-regulation in cytokeratin 18 involved in the cytoskeletal reorganization of these cells during this process [9].…”