Embryo-induced alterations in the molecular phenotype of primate endometrium

Reproductive biomedicine has made significant advances in the area of assisted reproductive technologies in the last two and half decades. However, embryo implantation remains a major obstacle in securing high pregnancy rates. Various non-human primate models including rhesus, marmoset and baboon have been employed to elucidate in vivo mechanisms underlying the uterine events that initiate, sustain and complete implantation. This review collates the information available on the molecular profile of gestational endometrium in primates. Collectively, these studies reveal dynamic spatio-temporal changes in the expression of cytokines, growth factors, cell-adhesion molecules, cytoskeleton elements and other factors in the endometrium during the post-implantation phase of pregnancy. Considering that the endometrial events during the pre-implantation stages of pregnancy may dictate implantation success, we have developed a bonnet monkey (Macaca radiata) model where pregnancy can be detected at the pre-implantation stage. Using this model, we investigated some of the endometrial events that occur before the completion of implantation. Remarkable changes were observed in endometrial expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha), as well as expression of immunosuppressive factors such as transforming growth factor beta-2 (TGFbeta2), interleukin-6 (IL-6) and placental protein-14 (PP-14), even before the embryo starts invading the endometrium. This highlights the super-imposition of endometrial receptivity by embryonic stimuli, marked by differential expression and/or localization of the factors that regulate endometrial transformation for embryo survival, growth and development.