Obesity and PCOS: The Effect of Metabolic Derangements on Endometrial Receptivity at the Time of Implantation

Abstract

Successful embryonic implantation is the result of a receptive endometrium, a functional embryo at the blastocyst stage and a synchronized dialog between maternal and embryonic tissues. Successful implantation requires the endometrium to undergo steroid-dependent change during each menstrual cycle, exhibiting a short period of embryonic receptivity known as the window of implantation. The term ''endometrial receptivity'' was introduced to define the state of the endometrium during the window of implantation. It refers to the ability of the endometrium to undergo changes that will allow the blastocyst to attach, penetrate, and induce localized changes in the endometrial stroma. These changes are metabolically demanding, and glucose metabolism has been proven to be important for the preparation of the endometrium for embryo implantation. Obesity and polycystic ovary syndrome (PCOS) represent 2 common metabolic disorders that are associated with subfertility. The aim of this review is to summarize the effect of obesity and PCOS on endometrial receptivity at the time of implantation. Focus will be on metabolic alterations that regulate decidualization, including glucose metabolism, hyperinsulinemia, and hyperandrogenism.

Lack of cyclical fluctuations of endometrial GLUT4 expression in women with polycystic ovary syndrome: Evidence for direct regulation of GLUT4 by steroid hormones

“…Because the proliferation, differentiation, secretion, and apoptosis of endometrial cells are controlled by steroid hormones [2] , and given the fact that glucose uptake and utilization play a crucial role in implantation, embryonic development, and pregnancy [5] , [6] , it remains to be determined how endometrial GLUT4 contributes to glucose metabolism in response to P4 stimulation under physiological conditions in vivo. On the other hand, the observation that decreased endometrial GLUT4 expression by P4 stimulation is surprising, especially because the endometria in PCOS patients tend to remain in a proliferative state due to the lack of counterbalance by P4 [44] .…”

“…The human endometrium includes epithelial cells, stromal cells, immune cells, and blood vessels [1] , and both epithelial and stromal cells are exquisitely sensitive to steroid hormone stimulation in women during the menstrual cycle [2] . In addition to estrogen and progesterone, human uterine fluid contains blood-derived glucose that is required for ATP synthesis [3] , [4] , and the link between glucose metabolism, implantation, embryonic development, and pregnancy has been recognized [5] , [6] . There is an increasing body of evidence indicating that glucose transporters (GLUTs) are responsible for the transport of glucose across the cell membrane and that they regulate glucose utilization in tissues and cells [5] .…”

Pre-pregnancy body mass index and time to pregnancy among couples pregnant within a year: A China cohort study

“…For example, obesity could cause ovulatory dysfunction, sex hormone disorders, and metabolic syndrome by increasing secretion of estrogen and leptin, and decreasing levels of gonadotropins and progestin [37,38]. Meanwhile, obesity might also be associated with injured endometrial receptivity [39], implantation [40], and organic diseases such as polycystic ovarian syndrome (PCOS) [41]. Finally, inflammation [42] and fatty acid toxicity [43], which occurs more frequently among obese women, could damage the eggs and impair functioning of the reproductive organs.…”

Emerging role for dysregulated decidualization in the genesis of preeclampsia

“…Several diseases have been reported to both impair decidualization and predispose to preeclampsia including polycystic ovarian syndrome [79–84], obesity [79, 80, 85, 86], diabetes mellitus [87–89], and endometriosis [90–92]. These comorbidities may exert their disruptive action on the endometrium through anomalous inflammation, exaggerated production of androgens, insulin, and homocysteine, as well as pathological epigenetic modifications [79, 91, 93–96]. Indeed, epigenetic dysregulation is another likely instigating factor, insofar as much of the normal biological process of decidualization is epigenetically regulated [97–103].…”