Molecular mechanisms of embryonic implantation in mammals: Lessons from the gene manipulation of mice

Abstract

BackgroundHuman infertility has become a serious and social issue all over the world, especially in developed countries. Numerous types of assisted reproductive technology have been developed and are widely used to treat infertility. However, pregnancy outcomes require further improvement. It is essential to understand the cross‐talk between the uterus (mother) and the embryo (fetus) in pregnancy, which is a very complicated event.MethodsThe mammalian uterus requires many physiological and morphological changes for pregnancy‐associated events, including implantation, decidualization, placentation, and parturition, to occur. Here is discussed recent advances in the knowledge of the molecular mechanisms underlying these reproductive events — in particular, embryonic implantation and decidualization — based on original and review articles.Main findings (Results)In mice, embryonic implantation and decidualization are regulated by two steroid hormones: estrogen and progesterone. Along with these hormones, cytokines, cell‐cycle regulators, growth factors, and transcription factors have essential roles in implantation and decidualization in mice.ConclusionRecent studies using the gene manipulation of mice have given considerable insight into the molecular mechanisms underlying embryonic implantation and decidualization. However, as most of the findings are based on mice, comparative research using different mammalian species will be useful for a better understanding of the species‐dependent differences that are associated with reproductive events, including embryonic implantation.

The ameliorating effects of Bushen Tiaoxue Granules and Kunling Wan on impaired angiogenesis and endometrial receptivity in rats following controlled ovarian hyperstimulation

“…20 The binding of estrogen and progesterone with their nuclear receptors ER and PR in the uterus promotes the production of VEGF, 56 which is a critical event for eliciting the temporal functions in mammalian angiogenesis and uterine receptivity. 16 In mice, deletion of ERα leads to reproductive phenotypic defects. 16 Other studies demonstrated that the PRKO mice that exhibit hyperplastic uteri are non-receptive to embryo implantation.…”

“…16 In mice, deletion of ERα leads to reproductive phenotypic defects. 16 Other studies demonstrated that the PRKO mice that exhibit hyperplastic uteri are non-receptive to embryo implantation. 40 In the present study, we found decreased expression of ERα, ERβ, and PR in the endometrium induced by COH, in consistence with the result from others.…”

“…12 Controlled ovarian hyperstimulation also results in induction of endometrial pathological changes, appearing lumen stenosis, planting window in advance, vascular dysfunction, and dyssynchronous glandular and stromal development 13,14 which are harmful to endometrial receptivity. 16 Previous results revealed that receptive state in the mouse uterus depends on LIF, which activates Janus kinase-signal transducer and activator of transcription 3 pathway and thus affects a cascade of events including angiogenesis therefore engaging in embryo implantation. 15 Estrogen and progesterone binding to ER and PR in the endometrium can produce on-time functions in the endometrial receptivity.…”

“…15 Estrogen and progesterone binding to ER and PR in the endometrium can produce on-time functions in the endometrial receptivity. 16 Previous results revealed that receptive state in the mouse uterus depends on LIF, which activates Janus kinase-signal transducer and activator of transcription 3 pathway and thus affects a cascade of events including angiogenesis therefore engaging in embryo implantation. [17][18][19] Studies have identified that vascular remodeling is fundamental at the maternal-fetal interface and LPA3 participates in the process of vascularization.…”

Progesterone governs endometrial proliferation-differentiation switching and blastocyst implantation

“…A blastocyst attaches to the receptive uterine luminal epithelium to start pregnancy. Then, the blastocyst invades into the endometrial stroma under the epithelium, and the stroma becomes decidua, which supports growth and survival of blastocyst [1][2][3][4][5][6][7]. Because it is estimated that implantation failure causes 75% of unsuccessful conceptions [8], it should be an obligatory mission to elucidate the mechanism and solutions of implantation failure.…”