Uterine secretomics: a window on the maternal-embryo interface

Cheong, Ying; Boomsma, Carolien M.; Heijnen, Cobi J.; Macklon, Nick S.

doi:10.1016/j.fertnstert.2013.01.144

Cited by 53 publications

(44 citation statements)

References 58 publications

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“…Emerging evidence over the last decade in humans points to roles for uterine glands and their secretory products in uterine receptivity, blastocyst implantation, and postimplantation conceptus (embryo/fetus and associated extraembryonic membranes or placenta) growth and development during the first trimester (56,60,61). Although for many decades the secretions of glands have been hypothesized to play an essential role in sustaining the conceptus before implantation (62,63), their potential role in postimplantation development of the embryo and placenta in humans was largely ignored until recently (60,64). The human conceptus undertakes interstitial implantation beginning around day 7 postfertilization that is completed by day 10-12 (60,65).…”

Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

Kelleher

Wang

Pru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

120

164

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Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model. The uteri of adult FOXA2-deleted mice were morphologically normal and contained glands, whereas the uteri of neonatal FOXA2-deleted mice were completely aglandular. Notably, adult FOXA2-deleted mice are completely infertile because of defects in blastocyst implantation and stromal cell decidualization. Leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin, was not expressed during early pregnancy in adult FOXA2-deleted mice. Intriguingly, i.p. injections of LIF initiated blastocyst implantation in the uteri of both gland-containing and glandless adult FOXA2-deleted mice. Although pregnancy was rescued by LIF and was maintained to term in uterine gland-containing adult FOXA2-deleted mice, pregnancy failed by day 10 in neonatal FOXA2-deleted mice lacking uterine glands. These studies reveal a previously unrecognized role for FOXA2 in regulation of adult uterine function and fertility and provide original evidence that uterine glands and, by inference, their secretions play important roles in blastocyst implantation and stromal cell decidualization.T he uterus is comprised of two tissue compartments, the endometrium and the myometrium. The endometrium contains three cell types, luminal epithelium (LE), glandular epithelium (GE), and stroma. In mice, the uterus becomes receptive to blastocyst implantation on gestational day (GD) 4 (with the observation of a postcoital vaginal plug designated GD 0.5); it is prereceptive on GD 1-3, and by the afternoon of GD 5 it becomes nonreceptive (refractory) (1-3). Dynamic changes in ovarian estrogen and progesterone production act via the uterus to regulate uterine receptivity, blastocyst implantation, and stromal cell decidualization necessary for the establishment of pregnancy (4-6). The implantation process, which is initiated by the attachment of the blastocyst trophectoderm to the receptive LE, occurs before or right after midnight in the evening of GD 4 and becomes more prominent by the morning of GD 5. By GD 6, the trophectoderm begins to contact directly stromal cells that then begin to differentiate into decidual cells, which are required for successful pregnancy because they regulate placental development and local maternal immune responses (7,8).The infertility observed in leukemia inhibitory factor (Lif)-null mice and uterine gland-knockout (UGKO) mice and sheep established ...

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Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

Kelleher

Wang

Pru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

120

164

View full text Add to dashboard Cite

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“…4,5 Given the pervasiveness of this problem, many efforts have been made to study the receptivity of the endometrium for the blastocyst. 6,7 However, the molecular mechanism underlying the crosstalk between the embryo and endometrium remains unclear.…”

Section: Introductionmentioning

confidence: 99%

ATP mediates the interaction between human blastocyst and endometrium

Yang

et al. 2019

Cell Proliferation

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Objective Embryo implantation needs a reciprocal interaction between competent embryo and receptive endometrium. Adenosine triphosphate (ATP) produced by stressed or injured cells acts as an important signalling molecule. This study aims to investigate whether adenosine triphosphate (ATP) plays an important role in the dialogue of human blastocyst‐endometrium. Materials and methods The concentration of lactate was analysed in culture medium from human embryos collected from in vitro fertilization patients. Extracellular ATP was measured by ATP Bioluminescent Assay Kit. Ishikawa cells and T‐HESCs were treated with ATP, ATP receptor antagonist, ATP hydrolysis enzyme or inhibitors of ATP metabolic enzymes. The levels of gene expression were evaluated by real‐time PCR and immunoassay. Results We showed that injured human endometrial epithelial cells could rapidly release ATP into the extracellular environment as an important signalling molecule. In addition, blastocyst‐derived lactate induces the release of non‐lytic ATP from human endometrial receptive epithelial cells via connexins. Extracellular ATP stimulates the secretion of IL8 from epithelial cells to promote the process of in vitro decidualization. Extracellular ATP could also directly promote the decidualization of human endometrial stromal cells via P2Y‐purinoceptors. More importantly, the supernatants of injured epithelial cells clearly induce the decidualization of stromal cells in time‐dependent manner. Conclusion Our results suggest that ATP should play an important role in human blastocyst‐endometrium dialogue for the initiation of decidualization.

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“…But only about half of menstrual fluid is blood, and the rest is thought to be a transudate (Fraser et al, 2001). The composition of non-menstrual endometrial fluid includes plasma-derived proteins, and most notably, albumin (Cheong et al, 2013;Casslen and Nilsson, 1984). The transudate during menses may be similarly albumin-rich and thus containing PFAS, tightly bound to plasma-derived albumin.…”

Section: Discussionmentioning

confidence: 99%