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Reproductive Biology and Endocrinology

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Open Access 01-12-2018 | Research

Uterine Foxl2 regulates the adherence of the Trophectoderm cells to the endometrial epithelium

Authors: Michal Elbaz, Ron Hadas, Louise M. Bilezikjian, Eran Gershon

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

Abstract

Background

Forkhead Transcription Factor L2 (FOXL2) is a member of the forkhead family with important roles in reproduction. Recent studies showed that FOXL2 is expressed in human and bovine endometrium and that its levels fluctuate during pregnancy. In this study, we aimed at evaluating the expression and function of FOXL2 in embryo implantation.

Methods

Mouse uteri at different days of pregnancy were isolated and analyzed for the expression and localization of FOXL2. A lentiviral strategy was further employed to either knockdown or overexpress FOXL2 in non-receptive human endometrial AN3-CA cells and in receptive Ishikawa cells, respectively. These genetically modified cells were compared to cells infected with a control lentivirus to determine the function of FOXL2 in trophectoderm cells adherence to Endometrial Epithelium was associated with the expression of genes known to be involved in acquisition of uterine receptivity.

Results

We report that FOXL2 is expressed in both, the luminal epithelium and the myometrium of the mouse uterus and that its expression declines prior to implantation. We found that endometrial cells expressing low FOXL2 levels, either endogenous or genetically manipulated, were associated with a higher attachment rate of mouse blastocysts or human Jeg3 spheroids and mouse blastocysts. In accordance, low-FOXL2 levels were associated with changes in the expression level of components of the Wnt/Fzd and apoptotic pathways, both of which are involved in uterine receptivity. Furthermore, FOXL2 expression was inversely correlated with G-protein signaling protein 2 (Rgs2) and cytokine expression.

Conclusions

These results suggest that FOXL2 interferes with embryo attachment. Better understanding of the function of FOXL2 in the uterus would possibly suggest novel strategies for treatment of infertility attributed to repeated implantation failure.

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Title: Uterine Foxl2 regulates the adherence of the Trophectoderm cells to the endometrial epithelium
Authors: Michal Elbaz
Ron Hadas
Louise M. Bilezikjian
Eran Gershon
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-018-0329-y

At a glance: The STEP trials

Springer Medicine

Uterine Foxl2 regulates the adherence of the Trophectoderm cells to the endometrial epithelium

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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