Spatiotemporal expression and regulation of FoxO1 in mouse uterus during peri-implantation period.

Dileyra Adiguzel,Nilay Kuscu,Sinan Ozkavukcu,Pinar Sahin,Ciler Celik-Ozenci,Nayce Ilayda Bektas,Sachiko Matsuzaki

doi:10.1371/journal.pone.0216814

Abstract

Recent studies indicate that FoxO1 has roles in female reproductive system, especially in maternal endometrium. Although various cellular aspects and molecular pathways have been identified, the exact molecular characteristics of embryo implantation are still not completely understood. In this study, we aimed to investigate uterine expression and regulation of FoxO1 during peri-implantation period in mice. Experimental mouse models including, normal pregnancy, pseudopregnancy, artificial decidualization, and delayed implantation and activation were performed. Our results showed that FoxO1 expression was spatiotemporal in mouse endometrial tissue throughout peri-implantation period and its expression was significantly upregulated in luminal and glandular epithelium at the time of implantation. Moreover, on day 5 morning (09:00 AM) of pregnancy, expression of FoxO1 was cytoplasmic in endometrial luminal epithelial cells where embryo homing takes place. With progressing time on day 5 evening (19:00 PM) of pregnancy FoxO1 expression was nuclear in luminal epithelium at implantation site. Pseudopregnancy and artificial decidualization models indicated that FoxO1 expression was regulated by pregnancy hormones. Delayed implantation and activation model indicated that FoxO1 expression at the time of implantation is dependent upon activation status of blastocyst due to E2 induction and uterine sensitivity to implantation. In conclusion, our findings highlight a perspective for FoxO1 expression and regulation in mouse uterus during peri-implantation period indicating that its expression is regulated by implanting embryo and pregnancy hormones.

Highlights

Implantation is one of the crucial steps to successful pregnancy and requires reciprocal molecular dialog between the blastocyst and maternal endometrium [1,2,3,4,5,6]
Since timely expression of various molecules in endometrium is important for successful embryo implantation, we investigated Forkhead box O1 (FoxO1) expression at different time points throughout the window of implantation
We found that FoxO1 expression became apparent firstly in the cytoplasm of endometrial epithelial and glandular cells on early D4 (09:00 hr) and its expression was translocated to the nuclei of endometrial epithelial and glandular cells on late D4 (19:00 hr) as the uterus gains a receptive status for blastocyst attachment

Summary

Introduction

Implantation is one of the crucial steps to successful pregnancy and requires reciprocal molecular dialog between the blastocyst and maternal endometrium [1,2,3,4,5,6]. Ovarian estrogen and progesterone hormones that improve blastocyst competency and uterine receptivity primarily orchestrate this molecular dialog. Namely the ‘‘window of implantation”, is a restricted period that describes the receptive state of the uterus is suitable for embryo implantation [2,3, 7,8,9,10]. FoxO1 expression and regulation in mouse uterus study design, data collection and analysis, decision to publish, or preparation of the manuscript

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Conclusion