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

PLoS One. 2019 May 23;14(5):e0216814. doi: 10.1371/journal.pone.0216814. eCollection 2019.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Decidua / metabolism*
  • Embryo Implantation, Delayed / physiology*
  • Female
  • Forkhead Box Protein O1 / biosynthesis*
  • Gene Expression Regulation / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Pregnancy / physiology*
  • Pseudopregnancy / metabolism*

Substances

  • Forkhead Box Protein O1
  • Foxo1 protein, mouse

Grants and funding

This project has been supported by Scientific and Technological Research Council of Turkey (TUBITAK) with grant number SBAG-215S868 and by Akdeniz University Scientific Research Projects Unit with grant number TYL-2015-994 to CC-O. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.