Abstract

BackgroundEmbryo implantation is a tightly regulated sequence of events regulated by ovarian steroids, estrogen and progesterone, and their downstream targets. Ovarian steroids regulate most of the genes involved in embryo implantation and pregnancy. However, some factors are not regulated by ovarian steroids, estrogen, progesterone, or both. Kruppel-like factor 5 (Klf5) is an example of an ovarian steroid–independent factor having a role in cellular proliferation, differentiation. The detailed expression profile of Klf5 during uterine receptivity and periimplantation has not been studied till now. In the present research work, an attempt was made to investigate the expression pattern of Klf5 in mice fetal-maternal tissue during periimplantation (day 4–day 8). The expressional and functional independence of Klf5 on the ovarian steroids was studied using estrogen and progesterone antagonist. The study was carried out in female Swiss albino mice of LACA strain during the periimplantation period. KLF5 was localized in the fetal-maternal tissues using the immunofluorescence technique in paraffin-embedded tissues. Ovarian steroid antagonists were administered subcutaneously from day 1 to day 3 of gestation, and the uterus was collected on the morning of day 4. Klf5 protein and mRNA levels were studied by western blot and quantitative real-time PCR (qPCR), respectively.ResultsKLF5 was localized in the embryo, uterine luminal epithelium, glandular epithelium, and proliferating stromal cells during periimplantation. In ovarian steroid antagonist–treated groups, KLF5 was localized in the luminal and glandular epithelium and stroma. Western blot and qPCR confirmed translation and transcription of KLF5 during the experimental period. The KLF5 protein level significantly increased on day 6, day 7, and day 8 when compared with day 4 (P < 0.05). The mRNA level of Klf5 increased significantly on day 7 and day 8 when compared with day 4 (P < 0.05). In ovarian steroid antagonist–treated groups, protein and mRNA corresponding to Klf5 were observed. From this finding, it can be assumed that Klf5 may be a steroid-independent factor expressed during uterine receptivity.ConclusionSpatiotemporal KLF5 expression in fetal-maternal tissue was observed during the experimental period. The results suggest that Klf5 is an ovarian steroid–independent factor that may play a pivotal role in implantation, decidualization, and embryogenesis.

Highlights

  • Embryo implantation is a tightly regulated sequence of events regulated by ovarian steroids, estrogen and progesterone, and their downstream targets

  • Several uterine glands of circular and elongated shape embedded in the stromal cell layer were observed in the uterine section on Day 4 (D4) of pregnancy

  • Moderate intensity of Immunostaining signal was reported in the luminal epithelium (LE) on D4 of

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Summary

Introduction

Embryo implantation is a tightly regulated sequence of events regulated by ovarian steroids, estrogen and progesterone, and their downstream targets. The luminal epithelial cells in contact with implanting blastocyst undergo apoptosis or entosis, permitting the motile blastocyst trophectoderm to come in contact with stromal cells inducing decidualization [4,5,6,7] This critical interaction of fetal-maternal tissue is associated with uterine receptivity and window formation, which are the primary requirement of uterine function for successful embryo implantation and its growth [8, 9]. Ovarian estrogen secretion superimposed with high progesterone secretion from corpora lutea on day 4 of pregnancy leads to extensive stromal cell proliferation, luminal epithelial differentiation, and glandular secretion rendering the uterus receptive for implantation [12,13,14]

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