Endometrial epithelial cell modifications in response to embryonic signals in bonnet monkeys (Macaca radiata)

Abstract

The present investigation reports embryo-induced modifications in the epithelial cells of the endometrium in a primate species. In vivo, epithelial cell response to the embryonic signals was assessed at the embryo attachment stage in the gestational uterus of bonnet monkeys (Macaca radiata) and in vitro response was investigated by treating human endometrial epithelial cell line (Ishikawa) with human embryo conditioned media (CM). Endometrial epithelial (EE) cells at the embryo attachment stage in bonnet monkeys revealed higher proliferation accompanied by significant up regulation (p < 0.05) in the expression of estrogen receptor (ER)α and down regulation (p < 0.05) in ERβ expression. Further gestational EE cells showed higher (p < 0.001) expression of mucin-1, except in the embryo attachment site. Also, observed were significantly higher expression (p < 0.05) and altered cytoplasmic distribution of α(v) and β(3) integrins, when compared to non-pregnant animals. In pregnant animals, the embryo attachment zone showed differential expression of immunoreactive integrins as compared to the non-attachment zone. This suggested the role of embryo secreted factors in modulation of the epithelial cell profile. In vitro studies partially supported this assumption. Significantly higher proliferation (p < 0.05), as well as increased expression of ERα, integrin β(3) and mucin-1 (p < 0.05) were observed in Ishikawa cells, on stimulation with CM. Taken together, these results indicated the proliferation and modulation in the expression of estrogen receptors and cell adhesion molecules in the EE cells; at the embryo attachment stage in bonnet monkeys. Further it is likely that embryo secreted factors contribute to some of these modifications in EE cells. This report is the first account of discrete cellular events, which occur in the uterine epithelium, at the embryo attachment stage in a primate species.

Oviductal glycoprotein 1 (OVGP1) is expressed by endometrial epithelium that regulates receptivity and trophoblast adhesion

“…However, notwithstanding this notion, we and others have demonstrated an extensive remodeling of the endometrium Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10815-018-1231-4) contains supplementary material, which is available to authorized users. by the embryo at the time of implantation [3,[12][13][14][15]. It has been shown [16,17] that the endometrial remodeling at the time of implantation is mediated by embryo-derived soluble factors like chorionic gonadotropin (CG) and interleukin 1β (IL1β).…”

Utilization of cargo from extra cellular vesicles as a biomarker for endometrial receptivity for enhancement of implantation success during attempted IVF/ICSI- a short communication

“…Thus in future they need to do aspiration of endometrium at the time of frozen embryo transfer inclusive of evaluation of the embryos for euploidy/aneuploidy to have the full picture besides establishing ecvs with sncRNAs having the probility of getting used as biomarkers for anticipation of implantation along with successas biomarkers. 11…”

“…Various studies have illustrated that the embryo further liberates ECV's which changes the endometrium, thus possessing influence on receptiveness. 10,11 Trying to evaluate the alterations in expression patterns without considering what the embryos contribution might keep the partial picture in dark. Despite, the precautions taken by Li, etal., 8 their strategy of evaluation of the query with regards to a significant doubt about ECV as well as their association with endometrial receptivity.…”

Modulation of endometrial E-Cadherin and N-Cadherin by ovarian steroids and embryonic stimuli

“…Thus it appears that in vivo, there could be additional factors required to induce EMT at the time of embryo invasion. Since embryo-derived factors alter the expression of genes in the luminal epithelium (Nimbkar-Joshi et al, 2012;Ashary et al, 2018Ashary et al, , 2020Laheri et al, 2018), it is tempting to propose the EMT occurring in luminal epithelium at the time of implantation could be due to embryo driven factors. Further studies will be required to address this hypothesis.…”

“…Extensive modifications occur in the endometrium at this time in response to the midcycle estrogen surge and embryonic factors (Nimbkar-Joshi et al, 2012;Zhang et al, 2013;Strug et al, 2016;Kurian and Modi, 2019;Mishra et al, 2021). In response to embryonic stimuli, the luminal epithelial cells lose their polarity, proliferate and there is an altered expression of several molecules required for embryo apposition and implantation (Nimbkar-Joshi et al, 2012;Modi and Bhartiya, 2015;Ashary et al, 2018;Laheri et al, 2018;Ochoa-Bernal and Fazleabas, 2020). Controversies exist on the pattern of E-Cad expression in the endometrial epithelium at the time of embryo implantation.…”