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

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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 αv and β3 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 β3 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.

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Acknowledgments

The authors thank Department of Science and Technology and Indian Council of Medical Research for financial assistance. Dr Nafisa Balasinor, Ms Reshama Gaonkar and Ms Shobha Sonawane are profusely thanked for their help in confocal microscopy. The authors also thank Dr Balasinor for the gift of antibodies against PCNA. Dr Srabani Mukherjee, Ms Gayatri Shinde and Ms Sushama are thanked for their assistance in flow cytometry. We appreciate Ms Ruchi Kakar for critically editing the manuscript. The help rendered by Mr M S Shinde and animal house facility is highly appreciated. SNJ also acknowledges Lady Tata Memorial Trust for providing her junior and senior research fellowships during the course of study.

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Correspondence to Geetanjali Sachdeva.

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Nimbkar-Joshi, S., Katkam, R.R., Chaudhari, U.K. et al. Endometrial epithelial cell modifications in response to embryonic signals in bonnet monkeys (Macaca radiata). Histochem Cell Biol 138, 289–304 (2012). https://doi.org/10.1007/s00418-012-0951-2

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