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Journal of Ovarian Research

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Open Access 01-12-2018 | Research

Gonadotropin and steroid hormones regulate pluripotent very small embryonic-like stem cells in adult mouse uterine endometrium

Authors: Kreema James, Deepa Bhartiya, Ranita Ganguly, Ankita Kaushik, Kavita Gala, Pushpa Singh, S. M. Metkari

Published in: Journal of Ovarian Research | Issue 1/2018

Abstract

Background

Very small embryonic-like stem cells (VSELs) exist in adult organs, express pluripotent markers and have the ability to differentiate into three germ layers in vitro. Testicular, ovarian and hematopoietic stem/progenitor cells express receptors for follicle stimulating (FSH) and ovarian hormones and are activated by them to undergo proliferation/differentiation. VSELs exist in mouse uterus and are regulated by physiological dose of estradiol (E) & progesterone (P) during endometrial growth, differentiation and regeneration/remodeling. In the present study, effects of daily administration of E (2 μg/day), P (1 mg/Kg/day) or FSH (5 IU/day) for 7 days on the endometrium and stem/progenitor cells was studied in bilaterally ovariectomized mice.

Results

E treatment resulted in hypertrophy whereas P resulted in hyperplasia and overcrowding of epithelial cells. FSH also directly stimulated the endometrial cells. Nuclear OCT-4A positive VSELs were visualized in ovariectomized (atrophied) endometrium and cytoplasmic OCT-4B positive epithelial, stromal and endothelial cells were observed after treatment. FSH treated uterine tissue showed presence of 4 alternately spliced FSHR isoforms by Western blotting. 3–5 μm VSELs with a surface phenotype of LIN-/CD45-/SCA-1+ were enumerated by flow cytometry and were found to express ER, PR, FSHR1 and FSHR3 by RT-PCR analysis. Differential effects of treatment were observed on pluripotent (Oct4A, Sox2, Nanog), progenitors (Oct-4, Sca-1), primordial germ cells (Stella, Fragilis) and proliferation (Pcna) specific transcripts by qRT-PCR analysis. FSH and P (rather than E) exerted profound, direct stimulatory effects on uterine VSELs. Asymmetric, symmetric divisions and clonal expansion of stem/progenitor cells was confirmed by co-expression of OCT-4 and NUMB.

Conclusions

Results confirm presence of VSELs and their regulation by circulatory hormones in mouse uterus. Stem cell activation was more prominent after P and FSH compared to E treatment. The results question whether epithelial cells proliferation is regulated by paracrine influence of stromal cells or due to direct action of hormones on stem cells. VSELs expressing nuclear OCT-4A are the most primitive and pluripotent stem cells, undergo asymmetric cell division to self-renew and differentiate into epithelial, stromal and endothelial cells with cytoplasmic OCT-4B. Role of follicle stimulating and steroid hormones on the stem cells needs to be studied in various uterine pathologies.

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Title: Gonadotropin and steroid hormones regulate pluripotent very small embryonic-like stem cells in adult mouse uterine endometrium
Authors: Kreema James
Deepa Bhartiya
Ranita Ganguly
Ankita Kaushik
Kavita Gala
Pushpa Singh
S. M. Metkari
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2018
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-018-0454-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Gonadotropin and steroid hormones regulate pluripotent very small embryonic-like stem cells in adult mouse uterine endometrium

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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