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Journal of Ovarian Research

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Open Access 01-12-2013 | Research

RETRACTED ARTICLE: Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3

Authors: Hiren Patel, Deepa Bhartiya, Seema Parte, Pranesh Gunjal, Snehal Yedurkar, Mithun Bhatt

Published in: Journal of Ovarian Research | Issue 1/2013

Abstract

Background

We have earlier reported that follicle stimulating hormone (FSH) modulates ovarian stem cells which include pluripotent, very small embryonic-like stem cells (VSELs) and their immediate descendants ‘progenitors’ termed ovarian germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium (OSE). FSH may exert pleiotropic actions through its alternatively spliced receptor isoforms. Four isoforms of FSH receptors (FSHR) are reported in literature of which FSH-R1 and FSH-R3 have biological activity. Present study was undertaken to identify FSHR isoforms mediating FSH action on ovarian stem cells, using sheep OSE cells culture as the study model.

Methods

Cultures of sheep OSE cells (a mix of epithelial cells, VSELs, OGSCs and few contaminating red blood cells) were established with and without FSH 5IU/ml treatment. Effect of FSH treatment on self-renewal of VSELs and their differentiation into OGSCs was studied after 15 hrs by qRT-PCR using markers specific for VSELs (Oct-4A, Sox-2) and OGSCs (Oct-4). FSH receptors and its specific transcripts (R1 and R3) were studied after 3 and 15 hrs of FSH treatment by immunolocalization, in situ hybridization and qRT-PCR. FSHR and OCT-4 were also immuno-localized on sheep ovarian sections, in vitro matured follicles and early embryos.

Results

FSH treatment resulted in increased stem cells self-renewal and clonal expansion evident by the appearance of stem cell clusters. FSH receptors were expressed on ovarian stem cells whereas the epithelial cells were distinctly negative. An increase in R3 mRNA transcripts was noted after 3 hrs of FSH treatment and was reduced to basal levels by 15 hrs, whereas R1 transcript expression remained unaffected. Both FSHR and OCT-4 were immuno-localized in nuclei of stem cells, showed nuclear or ooplasmic localization in oocytes of primordial follicles and in cytoplasm of granulosa cells in growing follicles.

Conclusions

FSH modulates ovarian stem cells via FSH-R3 to undergo potential self-renewal, clonal expansion as ‘cysts’ and differentiation into oocytes. OCT-4 and FSHR proteins (required initially to maintain pluripotent state of VSELs and for FSH action respectively) gradually shift from nuclei to cytoplasm of developing oocytes and are later possibly removed by surrounding granulosa cells as the oocyte prepares itself for fertilization.

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Title: RETRACTED ARTICLE: Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3
Authors: Hiren Patel
Deepa Bhartiya
Seema Parte
Pranesh Gunjal
Snehal Yedurkar
Mithun Bhatt
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/1757-2215-6-52

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

RETRACTED ARTICLE: Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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