Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model

Hang-Soo Park; Rishi Man Chugh; Abdeljabar El Andaloussi; Elie Hobeika; Sahar Esfandyari; Amro Elsharoud; Mara Ulin; Natalia Garcia; Mahmood Bilal; Ayman Al-Hendy

doi:10.1038/s41598-021-84216-7

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Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model

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Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model

Hang-Soo Park, Rishi Man Chugh, Abdeljabar El Andaloussi, Elie Hobeika, Sahar Esfandyari, Amro Elsharoud, Mara Ulin, Natalia Garcia, Mahmood Bilal and Ayman Al-Hendy

Scientific reports, Vol.11(1), pp.4525-4525

02/25/2021

DOI: 10.1038/s41598-021-84216-7

PMID: 33633319

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Abstract

Primary ovarian insufficiency (POI) is defined as the loss of ovarian function before 40 years of age. It clinically manifests as amenorrhea, infertility, and signs of estrogen insufficiency. POI is frequently induced by chemotherapy. Gonadotoxic chemotherapy reagents damage granulosa cells, which are essential for follicular function and development. Our recently published studies demonstrated that intraovarian transplantation of human mesenchymal stem cells (hMSCs) can restore fertility in a chemotherapy-induced POI mouse model. However, the regenerative mechanism underlying the hMSC effect in POI mice is not fully understood. Here, we report that the hMSC secretome increased the proliferation of human granulosa cells (HGrC1). We showed by FACS analysis that treatment of HGrC1 cells with hMSC-conditioned media (hMSC CM) stimulates cellular proliferation. We also demonstrated that the expression of steroidogenic enzymes involved in the production of estrogen, CYP19A1 and StAR, are significantly elevated in hMSC CM-treated HGrC1 cells. Our data suggest that hMSC CM stimulates granulosa cell proliferation and function, which may explain the therapeutic effect of hMSCs in our chemotherapy-induced POI animal model. Our findings indicate that the hMSC secretome may be a novel treatment approach for restoring granulosa cell and ovarian function in patients with POI.

Details

Title: Subtitle: Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model
Creators: Hang-Soo Park - University of Chicago
Rishi Man Chugh - University of Illinois Chicago
Abdeljabar El Andaloussi - University of Illinois Chicago
Elie Hobeika - Fertility Centers of Illinois
Sahar Esfandyari - University of Illinois Chicago
Amro Elsharoud - University of Illinois Chicago
Mara Ulin - University of Illinois Chicago
Natalia Garcia - University of Illinois Chicago
Mahmood Bilal - Rosalind Franklin University of Medicine and Science
Ayman Al-Hendy - University of Chicago
Resource Type: Journal article
Publication Details: Scientific reports, Vol.11(1), pp.4525-4525
DOI: 10.1038/s41598-021-84216-7
PMID: 33633319
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: name: University of Illinois at Chicago, a start-up fund.; name: University of Chicago, a start-up fund
Language: English
Date published: 02/25/2021
Academic Unit: Pathology
Record Identifier: 9984185165702771

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