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Estradiol modulated differentiation and dynamic growth of CD90+ spermatogonial stem cells toward Sertoli-like cells.

Authors
  • Sokouti Nasimi, Fatemeh1
  • Zahri, Saber1
  • Ahmadian, Shahin2
  • Bagherzadeh, Afsaneh2
  • Nazdikbin Yamchi, Nahideh2
  • Haghighi, Leila3
  • Bedate, Alberto Miranda4
  • Khalilzadeh, Balal2
  • Rahbarghazi, Reza5
  • Mahdipour, Mahdi6
  • 1 Department of Biology, Faculty of Basic Sciences, Mohaghegh Ardabili University, Ardabil, Iran. , (Iran)
  • 2 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. , (Iran)
  • 3 Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. , (Iran)
  • 4 Department of Immune Mechanisms (IMM), Center for Immunology of Infectious Diseases and Vaccines (IIV), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. , (Netherlands)
  • 5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. , (Iran)
  • 6 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: [email protected] , (Iran)
Type
Published Article
Journal
Life sciences
Publication Date
Dec 01, 2021
Volume
286
Pages
120041–120041
Identifiers
DOI: 10.1016/j.lfs.2021.120041
PMID: 34637796
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mouse CD90+ SSCs were enriched using the MACS technique and incubated with different doses of estradiol, ranging from 0.01 ng/mL to 500 μg/mL, for 7 days. The viability of SSCs was determined using an MTT assay. The combined effects of estradiol plus Sertoli cell differentiation medium on the orientation of SSCs toward Sertoli-like cells were also assessed. Using immunofluorescence imaging, we monitored protein levels of Oct3/4 after being exposed to estradiol. In addition, protein levels of testosterone, TF, and ABP were measured using ELISA. The expression of Sertoli cell-specific genes such as SOX9, GATA4, FSHR, TF, and ESR-1 and -2 was monitored using real-time PCR assay, and the effects of 14-day injection of estradiol on sperm parameters and Oct3/4 positive progenitor cells in a model of mouse were determined. Data showed that estradiol increased the viability of mouse SSCs in a dose-dependent manner compared to the control (p < 0.05). Along with these changes, cells displayed morphological changes and reduced Oct3/4 transcription factor levels compared to the control SSCs. 7-day incubation of SSCs with estradiol led to the up-regulation of SOX9, GATA4, FSHR, TF, and ESR-1 and -2, and levels of testosterone, TF, and ABP were increased compared to the control group (p < 0.05). The in-vivo examination noted that estradiol reduced sperm parameters coincided with morphological abnormalities (p < 0.05). Histological examination revealed pathological changes in seminiferous tubules and reduction of testicular Oct3/4+ progenitor cells. In conclusion, estradiol treatment probably can induce Sertoli cell differentiation of SSCs while exogenous administration leads to testicular progenitor cell depletion and infertility in long term. Copyright © 2021 Elsevier Inc. All rights reserved.

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