Estrogen suppresses SOX9 and activates markers of female development in a human testis-derived cell line

BMC Molecular and Cell Biology

Andrew J. Pask¹  Deidre M. Mattiske¹  Melanie K. Stewart¹ 

[1] School of BioSciences, The University of Melbourne, 3010, Parkville, VIC, Australia;

关键词: Estrogen;    Sertoli cells;    Testis;    Sex determination;   

DOI  :  10.1186/s12860-020-00307-9

来源: Springer

【 摘 要 】

BackgroundThe increasing incidence of reproductive disorders in humans has been attributed to in utero exposure to estrogenic endocrine disruptors. In particular, exposure of the developing testis to exogenous estrogen can negatively impact male reproductive health. To determine how estrogens impact human gonad function, we treated the human testis-derived cell line NT2/D1 with estrogen and examined its impact on SOX9 and the expression of key markers of granulosa (ovarian) and Sertoli (testicular) cell development.ResultsEstrogen successfully activated its cognate receptor (estrogen receptor alpha; ESR1) in NT2/D1 cells. We observed a significant increase in cytoplasmic SOX9 following estrogen treatment. After 48 h of estrogen exposure, mRNA levels of the key Sertoli cell genes SOX9, SRY, AMH, FGF9 and PTGDS were significantly reduced. This was followed by a significant increase in mRNA levels for the key granulosa cell genes FOXL2 and WNT4 after 96 h of estrogen exposure.ConclusionsThese results are consistent with estrogen's effects on marsupial gonads and show that estrogen has a highly conserved impact on gonadal cell fate decisions that has existed in mammals for over 160 million years. This effect of estrogen presents as a potential mechanism contributing to the significant decrease in male fertility and reproductive health reported over recent decades. Given our widespread exposure to estrogenic endocrine disruptors, their effects on SOX9 and Sertoli cell determination could have considerable impact on the adult testis.

【 授权许可】

CC BY