Maternal androgen exposure induces intergenerational effects via paternal inheritance

in Journal of Endocrinology
Authors:
Yu Zhou Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Chao Lian Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Yingfei Lu Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Tianming Wang Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Chengcheng Zhao Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Cuilan Zhang Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Min Gong Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Jianquan Chen Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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Rong Ju Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

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https://orcid.org/0000-0003-3025-7213

Correspondence should be addressed to J Chen or R Ju: jqchen68@hotmail.com or jurong@njmu.edu.cn

*(Y Zhou and C Lian contributed equally to this work and share first authorship)

DOI:
https://doi.org/10.1530/JOE-23-0368
Volume/Issue:
Volume 262: Issue 2
Article Type:
Research Article
Article ID:
e230368
Online Publication Date:
24 Jun 2024
Copyright:
© the author(s) 2024
Restricted access
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Polycystic ovary syndrome (PCOS) is a condition resulting from the interaction between environmental factors and hereditary components, profoundly affecting offspring development. Although the etiology of this disease remains unclear, aberrant in utero androgen exposure is considered one of the pivotal pathogenic factors. Herein, we demonstrate the intergenerational inheritance of PCOS-like phenotypes in F2 female offspring through F1 males caused by maternal testosterone exposure in F0 mice. We found impaired serum hormone expression and reproductive system development in prenatal testosterone-treated F1 male and F2 female mice (PTF1 and PTF2). In addition, downregulated N6-methyladenosine (m6A) methyltransferase and binding proteins induced mRNA hypomethylation in the PTF1 testis, including frizzled-6 (Fzd6). In the PTF2 ovary, decreased FZD6 protein expression inhibited the mammalian target of rapamycin (mTOR) signaling pathway and activated Forkhead box O3 (FoxO3) phosphorylation, which led to impaired follicular development. These data indicate that epigenetic modification of the mTOR signaling pathway could be involved in the intergenerational inheritance of maternal testosterone exposure-induced impairments in the PTF2 ovary through male PTF1 mice.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2024
Article ID:
e230368
Article Type:
Research Article
Received Date:
23 Nov 2023
Accepted Date:
28 May 2024
Print Publication Date:
01 Aug 2024
Online Publication Date:
24 Jun 2024
Keywords:
polycystic ovary syndrome; paternal epigenetic inheritance; female offspring; frizzled-6; mTOR

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