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17α-乙炔基雌二醇改变了小鼠睾丸的表观遗传特征和组蛋白-鱼精蛋白的转换。

17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice.

机构信息

Laboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic.

Department of Urology, Pediatric Urology and Andrology, Molecular Andrology, Biomedical Research Center of the Justus-Liebig University, Giessen, Germany.

出版信息

Reprod Biol Endocrinol. 2024 Nov 4;22(1):135. doi: 10.1186/s12958-024-01307-6.

DOI:10.1186/s12958-024-01307-6
PMID:39491035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11533287/
Abstract

Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.

摘要

精子发生始于睾丸生精上皮中的青春期开始。这是一个复杂的过程，受到内分泌系统的精细控制。一般来说，类固醇激素和雌激素的生理调节作用，由于其化学性质，容易受到作为内分泌干扰物（EDs）的外源因素的破坏。17α-乙炔雌二醇（EE2）是一种环境污染物，具有已确认的 ED 活性，并且对单倍体生殖细胞的精子发生和染色质重塑有明显影响。我们的研究目的是评估两种剂量（2.5ng/ml；2.5μg/ml）的 EE2 对精子发生过程中组蛋白-鱼精蛋白交换和表观遗传特征的可能影响，在小鼠中进行了多/世代研究。我们的结果表明，在暴露动物的精子核中，组蛋白-鱼精蛋白交换受到损害，组蛋白保留显著增加，同时伴随着组蛋白翻译后修饰（PTMs）丰度的变化，H3K9Ac 显著增加，而鱼精蛋白 1 启动子甲基化状态发生部分变化。此外，当没有观察到直接的跨代效应时，个体的分子表型变化部分传递到后代。最后，在 EE2 暴露后，精子核中组蛋白保留的特定定位及其特定的 PTMs 谱可能表明雌激素通过表观遗传机制对精子运动和早期胚胎发育的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/2ff73da4df46/12958_2024_1307_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/a984729633b2/12958_2024_1307_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/c0b7846244c8/12958_2024_1307_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/f150005c3246/12958_2024_1307_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/28a5a533e5c9/12958_2024_1307_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/7dc53d412cd9/12958_2024_1307_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/9e8753d60d3c/12958_2024_1307_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/2ff73da4df46/12958_2024_1307_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/a984729633b2/12958_2024_1307_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/c0b7846244c8/12958_2024_1307_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/f150005c3246/12958_2024_1307_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/28a5a533e5c9/12958_2024_1307_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/7dc53d412cd9/12958_2024_1307_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/9e8753d60d3c/12958_2024_1307_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b05/11533287/2ff73da4df46/12958_2024_1307_Fig7_HTML.jpg

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