Epigenetics, cryptorchidism, and infertility.

IF 2.4 3区医学 Q2 ANDROLOGY

Basic and Clinical Andrology Pub Date : 2023-09-21 DOI:10.1186/s12610-023-00199-7

Faruk Hadziselimovic, Gilvydas Verkauskas, Michael B Stadler

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引用次数: 0

Abstract

Background: Cryptorchid boys with defective mini-puberty and impaired differentiation of Ad spermatogonia (high infertility risk) have altered expression of several genes encoding histone methyltransferases compared to patients with intact differentiation of gonocytes into Ad spermatogonia (low infertility risk).

Results: High infertility risk cryptorchid boys display hypogonadotropic hypogonadism, which, together with the diminished expression of histone deacetylases and increased expression of HDAC8 decrotonylase, indicates altered histone marks and, thus, a perturbed histone code. Curative GnRHa treatment induces normalization of histone methyltransferase, chromatin remodeling, and histone deacetylase gene expression. As a result, histone changes induce differentiation of Ad spermatogonia from their precursors and, thus, fertility. In this short report, we describe key functions of histone lysine methyltransferases, chromatin remodeling proteins, and long-noncoding RNAs, and discuss their potential roles in processes leading to infertility.

Conclusion: Our findings suggest that epigenetic mechanisms are critical to better understanding the root causes underlying male infertility related to cryptorchidism and its possible transgenerational transmission.

Abstract Image

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表观遗传学、隐睾和不孕。

背景：与生殖细胞完整分化为Ad精原细胞的患者（低不孕风险）相比，具有青春期缺陷和Ad精源细胞分化受损（高不孕风险）的隐睾男孩已经改变了编码组蛋白甲基转移酶的几个基因的表达，其与组蛋白脱乙酰酶的表达减少和HDAC8脱乙酰基酶的表达增加一起，表明组蛋白标记改变，从而导致组蛋白密码紊乱。GnRHa治疗可诱导组蛋白甲基转移酶、染色质重塑和组蛋白脱乙酰酶基因表达正常化。因此，组蛋白的变化诱导Ad精原细胞从其前体分化，从而诱导生育能力。在这份简短的报告中，我们描述了组蛋白赖氨酸甲基转移酶、染色质重塑蛋白和长非编码RNA的关键功能，并讨论了它们在导致不孕过程中的潜在作用。结论：我们的研究结果表明，表观遗传学机制对于更好地理解与隐睾相关的男性不育的根本原因及其可能的转基因传播至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Basic and Clinical Andrology Medicine-Urology

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

22 weeks

期刊介绍： Basic and Clinical Andrology is an open access journal in the domain of andrology covering all aspects of male reproductive and sexual health in both human and animal models. The journal aims to bring to light the various clinical advancements and research developments in andrology from the international community.