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GGA1 参与应激状态下的小鼠精子发生。

GGA1 participates in spermatogenesis in mice under stress.

机构信息

The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, P.R. China.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, P.R. China.

出版信息

PeerJ. 2023 Aug 3;11:e15673. doi: 10.7717/peerj.15673. eCollection 2023.

Abstract

BACKGROUND

Infertility is recognized as a common and worrisome problem of human reproduction worldwide. Based on previous studies, male factors account for about half of all infertility cases. Exposure to environmental toxicants is an important contributor to male infertility. Bisphenol A (BPA) is the most prominent toxic environmental contaminant worldwide affecting the male reproductive system. BPA can impair the function of the Golgi apparatus which is important in spermatogenesis. GGA1 is known as Golgi-localized, gamma adaptin ear-containing, ARF-binding protein 1. Previously, it has been shown that GGA1 is associated with spermatogenesis in , however, its function in mammalian spermatogenesis remains unclear.

METHODS

knockout mice were generated using the CRISPR/Cas9 system. male mice and wild-type littermates received intraperitoneal (i.p.) injections of BPA (40 µg/kg) once daily for 2 weeks. Histological and immunofluorescence staining were performed to analyze the phenotypes of these mice.

RESULTS

Male mice lacking had normal fertility without any obvious defects in spermatogenesis, sperm count and sperm morphology. ablation led to infertility in male mice exposed to BPA, along with a significant reduction in sperm count, sperm motility and the percentage of normal sperm. Histological analysis of the seminiferous epithelium showed that spermatogenesis was severely disorganized, while apoptotic germ cells were significantly increased in the null mice exposed to BPA. Our findings suggest that protects spermatogenesis against damage induced by environmental pollutants.

摘要

背景

不孕不育被认为是全世界人类生殖中常见且令人担忧的问题。根据之前的研究,男性因素约占所有不孕病例的一半。暴露于环境毒物是导致男性不育的一个重要因素。双酚 A(BPA)是全世界最突出的有毒环境污染物,会影响男性生殖系统。BPA 可以损害高尔基体的功能,而高尔基体在精子发生中很重要。GGA1 被称为高尔基定位、γ衔接蛋白含有、ARF 结合蛋白 1。以前已经表明,GGA1 与 中的精子发生有关,但是其在哺乳动物精子发生中的功能尚不清楚。

方法

使用 CRISPR/Cas9 系统生成 敲除小鼠。雄性小鼠和野生型同窝仔鼠每天腹膜内(i.p.)注射 BPA(40µg/kg)一次,连续 2 周。进行组织学和免疫荧光染色来分析这些小鼠的表型。

结果

缺乏 的雄性小鼠具有正常的生育能力,精子发生、精子计数和精子形态均无明显缺陷。BPA 暴露导致 缺失的雄性小鼠不育,精子计数、精子活力和正常精子比例显著降低。对曲细精管上皮的组织学分析表明,BPA 暴露的 缺失小鼠的精子发生严重紊乱,而凋亡的生殖细胞明显增加。我们的研究结果表明, 可保护精子发生免受环境污染物的损伤。

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