Depression, anxiety, and stress impair sperm quality via dysregulation of the mitochondrial PDK-PDC axis.

IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Wang Wang, Wang Qikai, Wang Zilin, Shao Junyan, Jiang Xiaocui, Liu Qi, Chen Shuhui, Zhu Yangyang, Gao Mengjie, Chen Siyi, Cao Jigang, Xiao Min
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Abstract

Male infertility, a significant global public health challenge, arises from multifactorial interactions involving genetic, metabolic, and psychological factors. While psychological stress (depression/anxiety/stress, DAS) is increasingly linked to impaired sperm quality, its molecular mechanisms remain unclear. This cross-sectional study investigates mitochondrial metabolic reprogramming via the pyruvate dehydrogenase kinase (PDK)-pyruvate dehydrogenase complex (PDC) axis under psychological stress, exploring multidimensional impacts on semen quality.Approved by three tertiary hospitals in Central China, 557 participants were categorized into DAS and non-DAS groups based on DASS-21 scores, with clinical histories and semen samples collected. Targeted metabolomics (ATP/pyruvate/lactate), lipidomics (free fatty acids), and RT-qPCR (PDK1-4, PDH mRNA) were performed. Results revealed significantly reduced sperm motility in the DAS group (p < 0.01). Mechanistically, DAS upregulated PDK2/PDK4 expression and suppressed PDH expression, driving metabolic reprogramming and mitochondrial dysfunction. This study provides the first evidence that psychological stress impairs sperm motility via PDK-PDC axis dysregulation, offering novel mechanistic insights and potential therapeutic targets for male infertility.

抑郁、焦虑和压力通过线粒体PDK-PDC轴的失调损害精子质量。
男性不育是一项重大的全球公共卫生挑战,是由涉及遗传、代谢和心理因素的多因素相互作用引起的。虽然心理压力(抑郁/焦虑/压力,DAS)越来越多地与精子质量受损联系在一起,但其分子机制尚不清楚。本横断面研究通过心理压力下丙酮酸脱氢酶激酶(PDK)-丙酮酸脱氢酶复合物(PDC)轴研究线粒体代谢重编程,探讨对精液质量的多维影响。经华中三所三级医院批准,557名参与者根据DASS-21评分分为DAS组和非DAS组,并收集了临床病史和精液样本。进行了靶向代谢组学(ATP/丙酮酸/乳酸)、脂质组学(游离脂肪酸)和RT-qPCR (PDK1-4, PDH mRNA)。结果显示,DAS组精子活力显著降低(p
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来源期刊
Reproductive Biology and Endocrinology
Reproductive Biology and Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.30%
发文量
161
审稿时长
4-8 weeks
期刊介绍: Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences. The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
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