Chronic unpredictable stress (CUS) reduced phoenixin expression, induced abnormal sperm and testis morphology in male rats

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuropeptides Pub Date : 2024-06-07 DOI:10.1016/j.npep.2024.102447

Zahra Isnaini Mohamed, Mageswary Sivalingam, Ammu K. Radhakrishnan, Faizul Jaafar, Syafiq Asnawi Zainal Abidin

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Abstract

Chronic stress caused by prolonged emotional pressure can lead to various physiological issues, including reproductive dysfunction. Although reproductive problems can also induce chronic stress, the impact of chronic stress-induced reproductive dysfunction remains contentious. This study investigates the effects of chronic unpredictable stress (CUS) on reproductive neuropeptides, sperm quality, and testicular morphology. Sixteen twelve-week-old Sprague Dawley rats were divided into two groups: a non-stress control group and a CUS-induced group. The CUS regimen involved various stressors over 28 days, with both groups undergoing behavioural assessments through sucrose-preference and forced-swim tests. Hypothalamic gene expression levels of CRH, PNX, GPR173, kisspeptin, GnRH, GnIH, and spexin neuropeptides were measured via qPCR, while plasma cortisol, luteinizing hormone (LH), and testosterone concentrations were quantified using ELISA. Seminal fluid and testis samples were collected for sperm analysis and histopathological evaluation, respectively. Results showed altered behaviours in CUS-induced rats, reflecting stress impacts. Hypothalamic corticotropin-releasing hormone (CRH) expression and plasma cortisol levels were significantly higher in CUS-induced rats compared to controls (p < 0.05). Conversely, phoenixin (PNX) expression decreased in the CUS group (p < 0.05), while kisspeptin, spexin, and gonadotropin-inhibitory hormone (GnIH) levels showed no significant differences between groups. Despite a significant increase in GnRH expression (p < 0.05), plasma LH and testosterone concentrations were significantly lower (p < 0.05) in CUS-induced rats. Histopathological analysis revealed abnormal testis morphology in CUS-induced rats, including disrupted architecture, visible interstitial spaces between seminiferous tubules, and absence of spermatogenesis. In conclusion, CUS affects reproductive function by modulating PNX and GnRH expression, influencing cortisol levels, and subsequently reducing plasma LH and testosterone concentrations. This study highlights the complex interplay between chronic stress and reproductive health, emphasizing the significant impact of stress on reproductive functions.

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慢性不可预知应激（CUS）会降低雄性大鼠凤凰素的表达，诱发精子和睾丸形态异常

长期的情绪压力会导致各种生理问题，包括生殖功能障碍。虽然生殖问题也会诱发慢性应激，但慢性应激诱发生殖功能障碍的影响仍存在争议。本研究调查了慢性不可预测应激（CUS）对生殖神经肽、精子质量和睾丸形态的影响。16 只 12 周大的 Sprague Dawley 大鼠被分为两组：非应激对照组和 CUS 诱导组。CUS方案包括28天的各种应激，两组均通过蔗糖偏好和强迫游泳测试进行行为评估。通过 qPCR 测量了 CRH、PNX、GPR173、kisspeptin、GnRH、GnIH 和 spexin 神经肽的下丘脑基因表达水平，同时使用 ELISA 对血浆皮质醇、促黄体生成素（LH）和睾酮浓度进行了量化。收集的精液和睾丸样本分别用于精子分析和组织病理学评估。结果显示，CUS 诱导的大鼠行为发生了改变，这反映了应激的影响。与对照组相比，CUS 诱导的大鼠下丘脑促肾上腺皮质激素释放激素（CRH）的表达和血浆皮质醇水平显著升高（p < 0.05）。相反，凤凰素（PNX）的表达在 CUS 组中下降（p < 0.05），而吻肽、spexin 和促性腺激素抑制激素（GnIH）的水平在组间无明显差异。尽管 GnRH 表达明显增加（p < 0.05），但 CUS 诱导的大鼠血浆 LH 和睾酮浓度明显降低（p < 0.05）。组织病理学分析表明，CUS诱导的大鼠睾丸形态异常，包括结构紊乱、曲细精管之间有明显的间隙以及没有精子发生。总之，CUS 通过调节 PNX 和 GnRH 的表达、影响皮质醇水平以及降低血浆 LH 和睾酮浓度来影响生殖功能。这项研究突出了慢性压力与生殖健康之间复杂的相互作用，强调了压力对生殖功能的重大影响。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.