Mechanisms of Stress-Induced Spermatogenesis Impairment in Male Rats Following Unpredictable Chronic Mild Stress (uCMS).

Peng Zou,Guowei Zhang,Niya Zhou,Wang Yang,Jia Cao,Yingfei Zeng,Lei Sun,Xiaogang Wang,Qing Chen,Hongqiang Chen,Huan Yang,Jinyi Liu,Chang Liu,Lin Ao

doi:10.3390/ijms20184470

Peng Zou, Guowei Zhang + Show 12 more

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https://doi.org/10.3390/ijms20184470

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Abstract

The negative association between psychological stress and male fertility has been known for many years. This study was aimed at (i) identifying spermatogenesis impairment induced by psychological stress in rats and (ii) exploring the role of glucocorticoid receptor (GR) signaling in these adverse effects (if they exist). Male Sprague Dawley rats were exposed to a six-week period of unpredictable chronic mild stress (uCMS) along with cotreatment of GR antagonist RU486 (1 mg/kg/day). Testicular damage was assessed by testicular pathological evaluation, epididymal sperm concentration, serum testosterone levels, testicular apoptotic cell measurements, and cell cycle progression analyses. Rats in the uCMS group had decreased levels of serum testosterone and decreased epididymal sperm concentration. The uCMS-treated rats also had decreased numbers of spermatids and increased levels of apoptotic seminiferous tubules; additionally, cell cycle progression of spermatogonia was arrested at the G0/G1 phase. Furthermore, uCMS exposure caused an increase in serum corticosterone level and activated GR signaling in the testes including upregulated GR expression. RU486 treatment suppressed GR signaling and alleviated the damaging effects of stress, resulting in an increased epididymal sperm concentration. Overall, this work demonstrated for the first time that the activation of GR signaling mediates stress-induced spermatogenesis impairment and that this outcome is related to cell apoptosis and cell cycle arrest in germ cells.

Highlights

The negative association between psychological stress and male fertility has been known for many years
Rats in the unpredictable chronic mild stress (uCMS) + RU486 group showed increased stand-up times (p = 0.010), locomotor distance (p = 0.015), sucrose consumption (%) (p < 0.001), and decreased immobility time (p = 0.002) as compared to rats in the uCMS group. These results demonstrate that the uCMS model was successfully established and that RU486 was associated with antistress effects
Spermatogenesis impairment was induced by chronic stress in the uCMS rat model

Summary

Introduction

The negative association between psychological stress and male fertility has been known for many years. The first published study that examined the effect of psychological stress on testicular spermatogenesis was conducted in 1977 [1] These researchers found that Sertoli cells and spermatogonia were the only cell types found in the seminiferous tubules in some prisoners who were kept waiting for a long time before execution. In a study of 1215 young Danish men, researchers found that subjects with high levels of self-reported stress had worse semen parameters than subjects with low levels of self-reported stress [2]. This phenomenon has been demonstrated in animal experiments. Researchers found that dexamethasone-treated rats had 10 times more apoptotic germ cells than the control group [7]

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