The Silent Struggle: Chronic Unpredictable Stress (CUS) Impair the Expression of Reproductive Neuropeptide Genes and Hormones and Seminal Fluid Quality

The chronic unpredictable stress (CUS) paradigm, commonly employed in animal models, mimics the random and prolonged exposure to diverse unpredictable stressors experienced by humans. Recent studies have revealed that CUS impairs spermatogenesis. However, the underlying mechanisms involving reproductive neuropeptides and hormones remain elusive. This study aims to elucidate the effect of CUS on the reproductive neuropeptide genes and hormones as well as seminal fluid quality. Sprague Dawley (SD) rats, aged 3 months, were divided into control and CUS groups. The CUS group was randomly subjected to various stressors for 28 days. Real-time PCR was utilised to evaluate the mRNA expression of reproductive neuropeptides, including phoenixin, kisspeptin, spexin, gonadotropin-inhibitory hormone (GnIH), and gonadotropin-releasing hormone (GnRH). The results demonstrated significantly lower phoenixin expression (p<0.05) in CUS rats compared to controls, whereas GnRH exhibited significantly higher expression (p<0.05) in CUS rats. The concentrations of circulating reproductive hormones, luteinising hormone (LH) and testosterone were quantified. CUS rats displayed significantly lower plasma LH concentrations compared to controls, and the downstream reproductive hormone, plasma testosterone concentration, was significantly reduced (p<0.05) in CUS rats. Furthermore, CUS rats exhibited a decline in seminal fluid quality, particularly an increase in abnormal sperm. Therefore, our findings indicate that CUS negatively impacts reproductive function through alterations in the expression of reproductive neuropeptides such as phoenixin and GnRH and hormonal dysregulation involving LH and testosterone.