Endocrine Abstracts

Introduction: Chronic stress caused by prolonged emotional pressure may cause to multiple physiological problems including reproductive dysfunction. There is no doubt that infertility can cause chronic stress. However, the effect of chronic stress-induced reproductive dysfunction is still debatable. Thus, this study aims to demonstrate CUS effect on reproductive system.

Methodology: Sprague Dawley (SD) rats (n=16) were divided into two groups: i) non-stress control group ii) CUS-induced group. The CUS consists of different stressors that were induced for 28 days, and each group was subjected to behavioural tests. To identify the effect of CUS at the hypothalamic level, gene expression study was done to determine the expression of stress and reproductive neuropeptides. As hypothalamic neuropeptides responsible to regulate hormone circulation, ELISA test was done to measure the plasma stress and reproductive hormones concentration. To identify the effect of CUS on the peripheral level, histopathologic evaluation of the rats’ testis was done with H& E staining. The seminal fluid was analysed for sperm count and morphological changes.

Results: The stress model was confirmed by the sucrose-preference and force-swimming test. Hypothalamically, the expression of corticotropin-releasing hormones (CRH) in CUS-induced rats increased significantly compared to control group (P<0.05). The upregulated CRH was supported by the elevation of plasma cortisol in CUS-induced rats (P<0.05). The effect of CUS also downregulated phoenixin (PNX) expression in the hypothalamus of CUS-induced rats by 0.5 fold lower than the control group (P<0.05). However, kisspeptin, spexin (SPX) and gonadotropin-inhibitory hormone (GnIH) showed no difference between the two groups. The primary regulator of reproductive system, gonadotropin-stimulating hormone (GnRH) expressed significantly higher than control (P<0.05). Despite the increased expression of GnRH, plasma LH and testosterone concentration were significantly low (P<0.05) in CUS-induced rats compared to control group. The effect of CUS demonstrated anomalous testis morphology of CUS-induced rats consisting of abnormal architecture with visible interstitial spaces between seminiferous tubules and the absence of spermatogenesis. The reproductive deficit of CUS-induced rats was further demonstrated with an increase of 20% in abnormal sperm count compared to only 3% in control group (P<0.0001).

Conclusions: Our CUS model of chronic stress demonstrated a correlation with reproductive function where chronic stress caused low concentration of reproductive hormones, high abnormal sperm count and abnormal testis morphology. These findings interestingly suggest the correlation with low phoenixin expression as reproductive system regulator.