Endocrine Abstracts

The endocrine system is crucial in spermatogenesis and any hormonal alterations may affect fertility. Prolactin (Prl) plays a role in male reproduction, as evidenced by presence of prolactin receptors on various testicular cells. However, the exact mechanism and physiological role of testicular prolactin receptor during spermatogenesis remains elusive. Clinical conditions such as hyper- and hypo-prolactinemia are known to have deleterious effects on male reproduction. The aim of this study is to delineate the mechanisms by which hyper- and hypo-Prl affects male fertility. In vivo male rat model for hyper- and hypo-Prl was established using dopamine receptor antagonist (Fluphenazine) and agonist (Bromocriptine), respectively. Treatment with fluphenazine (hyper-Prl) and bromocriptine (hypo-Prl) for 60 days results in a significant decrease in fertility as compared to control male rats. This subfertility was due to an increase in pre- and post-implantation loss and a concomitant decrease in litter size when mated with control female rats. There was also a significant increase in the time taken for copulation after fluphenazine treatment. A significant reduction in sperm counts was observed in both the treatments. Sperm motility was found to be reduced significantly in hyper-Prl. Hormonal analysis revealed that LH, FSH, testosterone, and estrogen are significantly decreased in hyper-Prl group. In hypo-Prl group, LH and FSH were significantly increased, whereas testosterone and estrogen remained unaffected. Further, analysis of differential germ cell population by flow cytometry revealed that hyper-Prl group showed significant reduction in elongated and elongating spermatids and a concomitant increase in round spermatids indicating an arrest in differentiation of round to elongated spermatids. Additionally, these findings were confirmed by expression of cell-type specific markers by qPCR. To further delineate the molecular mechanisms underlying hyper-Prl v/s hypo-Prl, transcriptome analysis to study testicular gene expression was carried out. Differentially expressed genes obtained were subjected to gene ontology, pathway analysis, and enrichment map analysis. In conclusion, the results of this study demonstrate that altered levels of prolactin can have deleterious effects on different aspects of male fertility. It also suggests that the detrimental effects of hyper-Prl are more profound than hypo-Prl. Hyperprolactinemia could be one of the factors of idiopathic male infertility and routine screening of prolactin levels in infertile males should be recommended.