Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic–pituitary–testicular axis

Abstract

Reproductive physiology involves complex biological processes that can be disrupted by exposure to environmental contaminants. The effects of bisphenol A (BPA) on spermatogenesis and sperm quality is still unclear. The objective of this study was to investigate the reproductive toxicity of BPA at dosages considered to be safe (5 or 25mg BPA/kg/day). We assessed multiple sperm parameters, the relative expression of genes involved in the central regulation of the hypothalamic-pituitary-testicular axis, and the serum concentrations of testosterone, estradiol, LH and FSH. BPA exposure reduced sperm production, reserves and transit time. Significant damage to the acrosomes and the plasma membrane with reduced mitochondrial activity and increased levels of defective spermatozoa may have compromised sperm function and caused faster movement through the epididymis. BPA exposure reduced the serum concentrations of testosterone, LH and FSH and increased the concentration of estradiol. The relative gene expression revealed an increase in gonadotropin releasing hormone receptor (Gnrhr), luteinizing hormone beta (Lhb), follicle stimulating hormone beta (Fshb), estrogen receptor beta (Esr2) and androgen receptor (Ar) transcripts in the pituitary and a reduction in estrogen receptor alpha (Esr1) transcripts in the hypothalamus. In this study, we demonstrated for the first time that adult male exposure to BPA caused a reduction in sperm production and specific functional parameters. The corresponding pattern of gene expression is indicative of an attempt by the pituitary to reestablish normal levels of LH, FSH and testosterone serum concentrations. In conclusion, these data suggest that at dosages previously considered nontoxic to reproductive function, BPA compromises the spermatozoa and disrupts the hypothalamic-pituitary-gonadal axis, causing a state of hypogonadotropic hypogonadism.

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

“…BPA-induced neurotoxicity corroborates with mitochondrial dysfunctions and apoptosis (7). Exposure to BPA in adult rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis (8). BPA exposure causes abnormalities of liver function and hepatic damage associated with mitochondrial apoptosis (9).…”

Protective effect of Cordyceps militaris extract against bisphenol A induced reproductive damage

“…Finally, it is catalyzed to testosterone by 17β-HSD. Recent studies showed that BPA reduced testosterone and LH serum concentration by disrupting the negative feedback mechanisms of hypothalamic-pituitary-gonadal axis [Wisniewski et al 2015]. BPA is considered a potential endocrine disruptor that can inhibit testosterone production by inhibiting CYP11A1, 3β-HSD, CYP17A1, and 17β-HSD [Peretz and Flaws 2013;Ye et al 2011].…”

Cytotoxic effects of ZnO nanoparticles on mouse testicular cells

“…61,62 In particular, two previous studies 26,27 using exposure protocols based on daily administration of the NPs for 35 days have established that ZnO NPs have cytotoxic actions on testicular germ cells in a dose-dependent manner. In line with these studies, we found that a single systemic injection of ZnO NPs caused alteration in the structure of seminiferous epithelium and the production of morphologically abnormal spermatozoa.…”