Comparative study of environmental pollutants bisphenol A and bisphenol S on sexual differentiation of anteroventral periventricular nucleus and spermatogenesis

Abstract

Background: Bisphenol A is well known endocrine-disrupting chemical while Bisphenol S was considered a safe alternative. The present study aims to examine the comparative effects of xenobiotic bisphenol-A (BPA) and its substitute bisphenol-S (BPS) on spermatogenesis and development of sexually dimorphic nucleus population of dopaminergic neurons in the anteroventral periventricular nucleus (AVPV) of the hypothalamus in male pups.

Methods: Sprague Dawley rat's pups were administered subcutaneously at the neonatal stage from postnatal day PND1 to PND 27. Thirty animals were divided into six experimental groups (6 animals/group). The first group served as control and was provided with normal olive oil. The four groups were treated with 2 μg/kg and 200 μg/kg of BPA and BPS, respectively. The sixth group was given with 50 μg/kg of estradiol dissolved in olive oil as a standard to find the development of dopaminergic tyrosine hydroxylase neurons in AVPV regions. Histological analysis for testicular tissues and immunohistochemistry for brain tissues was performed.

Results: The results revealed adverse histopathological changes in testis after administration of different doses of BPA and BPS. These degenerative changes were marked by highly significant (p < 0.001) decrease in tubular and luminal diameters of seminiferous tubule and epithelial height among bisphenols treated groups as compared to control. Furthermore, significantly increased (p < 0.001) TH-ir cell bodies in the AVPV region of the brain with 200 μg/kg dose of BPA and BPS was evident.

Conclusion: It is concluded that exposure of BPA and BPS during a critical developmental period can structural impairments in testes and affects sexual differentiation of a dimorphic dopaminergic population of AVPV region of hypothalamus in the male brain.

Keywords: AVPV; Bisphenol A; Bisphenol S; Endocrine disruptor; Immunohistochemistry.

Fig. 1

Photomicroghaph of 27 days old neonatal male rat seminiferous tubules(H&E, 40X) from: (a) Control; showing normal morphology of closely packed tubules with basal lamina, stratification and increased spermatogenic epithelium Spermatogonia, primary spermatocytes and early spermatids well developed lumen, (b) BPA group treated with 2 μg/kg of dose; showing noticeable increase in interstitial spaces between destructed tubules and basal lamina, decrease in epithelial height, only spermatogonia and large lumen, (c) BPA group treated with 200 μg/kg; showing decreased tubular diameter damaged interstitial tissues and increased interstitial spaces, narrow lumen, (d) BPS 2 μg/kg treated group showing semineferious tubules without interstitial space, minimal damage to epithelial, decrease in lumen diameter, (e) BPS 200 μg/kg; showing no interstitial space, normal spermatogenesis and basal lamina around tubules and very short lumen with early spermatids. Interstitial space (IS), Spermatogonia(S), Primary spermatocytes (PS), Early spermatids (ES), Epithelial Height (EH), Interstitial tissues (IT), Basal lamina (BL), Lumen (L)

Fig. 2

Photomicrograph (10X) of TH-immunoreactive cells in AVPV of representative Sprague Dawley male rat pups that were neonatal treated with BPA 2 μg/kg (a), BPA 200 μg/kg (b), BPS 2 μg/kg (c), BPS 200 μg/kg (d), Control (e), Estradiol (f). Omitted controls g and h show no significance results