In vivo exposure to bisphenol F induces oxidative testicular toxicity: role of Erβ and p53/Bcl-2 signaling pathway

Abstract

IntroductionBisphenol F (BPF), an alternative to bisphenol A has been implicated as a gonadotoxic substance. BPF has been shown to induce hormonal imbalance and testicular oxidative damage. However, the mechanism associated with BPF-induced testicular toxicity has not been fully explored. This study was designed to explore the role of tumor protein (p53)/ B-cell lymphoma 2 (BCl-2) signaling and oestrogen receptor beta (Erβ) in BPF-induced testicular toxicity.MethodsMale Wistar rats were randomized into control (Cntrl), BPF-treated (10, 30, and 50 mg/kg for low dose (BPF-L), medium dose (BPF-M), and high dose (BPF-H) respectively), and BPF-treated recovery (Cntrl-R, BPF-L-R, BPF-M-R, and BPF-H-R). The administration was via gavage and lasted for 28 days and the animals in the recovery groups were allowed 28-days exposure free period for recovery from BPF exposure.ResultsBPF resulted in the distortion of the testicular histoarchitecture, which was accompanied by a significant rise in testicular gamma-lutamyl transferase and lactate dehydrogenase activities but a decline in sorbitol dehydrogenase activities. Also, BPF caused a significant reduction in plasma gonadotropin-releasing hormone, luteinising hormone, follicle-stimulating hormone, and testosterone, which was associated with the downregulation of testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities. Furthermore, BPF induced testicular inflammation, redox imbalance, and apoptosis, accompanied by distortion in p53/BCl-2 signaling and overexpression of Erβ. Again, the observed toxic effects of BPF were dose-dependent and not completely reversed by BPF cessation.DiscussionBisphenol F induced gonadotoxicity by distorting p53/BCl2 signaling and the expression of Erβ. These observed alterations were not completely reversed after the cessation of BPF exposure.

Zinc ameliorates acrylamide-induced oxidative stress and apoptosis in testicular cells via Nrf2/HO-1/NfkB and Bax/Bcl2 signaling pathway

“…The findings that acrylamide impaired the HPT axis are similar to that of Gül et al [ 30 ] and Erdemli et al [ 31 ]. These observed impairment in testicular functions can be ascribed to oxidative stress [ 32 , 33 ], inflammatory response [ 23 , 34 ], and apoptosis [ 35 , 36 ].…”

Naringin from sweet orange peel improves testicular function in high fat diet-induced diabetic rats by modulating xanthine oxidase/uric acid signaling and maintaining redox balance

“…XO, on the other hand, utilizes oxygen to generate hydrogen peroxide (H2O2) and superoxide ions [ 41 ]; aside from the production of H 2 O 2 and superoxide from the activities of XO, the UA, which is the final product is also a pro-oxidant. Although UA acts as an antioxidant, it contributes to oxidative stress when produced in excess [ 6 ]. The observed increase in testicular XO and UA following T2DM suggests that XO/UA could be the primary mechanism responsible for the T2DM-induced oxide-inflammatory response observed in this study.…”

“…Testicular XO activities were determined as previously described [ 6 ], while UA concentration was determined using colorimetric methods (Precision, UK) using a spectrophotometer.…”

“…However, the mechanisms associated with oxidative testicular damage have not been fully explored. Although xanthine oxidase (XO)/uric acid (UA) signaling has been shown to disrupt testicular functions [ 6 – 8 ], its role in T2DM-induced testicular toxicity has not been fully established.…”

Impact of stress on male fertility: role of gonadotropin inhibitory hormone

“…Neurons responsible for the synthesis of GnIH are present in the mid-ventral continuum from the diagonal band of Broca to the mediobasal hypothalamus ( 23 ), while those regulating the secretion of gonadotrophic hormones extend to the median eminence to modulate the synthesis of FSH and LH ( 13 , 24 ). The released LH and FSH then regulate the synthesis of gonadal hormones which in turn send negative feedback to the hypothalamus and anterior pituitary gland to keep the reproductive axis within the operating limits required for optimal reproductive functions ( 25 ). This closed loop is called the hypothalamic-pituitary-gonadal (HPG) axis, and it is known to be solely regulated in the hypothalamus via GnRH ( 26 ) until the discovery of GnIH.…”