BPA Exacerbates Zinc Deficiency–Induced Testicular Tissue Inflammation in Male Mice Through the TNF-α/NF-κB/Caspase8 Signaling Pathway

Abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical that is toxic to reproduction. Zinc (Zn) plays an important role in male reproductive health. Zn deficiency (ZD) can co-exist with BPA. In order to investigate the specific mechanism of reproductive damage caused by BPA exposure in ZD male mice, a mouse model of ZD, BPA exposure, and their combined exposure was established in this study. Forty 4-week-old SPF male ICR mice with an average body weight of 31.7 ± 4.2 g were divided into four groups including normal Zn diet group 30 mg/(kg•d), BPA exposure group 150 mg/(kg•d), zinc deficiency diet group 7.5 mg/(kg•d), and BPA + ZD combined exposure group (BPA 150 mg/(kg•d) + ZD 7.5 mg/(kg•d)). The mice were kept for 8 weeks. The results showed that the testicular tissue structure was disturbed, and semen quality, serum Zn, testicular tissue Zn, and testicular tissue free Zn ions were decreased in the BPA-exposed and ZD groups. The expression of zinc transporters (ZIP7, ZIP8, ZIP13, and ZIP14) in testicular tissue was changed. The expressions of pro-inflammatory cytokines including TNF-α and IL-1β as well as inflammatory pathway-related proteins (IKB-α, p-IKB-α, NF-κB, p-NF-κB, Caspase8, and Caspase3) were increased, while the expressions of anti-inflammatory cytokines (TGF-β and IL-10) were decreased. The changes in the above indexes in the BPA + ZD group were more obvious. Both BPA exposure and ZD can induce testicular tissue inflammation through the TNF-α/NF-κB/Caspase8 signaling pathway, and BPA further aggravates zinc deficiency-induced testicular tissue inflammation and apoptosis damage.