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 ± 4.2g were divided into four groups including normal Zn diet group 30mg/(kg•d), BPA exposure group 150mg/(kg•d), zinc deficiency diet group 7.5mg/(kg•d), and BPA + ZD combined exposure group (BPA 150mg/(kg•d) + ZD 7.5mg/(kg•d)). The mice were kept for 8weeks. 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.