Protective mechanisms of zinc and/or selenium supplementation against BPA-induced male and offspring reproductive toxicity: Insights from multiomics analysis

Jing Ma; Yuanjing Li; Yuejia Li; Jiajie Bi; Junsheng Liu; Junling Li; Fanshun Meng; Lei Yan; Jianan Wen; Xueting Wang; Jian Qin; Shusong Wang; Rong Du

doi:10.1016/j.envint.2025.109975

Protective mechanisms of zinc and/or selenium supplementation against BPA-induced male and offspring reproductive toxicity: Insights from multiomics analysis

Environ Int. 2025 Dec 4:207:109975. doi: 10.1016/j.envint.2025.109975. Online ahead of print.

Authors

Jing Ma¹, Yuanjing Li², Yuejia Li³, Jiajie Bi⁴, Junsheng Liu³, Junling Li⁵, Fanshun Meng⁵, Lei Yan⁵, Jianan Wen⁵, Xueting Wang⁵, Jian Qin⁶, Shusong Wang⁷, Rong Du⁸

Affiliations

¹ College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801 Shanxi, China; Hebei Key Laboratory of Reproductive Medicine, Hebei Reproductive Health Hospital, Shijiazhuang 050071 Hebei, China.
² School of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang 050024 Hebei, China.
³ Graduate School of Hebei Medical University, Shijiazhuang 050017 Hebei, China.
⁴ Chengde Medical University, Chengde 067000 Hebei, China.
⁵ College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801 Shanxi, China.
⁶ College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801 Shanxi, China; Center of Experiment Teaching, Shanxi Agricultural University, Taigu 030801 Shanxi, China; College of Life Science, Shanxi Agricultural University, Taigu 030801 Shanxi, China.
⁷ Hebei Key Laboratory of Reproductive Medicine, Hebei Reproductive Health Hospital, Shijiazhuang 050071 Hebei, China; School of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang 050024 Hebei, China; Graduate School of Hebei Medical University, Shijiazhuang 050017 Hebei, China; Chengde Medical University, Chengde 067000 Hebei, China. Electronic address: wshsong@126.com.
⁸ College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801 Shanxi, China. Electronic address: rdulab@163.com.

PMID: 41386050
DOI: 10.1016/j.envint.2025.109975

Abstract

Bisphenol A (BPA), a common environmental endocrine disruptor, has been shown to adversely affect male reproductive function. However, the mechanisms of reproductive impairment in both BPA-exposed males (F0) and their unexposed offspring (F1) remain unclear. Furthermore, there are currently no reports on that paternal Zinc (Zn) and/or Selenium (Se) supplementation ameliorate BPA-induced and transgenerational reproductive damage in F0 and F1, respectively. This study aimed to address these scientific issues by integrating transcriptomics and metabolomics. Our results revealed that BPA induced reproductive damage of F0 by altering the transport and homeostasis of Zn and Se, disrupting the synthesis and transformation balances of testosterone (T) and estradiol (E2), and increasing the oxidative stress and apoptosis levels. Furthermore, most of the changes of F0 was transmitted to F1 generation, causing reproductive damage to the male offspring. In contrast, supplementing with Zn and/or Se for F0 could alleviate these impacts of BPA on F0 and F1. Notably, the combination of Zn and Se was generally more effective compared to individual supplementation. The transcriptomics and metabolomics analyses revealed the overall mechanisms of Zn and/or Se alleviating BPA-induced testicular damage in F0 and F1 male mice. The reason why Zn and Se combined is superior to Zn or Se alone is related to their unique or additive regulatory roles on the oxidative phosphorylation pathway and antioxidant functions, which exhibits the characteristic of intergenerational transmission in male mice.

Keywords: Bisphenol A; Offspring; Reproductive injury; Selenium; Zinc.