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Updated: Dec 4, 2025
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Bisphenol A exposure increases epididymal susceptibility to infection in mice
Yoo-Jin Park1, Won-Ki Pang1, Do-Yeal Ryu1
1Department of Animal Science & Technology and BET Research Institute, Chung-Ang University, Anseong, Gyeonggi-do 17546, Republic of Korea.
Abstract:
Male fertility is linked with several well-orchestrated events including spermatogenesis, epididymal maturation, capacitation, the acrosome reaction, fertilization, and beyond. However, the detrimental effects of bisphenol A (BPA) on sperm maturation compared to spermatogenesis and sperm cells remain unclear. Therefore, this study was to investigate whether pubertal exposure to BPA induces male infertility via interruption of the immune response in the epididymis. CD-1 male mice (5 weeks old) were treated daily with vehicle (corn oil) and 50 mg BPA/kg-BW for 6 weeks by oral gavage. Following BPA exposure, we observed decreased intraepithelial projection of basal cells, indicative of changes to the luminal environment. We also observed decreased projection of macrophages and protrusion of apoptotic cells into the lumen induced by incomplete phagocytosis of apoptotic cells in the caput epididymis. Exposure to BPA also reduced the anti- and pro-inflammatory cytokines IL-10, IL-6, IFN-γ, and IL-7 in the epididymis, while the chemotaxis-associated cytokines CCL12, CCL17, CXCL16, and MCP-1 increased. This study suggests two possible mechanisms for BPA induction of male infertility. First, exposure to BPA may induce an imbalance of immune homeostasis by disrupting the ability of basal cells to perceive environmental changes. Second, exposure to BPA may lead to collapse of macrophage phagocytosis via downregulation of intraepithelial projection and inflammatory-related cytokines. In conclusion, the observed potential pathways can lead to autoimmune disorders such epididymitis and orchitis.
Insights
Pubertal exposure to bisphenol A (BPA) disrupts the epididymis immune response in male mice, impairing sperm maturation and potentially causing infertility. BPA interferes with macrophage function and cytokine balance, leading to autoimmune disorders.
Area of Science:
- Reproductive Biology
- Environmental Toxicology
- Immunology
Background:
- Male fertility relies on complex events like spermatogenesis and sperm maturation.
- The impact of bisphenol A (BPA) on sperm maturation, compared to spermatogenesis, is not fully understood.
- Investigating BPA's effects on the epididymis immune response is crucial for understanding male infertility.
Purpose of the Study:
- To determine if pubertal exposure to BPA causes male infertility by disrupting the epididymis immune response.
- To elucidate the mechanisms by which BPA affects immune homeostasis in the male reproductive tract.
Main Methods:
- CD-1 male mice were exposed to BPA (50 mg/kg-BW) or vehicle daily for 6 weeks via oral gavage.
- Evaluated changes in the epididymal luminal environment, including basal cell projections and macrophage activity.
- Analyzed alterations in key inflammatory and chemotaxis-associated cytokines within the epididymis.
Main Results:
- BPA exposure decreased basal cell projections and macrophage activity in the epididymis.
- Observed incomplete phagocytosis of apoptotic cells in the epididymis lumen.
- Detected significant changes in cytokine profiles, with reduced anti- and pro-inflammatory cytokines (IL-10, IL-6, IFN-γ, IL-7) and increased chemotaxis-associated cytokines (CCL12, CCL17, CXCL16, MCP-1).
Conclusions:
- BPA exposure may induce male infertility by disrupting immune homeostasis in the epididymis.
- Potential mechanisms include impaired environmental sensing by basal cells and compromised macrophage phagocytosis.
- These disruptions can potentially lead to autoimmune conditions such as epididymitis and orchitis.
