Bisphenol A-induced testicular immune dysfunction leads to suppressed steroidogenesis and excessive histamine production.

Bisphenol A (BPA), as environmentally ubiquitous endocrine-disrupting chemical, adversely affects the male reproductive system, contributing to male infertility. The effects of BPA on the immunological mechanisms in the testis associated with testicular immune privileges and steroidogenesis, are less studied. Therefore, this study aimed to investigate the potential impact of BPA on immunological mechanisms in the testis that are critical for male fertility. Five-week-old male CD-1 mice (30 mice/ group) were divided into control (corn oil), no observed adverse effects level (NOAEL, 5 mg/kg -BW), and lowest-observed adverse effects level (LOAEL, 50 mg/kg -BW) groups. BPA was orally administered for six weeks, beginning at the onset of puberty (five-week-old) and continuing through the entire period of puberty until ten-week-old. In the LOAEL group, expression of protease activated receptor 2 was increased by mast cell tryptase activation, which promoted fibroblast proliferation in the LOAEL group. Additionally, we observed that α-smooth muscle actin expression, a marker of myofibroblast activation, was increased in the LOAEL group. Additionally, collagen accumulation was observed in the seminiferous tubules adjacent to the blood vessels. This resulted in increased testicular germ cell apoptosis along with decreased sperm concentration and motility in the LOAEL group. BPA exposure also led to excessive mast cell activation and histamine overproduction, which resulted in reduced expression of steroidogenic enzymes and decreased testosterone levels. In conclusion, this study highlighted that the role of BPA in male infertility by disrupting testicular immune cell composition, which impaired spermatogenesis and steroidogenesis, creating an unsuitable environment for germ cells.