Fluornen-9-bisphenol increases Leydig cell proliferation but inhibits maturation in pubertal male rats via interacting with androgen receptor as an antagonist and estrogen receptor α as an agonist

Fluornen-9-bisphenol (BPFL) is used as one of the alternatives for bisphenol A. However, whether BPFL has deleterious effects to the male reproductive system and the underlying mechanism remain unknown. Here, we report the effects of BPFL on Leydig cell development in male rats in puberty. Male Sprague-Dawley (28 days old) rats were dosed with 0, 10, 100, 200 mg/kg/day BPFL via gavage for 28 days. BPFL significantly decreased serum testosterone levels at 200 mg/kg while increasing serum luteinizing hormone and follicle-stimulating hormone levels at 200 mg/kg. BPFL markedly increased Leydig cell number but down-regulated the expression of CYP17A1 and its protein level in Leydig cells at 200 mg/kg. Further study showed that BPFL significantly increased Pcna and CDK2 expression and increased Leydig cell proliferation at 200 mg/kg. BPFL treatment to immature Leydig cells isolated from 28-day-old male rats for 24 h significantly inhibited testosterone biosynthesis at 50 μM, which was completely reversed by the Androgen Receptor agonist 7α-methyl-nortestosterone and Estrogen Receptor α antagonist ICI 182,780. In conclusion, BPFL increases Leydig cell proliferation but inhibits its maturation in male rats in puberty by blocking Androgen Receptor and activating Estrogen Receptor α.