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

Reproductive Toxicity and Teratogenicity of Fluorene-9-bisphenol on Chinese Medaka (Oryzias sinensis): A Study from Laboratory to Field

“…Toxicological studies have reported that BHPF has multiple toxicities on mammals and aquatic animals. Experimental studies on mice found that BHPF could induce changes in reproductive and hepatic tissues in female, reduce birth weight and implantation site weight in pregnancy, and cause obvious emotional behavior changes, stillbirth, and abortion. ,− Meng et al reported that BHPF could decrease serum testosterone levels and increase the Leydig cell number and serum luteinizing hormone and follicle-stimulating hormone levels in pubertal male rats . In addition, in vitro studies showed that BHPF could inhibit maturation of mouse oocytes by reducing the protein level of p-MAPK and destroying the meiotic spindle, suppress porcine Sertoli cell proliferation and induce its apoptosis, decrease productions of aldosterone, cortisol, testosterone, and E2 by downregulation of steroidogenic genes in H295R cells through the AC/cAMP/PKA signaling pathway, and prevent proliferation of Ishikawa cells and reduce their migration and invasion abilities by repressing the TGF-beta signaling pathway. ,− Recent studies found that short-term exposure of high BHPF levels to zebrafish (Danio rerio) would induce thyroid-disrupting effects and histopathological alterations in its gill and liver tissues, disrupt myelination by affecting the hypothalamic–pituitary–thyroid axis, decrease the courtship index between female and male, fecundity, and gonadosomatic index, and cause adverse effects in oocyte maturation. − Embryonic or larval zebrafish exposed to BHPF would cause phenotypic malformation, insomnia-like behaviors, severe cardiotoxicity, mild lipid accumulation, retarded epiboly rate and growth, increased mortality, and promoted apoptosis. − However, the potential effects of long-term exposure of BHPF at low levels on fish, as well as those of BHPF contaminations in actual aquatic environments, are little known.…”

“…1,9−11 Meng et al reported that BHPF could decrease serum testosterone levels and increase the Leydig cell number and serum luteinizing hormone and follicle-stimulating hormone levels in pubertal male rats. 12 In addition, in vitro studies showed that BHPF could inhibit maturation of mouse oocytes by reducing the protein level of p-MAPK and destroying the meiotic spindle, suppress porcine Sertoli cell proliferation and induce its apoptosis, decrease productions of aldosterone, cortisol, testosterone, and E2 by downregulation of steroidogenic genes in H295R cells through the AC/cAMP/PKA signaling pathway, and prevent proliferation of Ishikawa cells and reduce their migration and invasion abilities by repressing the TGF-beta signaling pathway. 10,13−16 Recent studies found that short-term exposure of high BHPF levels to zebrafish (Danio rerio) would induce thyroid-disrupting effects and histopathological alterations in its gill and liver tissues, disrupt myelination by affecting the hypothalamic−pituitary−thyroid axis, decrease the courtship index between female and male, fecundity, and gonadosomatic index, and cause adverse effects in oocyte maturation.…”