title: A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound.
abstract: Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical, and one of the major new issues is the safe replacement of this commonly used compound. Bisphenol S (BPS) and bisphenol F (BPF) are already or are planned to be used as BPA alternatives. With the use of a culture system that we developed (fetal testis assay [FeTA]), we previously showed that 10 nmol/L BPA reduces basal testosterone secretion of human fetal testis explants and that the susceptibility to BPA is at least 100-fold lower in rat and mouse fetal testes. Here, we show that addition of LH in the FeTA system considerably enhances BPA minimum effective concentration in mouse and human but not in rat fetal testes. Then, using the FeTA system without LH (the experimental conditions in which mouse and human fetal testes are most sensitive to BPA), we found that, as for BPA, 10 nmol/L BPS or BPF is sufficient to decrease basal testosterone secretion by human fetal testes with often nonmonotonic dose-response curves. In fetal mouse testes, the dose-response curves were mostly monotonic and the minimum effective concentrations were 1,000 nmol/L for BPA and BPF and 100 nmol/L for BPS. Finally, 10,000 nmol/L BPA, BPS, or BPF reduced Insl3 expression in cultured mouse fetal testes. This is the first report describing BPS and BPF adverse effects on a physiologic function in humans and rodents.
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
authors.forename: Soria
authors.initials: S
authors.lastname: Eladak
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
authors.forename: Tiphany
authors.initials: T
authors.lastname: Grisin
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Moison
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
authors.forename: Marie-Justine
authors.initials: MJ
authors.lastname: Guerquin
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: N'Tumba-Byn
authors.affiliation: Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital A. Béclère, Université Paris Sud, Clamart, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pozzi-Gaudin
authors.affiliation: Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital A. Béclère, Université Paris Sud, Clamart, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benachi
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Livera
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Rouiller-Fabre
authors.affiliation: Unit of Genetic Stability, Stem Cells, and Radiation, Laboratory of Development of the Gonads, Université Paris Diderot, Sorbonne Paris Cité, Fontenay-aux-Roses, France; Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; Institut National de la Santé et de la Recherche Médicale, Unité 967, Fontenay-aux-Roses, France. Electronic address: rene.habert@cea.fr.
authors.forename: René
authors.initials: R
authors.lastname: Habert
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D057915:Drug Substitution / Q000009:adverse effects / Q000379:methods; D052244:Endocrine Disruptors / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D051381:Rats; D018570:Risk Assessment; D013045:Species Specificity; D013450:Sulfones / Q000633:toxicity*; D013737:Testis / Q000187:drug effects* / Q000196:embryology*; D000098831:Bisphenol S Compounds; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004852:Epoxy Compounds; D010636:Phenols; D013450:Sulfones; C543008:bisphenol S; D000098831:Bisphenol S Compounds; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C423722:bisphenol F diglycidyl ether
keywords: BPA; BPF; BPS; Bisphenol A; Insl3; Leydig cells; bisphenol F; bisphenol S; endocrine disruptors; environmental health; fetus; human; organotypic culture; species differences; testis; testosterone