Cumulative and potential synergistic effects of seven different bisphenols on human granulosa cells in vitro?
2023
Lebachelier de la Riviere, Marie-Emilie | Wu, Luyao | Gayet, Manon | Bousquet, Marie | Buron, Charlotte | Vignault, Claire | Téteau, Ophélie | Desmarchais, Alice | Maillard, Virginie | Uzbekova, Svetlana | Guérif, Fabrice | Lacroix, Marlène | Papillier, Pascal | Jarrier-Gaillard, Peggy | Binet, Aurélien | Elis, Sebastien | Physiologie de la reproduction et des comportements [Nouzilly] (PRC) ; Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | CHRU de Tours, Service de Médecine et Biologie de la Reproduction-CECOS, Tours, France | Innovations Thérapeutiques et Résistances (InTheRes) ; Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Université de Poitiers - Faculté de Médecine et de Pharmacie ; Université de Poitiers | Service de Pédiatrie, CHUR Poitiers | ANR-18-CE34-0011,MAMBO,Impact du métabolisme sur les effets ovariens du bisphenol S(2018)
Bisphenol (BP) structural analogues of BPA are widely used. Previous studies showed similar effects of BPA and BPS on reproduction in several species including human. We hypothesised that the similar effects of several bisphenols (BPs) could accumulate in granulosa cells (GCs) and affects steroidogenesis. This study investigated the effects of seven BP analogues and their equimolar cocktail on human granulosa cells (hGC) and assessed BPA, BPS, BPF and BPAF level exposures in the follicular fluid of 277 women undergoing Assisted Reproductive Technology. The hGCs were recovered after women oocyte punctures and treated with the seven BP analogues (BPS, BPA, BPAF, BPF, BPAP, BPE and BPB) or their equimolar cocktail of 7 × 1.43 or 7 × 7.14 μM for each of the seven BPs, the sum of BPs reaching 10 ("∑BPs 10 μM"), or 50 μM ("∑BPs 50 μM"), respectively. Oestradiol and progesterone secretion, cell proliferation, viability and expression of steroidogenic enzymes were investigated. Progesterone secretion was decreased by 6 BPs 10 μM and the cocktail "∑BPs 10 μM", (-17.8 to -41.3%) and by all seven BPs 50 μM and "∑BPs 50 μM" (-21.8 to -84.2%). Oestradiol secretion was decreased only by 50 μM BPAF and BPAP (-37.8% and -44%, respectively), with corresponding decreases in CYP17A1 and CYP19A1 gene expression. Cellular proliferation was decreased after treatment with 50 μM BPAF (-32.2%), BPAP (-29%), BPB (-24%) and the equimolar cocktail "∑BPs 50 μM" (-33.1%). BPB (50 μM) and the cocktail "∑BPs 50 μM" increased HSD3B2 mRNA expression. At least one BP was detected in 64 of 277 (23.1%) women follicular fluids. Similar effects of the seven BPs or their cocktail were observed on progesterone secretion and/or on cell proliferation, suggesting cumulative effects of BPs. Our results highlight the urge to consider all BPs simultaneously and to further investigate the potential additive or synergistic effects of several BPs.
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