A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Molecular insights underlying the adverse effects of bisphenol A on gonadal somatic cells' steroidogenic activity
Tekijät: Palak Ewelina, Lebiedzinska Weronika, Lupu Oana, Pulawska Kamila, Anisimowicz S, Mieczkowska Aleksandra N, Sztachelska Maria, Niklinska Gabriella N, Milewska Gabriela, Lukasiewicz Monika, Ponikwicka-Tyszko Donata, Huhtaniemi Ilpo, Wolczynski Slawomir
Kustantaja: ELSEVIER
Julkaisuvuosi: 2023
Journal: Reproductive Biology
Tietokannassa oleva lehden nimi: REPRODUCTIVE BIOLOGY
Lehden akronyymi: REPROD BIOL
Artikkelin numero: 100766
Vuosikerta: 23
Numero: 2
Sivujen määrä: 12
ISSN: 1642-431X
DOI: https://doi.org/10.1016/j.repbio.2023.100766
Verkko-osoite: https://doi.org/10.1016/j.repbio.2023.100766
Bisphenol A (BPA) exposure may impair gonadal steroidogenesis, although the underlying mechanism is not well known. Hereby, we assessed BPA action on human primary granulosa (hGC) and mouse Leydig cells (BLTK-1) proliferation, cytotoxicity, hormone secretion, and steroidogenic enzyme/receptor gene profile. hGC and BLTK-1 cells were stimulated with increasing concentrations of BPA (10-12 M to 10-4 M for cell proliferation assay, 10-8 M to 10-4 M for LDH-cytotoxicity assay, and 10-9 M to 10-5 M for hormone secretion and genes expression analysis). BPA at low concentrations (pM - nM) did not affect cell proliferation in either cell type, although was toxic at higher (mu M) concentrations. BPA stimulation at low nM concentrations decreased the production of estradiol (E2) and testosterone (T) in BLTK-1, E2, and progesterone in hGCs. BPA down-regulated Star, Cyp11a1, and Hsd17b3, but up-regulated Cyp19a1, Esr1, Esr2, and Gpr30 expression in BLTK-1 cells. In hGC, BPA down-regulated STAR, CYP19A1, PGRMC1, and PAQR7 but up-regulated ESR2 expression. Estrogen receptor degrader fulvestrant (FULV) attenuated BPA inhibition of hormone production in both cell lines. FULV also blocked the BPA-induced Gpr30 up-regulation in BLTK-1 cells, whereas in hGC, failed to reverse the down-regulation of PGRMC1, STAR, and CYP19A1. Our findings provide novel mechanistic insights into environmentally-relevant doses of BPA ac-tion through both nuclear estrogen receptor-dependent and independent mechanisms affecting cultured gran-ulosa and Leydig cell steroidogenesis.
