20.500.12556/DiRROS-24113 Bisphenol a disrupts steroidogenesis and induces apoptosis in human granulosa cells cultured in vitro Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 µM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 µM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 µM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA’s concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations. bisphenol A human granulosa cells steroidogenesis apoptosis steroid hormones true false true Angleški jezik Ni določen Neznano 2025-11-13 10:52:35 2025-11-13 10:52:36 2025-11-14 03:41:04 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 9. 6. 2025; str. 1-21 iss. 9 [article no.] 4081 Vol. 26 2025 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 617.7 1422-0067 10.3390/ijms26094081 238749955 RAZ_Celar_Sturm_Dominika_2025.pdf RAZ_Celar_Sturm_Dominika_2025.pdf 1 8E85A0D518D500E85A31BDB603E5056C 5cb26a97cf08135f5ac5f5eba0b23ea5955d8bfdb0737280930adceb2ebd9432 a02fcb5f-c076-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35873 https://www.mdpi.com/1422-0067/26/9/4081 1 7dbb868e-c076-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35872 Univerzitetni klinični center Ljubljana 0 0 0