Does BPA alter steroid hormone synthesis in human granulosa cells in vitro?

Abdallah Mansur, Michal Adir, Gil Yerushalmi, Ariel Hourvitz, Hila Gitman, Yuval Yung, Raoul Orvieto, Ronit Machtinger

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Study question: Does Bisphenol A (BPA) impair steroid hormone production in human luteinized granulosa cells in vitro? summaryanswer: At supra-physiological concentrations, BPAalters progesterone and estradiol synthesis in vitro and significantly reduces the mRNA and protein expression levels of three genes encoding steroidogenesis enzymes. what is known already: In IVF patients, the effects of BPAexposure on cycle outcome are controversial. Previous animal studies have shown that granulosa cell steroid hormone synthesis is compromised after BPA exposure, but their findings have been difficult to replicate in humans due, in part, to the low availability of discarded biological material. study design, size, duration: Luteinized granulosa cells obtained from44 fertile and infertile patients undergoing in vitro fertilization were cultured for 48 h with different concentrations of BPA (0, 0.2, 0.02, 2.0, 20 mg/ml). participants/materials, setting, methods: Culture medium and total RNA extracted from the luteinized granulosa cells were examined for estradiol and progesterone levels as well as mRNA and protein expression of steroidogenesis enzymes, using enzyme immunoassays, real-time PCR and western blots. main results and the role of chance: Treatment of granulosa cells with 2 or 20 mg/ml BPA for 48 h resulted in significantly lower progesterone biosynthesis (P < 0.005 and <0.001, respectively). Estradiol production was significantly altered only after incubation with 20 mg/ml of BPA (P < 0.001). These concentrations also significantly reduced the mRNA levels of 3b-hydroxysteroid dehydrogenase (3b-HSD), CYP11A1 and CYP19A1 without affecting StAR and 17b-hydroxysteroid dehydrogenase mRNA expression. Similarly, 3b-HSD, CYP11A1 and CYP19A1 protein levels were reduced after administration of 20 mg/ml BPA. Lower BPA concentrations similar to, and up to 100 times, the concentrations measured in human follicular fluid, serum and urine did not alter steroidogenesis in primary granulosa cell cultures. limitations, reasons for caution: This was an in vitro study investigating the effects of acute exposure (48 h) of BPA on discarded material. As such, the model may not accurately reflect the effect of BPA on the physiological events of follicular steroid hormone synthesis in vivo. wider implications of the findings: Our results showthat in vitro exposure to BPA at lowdoses does not affect granulosa cells steroidogenesis. Combined with recent in vivo studies, these data can be reassuring but further studies are needed to assess the effects of chronic exposure to BPA on ovarian steroidogenesis. study funding and competing interest(s): This study was supported by grant number 1936/12 from the Israeli Science Foundation (ISF). The authors have no conflict of interest.

Original languageEnglish
Pages (from-to)1562-1569
Number of pages8
JournalHuman Reproduction
Issue number7
StatePublished - 1 Jul 2016
Externally publishedYes


  • Bisphenol A
  • Estradiol
  • Mural cell granulosa
  • Progesterone
  • Steroidogenesis

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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