塑化劑酚甲烷Bisphenol A (BPA) 是已知的內分泌干擾素
會干擾卵子顆粒細胞之雌激素&黃體素之合成進而影響懷孕率

Hum Reprod. 2016 Apr 24. pii: dew088. [Epub ahead of print]

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

Mansur A1, Adir M1, Yerushalmi G1, Hourvitz A1, Gitman H1, Yung Y1, Orvieto R1, Machtinger R2.

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Abstract

STUDY QUESTION:

Does Bisphenol A (BPA) impair steroid hormone production in human luteinized granulosa cells in vitro?

SUMMARY ANSWER:

At supra-physiological concentrations, BPA alters 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 BPA exposure 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 from 44 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 µg/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 µg/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 µg/ml of BPA (P < 0.001). These concentrations also significantly reduced the mRNA levels of 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP11A1 and CYP19A1 without affecting StAR and 17β-hydroxysteroid dehydrogenase mRNA expression. Similarly, 3β-HSD, CYP11A1 and CYP19A1 protein levels were reduced after administration of 20 µg/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.