Polybrominated diphenylethers (PBDEs) act as apoptotic factors in the corpus luteum in addition to having a short-term stimulatory effect on progesterone secretion by luteal cells

Abstract

To the best of our knowledge, there is a lack of data showing effect of polybrominated diphenyl ethers (PBDEs) on the corpus luteum (CL), a mini-endocrine gland responsible for a normal estrous cycle and the maintenance of pregnancy. Luteal cells obtained from corpora lutea (8–10 days after ovulation) were exposed to PBDE 47, 99, and 100 at doses of 50, 250, and 500 ng/ml for 24 and 48 hours. The progesterone (P4) level in the culture medium and caspase-3, -8, and -9 activities in the cells were estimated by ELISA. CYP11A1 and 3β-HSD protein expression were evaluated by western blot. A 2-fold increase in P4 secretion after 24 hours and no effect after 48 hours of exposure were observed. We demonstrated that the increase in P4 secretion was the result of the stimulatory action of all PBDEs on 3β-HSD protein expression and additionally, PBDE 99 alone on 3β-HSD activity (measured by the conversion of P5 into P4). In contrast, the activation of caspase-8 and -9 but not caspase-3 during 24 hours of exposure, and activation of all investigated caspases during 48 hours was observed. In conclusion, the present findings provide evidence that despite the initial stimulatory effect of PBDEs on the secretion of progesterone (due to the fact that the biochemical apparatus responsible for the conversion of cholesterol into pregnenolone remains uninterrupted). PBDEs are also a key executor of apoptosis (by activating both the extrinsic and intrinsic pathways of apoptosis after longer exposure periods) which can lead to premature dysfunction of the corpus luteum.

Keywords::

• PBDEs
• progesterone
• CYP11A1
• 17β-HSD
• caspase-3
• -8 and -9
• luteal cells