Endocrine-disrupting chemicals (EDCs) have similar structures with steroids hormones, which can interfere with hormone synthesis and normal physiological functions of male and female reproductive organs. Sex steroid hormones influence calcium signaling of the cardiac muscle in early embryo development. Progesterone (P4) has been reported to reduce blood pressure. To confirm the effect of P4, octyl-phenol (OP) and bisphenol A (BPA) on early differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes, P4, OP and BPA were treated at two days after attachment and media were replaced every two days. In addition, mifepristone (RU486) is a synthetic steroid that has an affinity for progesterone receptor (Pgr) and was treated for one day starting on day 11. To investigate the calcium signaling, the expression of calcium channel gene and contraction-related genes was analyzed. Beating ratio was decreased in P4, OP and BPA treatment. The Pgr mRNA level was significantly increased in P4, OP and BPA-treated group. However, the mRNA level of calcium channel gene, Trpv2, was significantly decreased in the P4, OP and BPA-treated group. In addition, expressions of contraction-related genes such as Ryr2, Cam2 and Mlck3 were significantly decreased in the P4, OP and BPA-treated group. Interestingly, treatment of RU486 rescues altered calcium channel gene and contraction-related genes. P4, OP and BPA treatments resulted in the reduction of intracellular calcium level. Taken together, these results suggest that OP and BPA may impact on the inhibition of cardiomyocytes differentiation of mESCs, results in disruption of cardiomyocytes differentiation of mESCs.
18 - 21 May 2019
European Society of Endocrinology