Effects of Preimplantation Bisphenol-A (BPA) Exposure on Preimplantation Embryo Development and Transport and Uterine Receptivity in Mice.

Abstract

Bisphenol A (BPA) is an endocrine disruptor widely used in polycarbonate plastics and epoxy resins. It has been reported that BPA has adverse effects on uterine development: it alters uterine expression of progesterone and estrogen receptors; and BPA at ~400 mg/kg is detrimental to embryo implantation. Embryo implantation is a synchronized process between a competent embryo and a receptive uterus. Uterine receptivity is a hormone-controlled transient state in which the uterus can accept an embryo to implant. The mechanism of BPA in disrupting embryo implantation is currently unknown. To investigate the potential effects of BPA on preimplantation embryos and uterine receptivity, timed pregnant wild type C57BL6 young adult females were treated with 0, 10, 40, and 100 mg/kg BPA subcutaneously daily from gestation day 0.5 to day 3.5, and detected for implantation sites on gestation day 4.5. No implantation sites were detected on gestation day 4.5 but retention of embryos in the oviduct and delayed embryo development were detected on day 3.5 in the 100 mg/kg/day BPA-treated females, indicating the detrimental effects of 100 mg/kg/day BPA on embryo transport and preimplantation embryo development. When untreated healthy embryos were transferred to pseudopregnant females treated with 100 mg/kg/day BPA from gestation day 0.5 to 3.5, no implantation sites were detected on day 4.5, indicating that 100 mg/kg/day BPA can also adversely affect uterine receptivity. Delayed implantation and prolonged gestation period, and increased perinatal lethality were detected in the 40 mg/kg/day BPA-treated females and their offspring, respectively. Progesterone receptor (PR), which disappears from uterine luminal epithelium (LE) upon embryo implantation, remained highly expressed in the LE of pregnant day 4.5 uteri from 40 and 100 mg/kg BPA-treated mice, further demonstrating defective embryo implantation in these BPA-treated mice. Normal implantation was observed in the 10 mg/kg/day BPA-treated females or the female offspring from 40 mg/kg/day BPA-treated group. These data demonstrate that preimplantation BPA exposure at 40 and 100 mg/kg/day can adversely affect embryo implantation. (Supported by University of Georgia and NIH R15HD066301) (poster)