Effects of Bisphenol A and 4-tert-Octylphenol on Embryo Implantation Failure in Mouse

Abstract

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all human miscarriage cases. Calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2, ICI and EDs + ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in utero. Meanwhile, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in the uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

4-tert-Octylphenol Exposure Disrupts Brain Development and Subsequent Motor, Cognition, Social, and Behavioral Functions

“…Specific pathogen-free C57BL/6J male and female mice (8 weeks old, 25–30 g) were obtained from Samtaco (Osan, Gyeonggi, Republic of Korea). The mice were housed in polycarbonate cages under controlled environment conditions as in previous [ 11 ]. After the acclimatization period, female mice were mated with male mice overnight at a proportion of 2 : 1, and the presence of a vaginal plug was set as embryonic day (E) 0.5.…”

The Endocrine Disruptor Bisphenol A (BPA) Affects the Enteric Neurons Immunoreactive to Neuregulin 1 (NRG1) in the Enteric Nervous System of the Porcine Large Intestine

“…In the reproductive system BPA causes changes in the uterus manifested by the increase in the thickness of the endometrium and number of fibroblasts, as well as by the inhibition of apoptosis [ 43 , 44 ]. These changes are accompanied by disturbances in estrus cycle, embryo implantation after fertilization, motor activity of the uterus, sex hormones levels and secretion of active substances by nervous structures supplying the uterine [ 45 , 46 , 47 , 48 ]. Exposure to BPA may contribute to development of endometriosis and cervical cancer [ 49 , 50 ].…”

Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation: A Systematic Review of 34 Mouse Model Studies

“…The analysis of the association of BPA with the pregnancy rate and the number of implantation sites in murine studies were analyzed in 16 available papers [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. These studies differentiated for exposure dosage and administration period.…”