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.
Highlights
The implantation of a blastocyst into a receptive uterus is part of a multifaceted process that includes embryo implantation, decidualization, and vascular modification [1,2], which are key events in the establishment of a successful pregnancy, and the success of each event is a prerequisite for advancement to the stage
We reported that the calcium ion influx genes TRPV5 and TRPV6 are expressed in the uterine endometrial region, while the calcium ion efflux genes Na+ /Ca2+ exchanger 1 (NCX1) and Plasma membrane Ca2+ -ATPase 1 (PMCA1) were detected in the basolateral membranes of the uterus [25]
Number of Statistical implantation sites in performed on the combined data from gestation day (GD) 5.5 showed that the number of implantation sites in pregnant mice treated with OP (100 mg/kg) from GD 0.5 to GD 3.5 was significantly lower than that in pregnant mice treated with OP (100 mg/kg) from GD 0.5 to GD 3.5 was significantly lower than that
Summary
The implantation of a blastocyst into a receptive uterus is part of a multifaceted process that includes embryo implantation, decidualization, and vascular modification [1,2], which are key events in the establishment of a successful pregnancy, and the success of each event is a prerequisite for advancement to the stage. Blastocyst implantation occurs within a limited period when blastocyst competency is coordinated with the receptivity of the uterus. Any disturbance of this coordination can induce unsuccessful or flawed implantation. Progesterone and estrogen are the principal hormones that directly affect uterine receptivity, acting through nuclear estrogen (ERα) and progesterone receptor (PR) [1]. Both E2 and PR can regulate the production of cytokines, growth factors, homeobox transcription factors, and cyclooxygenasederived prostaglandins. These factors are crucial during uterine preparation for implantation and
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