TY - JOUR
T1 - Chronic exposure to bisphenol a affects uterine function during early pregnancy in mice
AU - Li, Quanxi
AU - Davila, Juanmahel
AU - Kannan, Athilakshmi
AU - Flaws, Jodi A.
AU - Bagchi, Milan K.
AU - Bagchi, Indrani C.
N1 - Publisher Copyright:
Copyright © 2016 by the Endocrine Society.
PY - 2016/5
Y1 - 2016/5
N2 - Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plasticsandepoxy resins, has receivedmuchattention in female reproductive healthdue to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study,weaddressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene,HAND2(heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy.
AB - Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plasticsandepoxy resins, has receivedmuchattention in female reproductive healthdue to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study,weaddressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene,HAND2(heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy.
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U2 - 10.1210/en.2015-2031
DO - 10.1210/en.2015-2031
M3 - Article
C2 - 27022677
AN - SCOPUS:84969753199
SN - 0013-7227
VL - 157
SP - 1764
EP - 1774
JO - Endocrinology
JF - Endocrinology
IS - 5
ER -