Chronic exposure to bisphenol a affects uterine function during early pregnancy in mice

Quanxi Li, Juanmahel Davila, Athilakshmi Kannan, Jodi A. Flaws, Milan K. Bagchi, Indrani C. Bagchi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1764-1774
Number of pages11
JournalEndocrinology
Volume157
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

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Pregnancy
Progesterone Receptors
polycarbonate
Fibroblast Growth Factors
Environmental Exposure
Pregnancy Maintenance
Habitual Abortion
bisphenol A
Neural Crest
Poisons
Occupational Exposure
Stromal Cells
Infertility
Down-Regulation
Epithelium
Genes
Therapeutics

ASJC Scopus subject areas

  • Endocrinology

Cite this

Li, Q., Davila, J., Kannan, A., Flaws, J. A., Bagchi, M. K., & Bagchi, I. C. (2016). Chronic exposure to bisphenol a affects uterine function during early pregnancy in mice. Endocrinology, 157(5), 1764-1774. https://doi.org/10.1210/en.2015-2031

Chronic exposure to bisphenol a affects uterine function during early pregnancy in mice. / Li, Quanxi; Davila, Juanmahel; Kannan, Athilakshmi; Flaws, Jodi A.; Bagchi, Milan K.; Bagchi, Indrani C.

In: Endocrinology, Vol. 157, No. 5, 01.05.2016, p. 1764-1774.

Research output: Contribution to journalArticle

Li, Q, Davila, J, Kannan, A, Flaws, JA, Bagchi, MK & Bagchi, IC 2016, 'Chronic exposure to bisphenol a affects uterine function during early pregnancy in mice', Endocrinology, vol. 157, no. 5, pp. 1764-1774. https://doi.org/10.1210/en.2015-2031
Li Q, Davila J, Kannan A, Flaws JA, Bagchi MK, Bagchi IC. Chronic exposure to bisphenol a affects uterine function during early pregnancy in mice. Endocrinology. 2016 May 1;157(5):1764-1774. https://doi.org/10.1210/en.2015-2031
Li, Quanxi ; Davila, Juanmahel ; Kannan, Athilakshmi ; Flaws, Jodi A. ; Bagchi, Milan K. ; Bagchi, Indrani C. / Chronic exposure to bisphenol a affects uterine function during early pregnancy in mice. In: Endocrinology. 2016 ; Vol. 157, No. 5. pp. 1764-1774.
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