An exaggerated epinephrine-adrenergic receptor signaling impairs uterine decidualization in mice

Reprod Toxicol. 2019 Dec:90:109-117. doi: 10.1016/j.reprotox.2019.09.003. Epub 2019 Sep 11.

Abstract

Our understanding of the relationship between stress-derived epinephrine and early pregnancy failure remains incomplete. Here, we explored the effect of epinephrine exposure on early pregnancy and pseudopregnancy in mice. Increased expression of adrenergic receptors Adra1b, Adra2b and Adrb2 was observed during decidualization and post-implantation embryogenesis was delayed or survival impaired. Epinephrine treatment also impaired decidualization in both the gravid and pseudopregnant uterus, suggesting the effect on decidualization was independent of the conceptus. This included a suppression of endometrial stroma cell proliferation and of key decidualization regulators, including COX2, BMP2 and WNT4. Collectively, these data demonstrate that maternal epinephrine exposure during early pregnancy impairs uterine decidualization and embryo development, underlying early pregnancy failure.

Keywords: Decidualization; Epinephrine; Pregnancy failure; Stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agonists / toxicity*
  • Animals
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Embryonic Development / drug effects
  • Epinephrine / toxicity*
  • Female
  • Mice
  • Pregnancy
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic / genetics*
  • Signal Transduction / drug effects
  • Stromal Cells / drug effects
  • Stromal Cells / pathology
  • Uterus / drug effects*
  • Uterus / metabolism
  • Uterus / pathology
  • Wnt4 Protein / metabolism

Substances

  • Adrenergic Agonists
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • RNA, Messenger
  • Receptors, Adrenergic
  • Wnt4 Protein
  • Wnt4 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Epinephrine