Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy: The role of ovarian steroid and pregnancy hormones

J Proteomics. 2016 Jul 20;144:99-112. doi: 10.1016/j.jprot.2016.05.026. Epub 2016 Jun 2.

Abstract

Dialogue between an appropriately developed embryo and hormonally-primed endometrium is essential to achieve implantation and establish pregnancy. Importantly, the point-of-first-contact between the embryo and the maternal endometrium occurs at the endometrial luminal epithelium (LE). Implantation events occur within the uterine cavity microenvironment regulated by local factors. Defects in embryo-endometrial communication likely underlie unexplained infertility; enhanced knowledge of this communication, specifically at initial maternal-fetal contact may reveal targets to improve fertility. Using a human endometrial luminal-epithelial (LE) cell line (ECC1), this targeted proteomic study reveals unique protein changes in both cellular (98% unique identifications) and secreted (96% unique identifications) proteins in the transition to the progesterone-dominated secretory (receptive) phase and subsequently to pregnancy, mediated by embryo-derived human chorionic gonadotropin (hCG). This analysis identified 157 progesterone-regulated cellular proteins, with further 193 significantly altered in response to hCG. Cellular changes were associated with metabolism, basement membrane and cell connectivity, proliferation and differentiation. Secretome analysis identified 1059 proteins; 123 significantly altered by progesterone, and 43 proteins altered by hCG, including proteins associated with cellular adhesion, extracellular-matrix organization, developmental growth, growth factor regulation, and cell signaling. Collectively, our findings reveal dynamic intracellular and secreted protein changes in the endometrium that may modulate successful establishment of pregnancy.

Biological significance: This study provides unique insights into the developmental biology of embryo implantation using targeted proteomics by identifying endometrial epithelial cellular and secreted protein changes in response to ovarian steroid hormones and pregnancy hormones that are essential for receptivity and implantation.

Keywords: Blastocyst; Embryo implantation; Endometrium; Estrogen; Pregnancy; Progesterone; Proteomics; Receptivity; Secretome; Trophoblast; Uterine microenvironment; hCG.

MeSH terms

  • Cell Line
  • Chorionic Gonadotropin / pharmacology
  • Embryo Implantation / drug effects
  • Embryo, Mammalian
  • Embryonic Development
  • Endometrium / cytology*
  • Epithelial Cells / chemistry
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Gonadal Steroid Hormones / physiology*
  • Humans
  • Ovary / physiology*
  • Pregnancy
  • Pregnancy Proteins / analysis
  • Pregnancy Proteins / drug effects*
  • Pregnancy Proteins / metabolism
  • Pregnancy Proteins / physiology
  • Progesterone / pharmacology
  • Proteome / analysis
  • Proteome / drug effects*
  • Proteome / metabolism

Substances

  • Chorionic Gonadotropin
  • Gonadal Steroid Hormones
  • Pregnancy Proteins
  • Proteome
  • Progesterone