Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy

The role of ovarian steroid and pregnancy hormones

David W Greening, Hong Nguyen, Jemma Evans, Richard Simpson, Lois Adrienne Salamonsen

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)99 - 112
Number of pages14
JournalJournal of Proteomics
Volume144
DOIs
Publication statusPublished - 2 Jun 2016

Keywords

  • Embryo implantation
  • Secretome
  • Pregnancy
  • Endometrium
  • Proteomics
  • Uterine microenvironmen
  • Estrogen
  • Progesterone
  • hCG
  • Trophoblast
  • Blastocyst
  • Receptivity

Cite this

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title = "Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy: The role of ovarian steroid and pregnancy hormones",
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.",
keywords = "Embryo implantation, Secretome, Pregnancy, Endometrium, Proteomics, Uterine microenvironmen, Estrogen, Progesterone, hCG, Trophoblast, Blastocyst, Receptivity",
author = "Greening, {David W} and Hong Nguyen and Jemma Evans and Richard Simpson and Salamonsen, {Lois Adrienne}",
year = "2016",
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Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy : The role of ovarian steroid and pregnancy hormones. / Greening, David W; Nguyen, Hong; Evans, Jemma; Simpson, Richard; Salamonsen, Lois Adrienne.

In: Journal of Proteomics, Vol. 144, 02.06.2016, p. 99 - 112.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy

T2 - The role of ovarian steroid and pregnancy hormones

AU - Greening, David W

AU - Nguyen, Hong

AU - Evans, Jemma

AU - Simpson, Richard

AU - Salamonsen, Lois Adrienne

PY - 2016/6/2

Y1 - 2016/6/2

N2 - 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.

AB - 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.

KW - Embryo implantation

KW - Secretome

KW - Pregnancy

KW - Endometrium

KW - Proteomics

KW - Uterine microenvironmen

KW - Estrogen

KW - Progesterone

KW - hCG

KW - Trophoblast

KW - Blastocyst

KW - Receptivity

UR - http://www.ncbi.nlm.nih.gov/pubmed/27262222

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DO - 10.1016/j.jprot.2016.05.026

M3 - Article

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JO - Journal of Proteomics

JF - Journal of Proteomics

SN - 1874-3919

ER -