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



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.
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia. Electronic address: d.greening@latrobe.edu.au.
David W
DW
Greening
Hudson Institute of Medical Research (previously Prince Henry's Institute), Clayton, Victoria 3168, Australia. Electronic address: hong.nguyen@hudson.org.au.
Hong P T
HP
Nguyen
Hudson Institute of Medical Research (previously Prince Henry's Institute), Clayton, Victoria 3168, Australia.
Jemma
J
Evans
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
Richard J
RJ
Simpson
Hudson Institute of Medical Research (previously Prince Henry's Institute), Clayton, Victoria 3168, Australia.
Lois A
LA
Salamonsen
D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects; D004622:Embryo, Mammalian; D047108:Embryonic Development; D004717:Endometrium / Q000166:cytology*; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D010053:Ovary / Q000502:physiology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology; D020543:Proteome / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism
D006063:Chorionic Gonadotropin; D012739:Gonadal Steroid Hormones; D011257:Pregnancy Proteins; D020543:Proteome; D011374:Progesterone
Blastocyst; Embryo implantation; Endometrium; Estrogen; Pregnancy; Progesterone; Proteomics; Receptivity; Secretome; Trophoblast; Uterine microenvironment; hCG