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Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy the role of ovarian steroid and pregnancy hormones.pdf (418.08 kB)

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

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posted on 12.08.2021, 06:32 by David GreeningDavid Greening, HPT Nguyen, J Evans, Richard SimpsonRichard Simpson, LA Salamonsen
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.

Funding

This work was supported, in part, by the National Health and Medical Research Council (NHMRC) of Australia project grant #1057741 (LAS, RJS), the Victorian Government's Operational Infrastructure Support Program funding, an NHMRC Fellowship #1002028 (LAS), La Trobe Institute for Molecular Science Fellowship (DWG), and La Trobe University Leadership RFA Grant (DWG). We particularly thank the patients who provided consent for use of their endometrial tissue and Sister Judi Hocking for its collection. We acknowledge Dr. Tracey Edgell for her contribution in providing additional proteomic data for comparison purposes. We acknowledge the La Trobe University-Comprehensive Proteomics Platform for providing infrastructure and expertise.

History

Publication Date

01/01/2016

Journal

Journal of Proteomics

Volume

144

Pagination

14p. (p. 99-112)

Publisher

Elsevier

ISSN

1874-3919

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.