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13 March 2018 Idiopathic infertility in women is associated with distinct changes in proliferative phase uterine fluid proteins
Harriet C. Fitzgerald, Jemma Evans, Nicholas Johnson, Giuseppe Infusini, Andrew Webb, Luk J.R. Rombauts, Beverley J. Vollenhoven, Lois A. Salamonsen, Tracey A. Edgell
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Abstract

The regenerative, proliferative phase of a woman's menstrual cycle is a critical period which lays the foundation for the subsequent, receptive secretory phase. Although endometrial glands and their secretions are essential for embryo implantation and survival, the proliferative phase, when these glands form, has been rarely examined. We hypothesized that alterations in the secreted proteome of the endometrium of idiopathic infertile women would reflect a disturbance in proliferative phase endometrial regeneration. Our aim was to compare the proteomic profile of proliferative phase uterine fluid from fertile (n = 9) and idiopathic infertile (n = 10) women. Proteins with ≥2-fold change (P < 0.05) were considered significantly altered between fertile and infertile groups. Immunohistochemistry examined the endometrial localization of identified proteins. Western immunoblotting defined the forms of extracellular matrix protein 1 (ECM1) in uterine lavage fluid. Proteomic analysis identified four proteins significantly downregulated in infertile women compared to fertile women, including secreted frizzled-related protein 4 (SFRP4), CD44, and ECM1: two proteins were upregulated. Seven proteins were unique to the fertile group and six (including isoaspartyl peptidase/L-asparaginase [ASRGL1]) were unique to the infertile group. Identified proteins were classified into biological processes of tissue regeneration and regulatory processes. ASRGL1, SFRP4, and ECM1 localized to glandular epithelium and stroma, cluster of differentiation 44 (CD44) to stroma and immune cells. ECM1 was present in two main molecular weight forms in uterine fluid. Our results indicate a disturbance in endometrial development during the proliferative phase among infertile women, providing insights into human endometrial development and potential therapeutic targets for infertility.

Summary Sentence

Proteomic analysis of proliferative phase uterine fluid in both fertile and infertile women showed significant differences in the secreted proteins including ECM1 which was further studied for its cellular location and hormonal regulation.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Harriet C. Fitzgerald, Jemma Evans, Nicholas Johnson, Giuseppe Infusini, Andrew Webb, Luk J.R. Rombauts, Beverley J. Vollenhoven, Lois A. Salamonsen, and Tracey A. Edgell "Idiopathic infertility in women is associated with distinct changes in proliferative phase uterine fluid proteins ," Biology of Reproduction 98(6), 752-764, (13 March 2018). https://doi.org/10.1093/biolre/ioy063
Received: 22 December 2017; Accepted: 9 March 2018; Published: 13 March 2018
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