Idiopathic infertility in women is associated with distinct changes in proliferative phase uterine fluid proteins

Harriet Fitzgerald, Jemma Evans, Nicholas Johnson, Giuseppe Infusini, Andrew Ian Webb, Luk Rombauts, Beverley Janine Vollenhoven, Lois Adrienne Salamonsen, Tracey Edgell

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)752-764
Number of pages13
JournalBiology of Reproduction
Volume98
Issue number6
DOIs
Publication statusPublished - Jun 2018

Keywords

  • ECM1
  • Endometrium
  • Infertility
  • Proliferative phase
  • Proteome
  • Uterine fluid

Cite this

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title = "Idiopathic infertility in women is associated with distinct changes in proliferative phase uterine fluid proteins",
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.",
keywords = "ECM1, Endometrium, Infertility, Proliferative phase, Proteome, Uterine fluid",
author = "Harriet Fitzgerald and Jemma Evans and Nicholas Johnson and Giuseppe Infusini and Webb, {Andrew Ian} and Luk Rombauts and Vollenhoven, {Beverley Janine} and Salamonsen, {Lois Adrienne} and Tracey Edgell",
year = "2018",
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language = "English",
volume = "98",
pages = "752--764",
journal = "Biology of Reproduction",
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Idiopathic infertility in women is associated with distinct changes in proliferative phase uterine fluid proteins. / Fitzgerald, Harriet; Evans, Jemma; Johnson, Nicholas; Infusini, Giuseppe; Webb, Andrew Ian; Rombauts, Luk; Vollenhoven, Beverley Janine; Salamonsen, Lois Adrienne; Edgell, Tracey.

In: Biology of Reproduction, Vol. 98, No. 6, 06.2018, p. 752-764.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Idiopathic infertility in women is associated with distinct changes in proliferative phase uterine fluid proteins

AU - Fitzgerald, Harriet

AU - Evans, Jemma

AU - Johnson, Nicholas

AU - Infusini, Giuseppe

AU - Webb, Andrew Ian

AU - Rombauts, Luk

AU - Vollenhoven, Beverley Janine

AU - Salamonsen, Lois Adrienne

AU - Edgell, Tracey

PY - 2018/6

Y1 - 2018/6

N2 - 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.

AB - 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.

KW - ECM1

KW - Endometrium

KW - Infertility

KW - Proliferative phase

KW - Proteome

KW - Uterine fluid

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U2 - 10.1093/biolre/ioy063

DO - 10.1093/biolre/ioy063

M3 - Article

VL - 98

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JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

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