Infertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion
Copyright © 2022 Zhou, Barton, Cui, Santos, Yang, Stern, Kieu, Teh, Ang, Lucky, Sgroi, Ye and Dimitriadis..
Introduction: Embryo implantation failure leads to infertility. As an important approach to regulate implantation, endometrial epithelial cells produce and secrete factors apically into the uterine cavity in the receptive phase to prepare the initial blastocyst adhesion and implantation. Organoids were recently developed from human endometrial epithelium with similar apical-basal polarity compared to endometrial gland making it an ideal model to study endometrial epithelial secretions.
Methods: Endometrial organoids were established using endometrial biopsies from women with primary infertility and normal fertility. Fertile and infertile organoids were treated with hormones to model receptive phase of the endometrial epithelium and intra-organoid fluid (IOF) was collected to compare the apical protein secretion profile and function on trophoblast cell adhesion.
Results: Our data show that infertile organoids were dysregulated in their response to estrogen and progesterone treatment. Proteomic analysis of organoid apical secretions identified 150 dysregulated proteins between fertile and infertile groups (>1.5-fold change). Trophoblast progenitor spheroids (blastocyst surrogates) treated with infertile organoid apical secretions significantly compromised their adhesion to organoid epithelial cell monolayers compared to fertile group (P < 0.0001).
Discussion: This study revealed that endometrial organoid apical secretions alter trophoblast cell adhesiveness relative to fertility status of women. It paves the way to determine the molecular mechanisms by which endometrial epithelial apical released factors regulate blastocyst initial attachment and implantation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Frontiers in endocrinology - 13(2022) vom: 01., Seite 1067648 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Wei [VerfasserIn] |
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| Links: |
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| Themen: |
Apical secretion |
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| Anmerkungen: |
Date Completed 03.01.2023 Date Revised 27.01.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fendo.2022.1067648 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM351011099 |
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| 245 | 1 | 0 | |a Infertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion |
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| 500 | |a Date Revised 27.01.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Zhou, Barton, Cui, Santos, Yang, Stern, Kieu, Teh, Ang, Lucky, Sgroi, Ye and Dimitriadis. | ||
| 520 | |a Introduction: Embryo implantation failure leads to infertility. As an important approach to regulate implantation, endometrial epithelial cells produce and secrete factors apically into the uterine cavity in the receptive phase to prepare the initial blastocyst adhesion and implantation. Organoids were recently developed from human endometrial epithelium with similar apical-basal polarity compared to endometrial gland making it an ideal model to study endometrial epithelial secretions | ||
| 520 | |a Methods: Endometrial organoids were established using endometrial biopsies from women with primary infertility and normal fertility. Fertile and infertile organoids were treated with hormones to model receptive phase of the endometrial epithelium and intra-organoid fluid (IOF) was collected to compare the apical protein secretion profile and function on trophoblast cell adhesion | ||
| 520 | |a Results: Our data show that infertile organoids were dysregulated in their response to estrogen and progesterone treatment. Proteomic analysis of organoid apical secretions identified 150 dysregulated proteins between fertile and infertile groups (>1.5-fold change). Trophoblast progenitor spheroids (blastocyst surrogates) treated with infertile organoid apical secretions significantly compromised their adhesion to organoid epithelial cell monolayers compared to fertile group (P < 0.0001) | ||
| 520 | |a Discussion: This study revealed that endometrial organoid apical secretions alter trophoblast cell adhesiveness relative to fertility status of women. It paves the way to determine the molecular mechanisms by which endometrial epithelial apical released factors regulate blastocyst initial attachment and implantation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a apical secretion | |
| 650 | 4 | |a blastocyst attachment | |
| 650 | 4 | |a endometrial organoids | |
| 650 | 4 | |a infertile organoids | |
| 650 | 4 | |a intra-organoid fluid | |
| 650 | 7 | |a Proteins |2 NLM | |
| 700 | 1 | |a Barton, Siena |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Jinwei |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, Leilani L |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Guannan |e verfasserin |4 aut | |
| 700 | 1 | |a Stern, Catharyn |e verfasserin |4 aut | |
| 700 | 1 | |a Kieu, Violet |e verfasserin |4 aut | |
| 700 | 1 | |a Teh, Wan Tinn |e verfasserin |4 aut | |
| 700 | 1 | |a Ang, Catarina |e verfasserin |4 aut | |
| 700 | 1 | |a Lucky, Tarana |e verfasserin |4 aut | |
| 700 | 1 | |a Sgroi, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Louie |e verfasserin |4 aut | |
| 700 | 1 | |a Dimitriadis, Evdokia |e verfasserin |4 aut | |
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