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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2017

Open Access 01-12-2017 | Research

Activated ovarian endothelial cells promote early follicular development and survival

Authors: Alon Kedem, Anate Aelion-Brauer, Peipei Guo, Duancheng Wen, Bi-Sen Ding, Raphael Lis, Du Cheng, Vladislav M. Sandler, Shahin Rafii, Zev Rosenwaks

Published in: Journal of Ovarian Research | Issue 1/2017

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Abstract

Background

New data suggests that endothelial cells (ECs) elaborate essential “angiocrine factors”. The aim of this study is to investigate the role of activated ovarian endothelial cells in early in-vitro follicular development.

Methods

Mouse ovarian ECs were isolated using magnetic cell sorting or by FACS and cultured in serum free media. After a constitutive activation of the Akt pathway was initiated, early follicles (50–150 um) were mechanically isolated from 8-day-old mice and co-cultured with these activated ovarian endothelial cells (AOEC) (n = 32), gel (n = 24) or within matrigel (n = 27) in serum free media for 14 days. Follicular growth, survival and function were assessed.

Results

After 6 passages, flow cytometry showed 93% of cells grown in serum-free culture were VE-cadherin positive, CD-31 positive and CD 45 negative, matching the known EC profile. Beginning on day 4 of culture, we observed significantly higher follicular and oocyte growth rates in follicles co-cultured with AOECs compared with follicles on gel or matrigel. After 14 days of culture, 73% of primary follicles and 83% of secondary follicles co-cultured with AOEC survived, whereas the majority of follicles cultured on gel or matrigel underwent atresia.

Conclusions

This is the first report of successful isolation and culture of ovarian ECs. We suggest that co-culture with activated ovarian ECs promotes early follicular development and survival. This model is a novel platform for the in vitro maturation of early follicles and for the future exploration of endothelial-follicular communication.

Capsule

In vitro development of early follicles necessitates a complex interplay of growth factors and signals required for development. Endothelial cells (ECs) may elaborate essential “angiocrine factors” involved in organ regeneration. We demonstrate that co-culture with ovarian ECs enables culture of primary and early secondary mouse ovarian follicles.
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Metadata
Title
Activated ovarian endothelial cells promote early follicular development and survival
Authors
Alon Kedem
Anate Aelion-Brauer
Peipei Guo
Duancheng Wen
Bi-Sen Ding
Raphael Lis
Du Cheng
Vladislav M. Sandler
Shahin Rafii
Zev Rosenwaks
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2017
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-017-0354-z

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