Activated ovarian endothelial cells promote early follicular development and survival

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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Article number1064
JournalJournal of Ovarian Research
Volume10
Issue number1
DOIs
StatePublished - 19 Sep 2017
Externally publishedYes

Keywords

  • Endothelial cells
  • Follicle culture
  • Follicular activation
  • in-vitro maturation

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