Ex Vivo Reconstitution of Fetal Oocyte Development in Humans and Cynomolgus Monkeys

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2022 Aug 1

PMID 35912849

Authors

Ken Mizuta

Yoshitaka Katou

Baku Nakakita

Aoi Kishine

Yoshiaki Nosaka

Saki Saito

Chizuru Iwatani

Hideaki Tsuchiya

Ikuo Kawamoto

Masataka Nakaya

Tomoyuki Tsukiyama

Masahiro Nagano

Yoji Kojima

Tomonori Nakamura

Yukihiro Yabuta

Akihito Horie

Masaki Mandai

Hiroshi Ohta

Mitinori Saitou

Affiliations

Soon will be listed here.

Abstract

In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates.

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