Ex vivo reconstitution of fetal oocyte development in humans and cynomolgus monkeys

• DOI: 10.15252/embj.2022110815
• Publication Date: 2022-08-01T10:00:05Z
• 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
• Keywords: 0301 basic medicine; Ovary; fetal oocytes; Macaca fascicularis; Meiosis; Mice; 03 medical and health sciences; ex vivo culture; Oogenesis; monkeys; Oocytes; Animals; Humans; Female; humans; meiotic prophase

AbstractIn 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.