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Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):9021-6. doi: 10.1073/pnas.1603817113. Epub 2016 Jul 25.

Complete in vitro generation of fertile oocytes from mouse primordial germ cells.

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Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan;
NODAI Genome Research Center, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan;
Department of Developmental Stem Cell Biology, Faculty of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Higashi-ku, Fukuoka 812-8582, Japan;
Division of Animal Breeding and Reproduction Research, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki 305-0901, Japan
Department of Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo 156-8502, Japan;


Reconstituting gametogenesis in vitro is a key goal for reproductive biology and regenerative medicine. Successful in vitro reconstitution of primordial germ cells and spermatogenesis has recently had a significant effect in the field. However, recapitulation of oogenesis in vitro remains unachieved. Here we demonstrate the first reconstitution, to our knowledge, of the entire process of mammalian oogenesis in vitro from primordial germ cells, using an estrogen-receptor antagonist that promotes normal follicle formation, which in turn is crucial for supporting oocyte growth. The fundamental events in oogenesis (i.e., meiosis, oocyte growth, and genomic imprinting) were reproduced in the culture system. The most rigorous evidence of the recapitulation of oogenesis was the birth of fertile offspring, with a maximum of seven pups obtained from a cultured gonad. Moreover, cryopreserved gonads yielded functional oocytes and offspring in this culture system. Thus, our in vitro system will enable both innovative approaches for a deeper understanding of oogenesis and a new avenue to create and preserve female germ cells.


follicle formation; in vitro; oocytes; oogenesis; primordial germ cells

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