title: Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro.
abstract: In vitro generation of functional gametes is a promising approach for treating infertility, although faithful replication of meiosis has proven to be a substantial obstacle to deriving haploid gamete cells in culture. Here we report complete in vitro meiosis from embryonic stem cell (ESC)-derived primordial germ cells (PGCLCs). Co-culture of PGCLCs with neonatal testicular somatic cells and sequential exposure to morphogens and sex hormones reproduced key hallmarks of meiosis, including erasure of genetic imprinting, chromosomal synapsis and recombination, and correct nuclear DNA and chromosomal content in the resulting haploid cells. Intracytoplasmic injection of the resulting spermatid-like cells into oocytes produced viable and fertile offspring, showing that this robust stepwise approach can functionally recapitulate male gametogenesis in vitro. These findings provide a platform for investigating meiotic mechanisms and the potential generation of human haploid spermatids in vitro.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; College of the Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xuepeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; College of Life Science, Anhui University of China, Hefei 230601, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Histology and Embryology, Medical College of Yangzhou University, Yangzhou 225001, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guihai
authors.initials: G
authors.lastname: Feng
authors.affiliation: Molecular and Cell Genetics Laboratory, Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zhaoxiaoyang@smu.edu.cn.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. Electronic address: shajh@njmu.edu.cn.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: qzhou@ioz.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D018920:Coculture Techniques; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D013087:Spermatids / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis