Jin Sun
Yanping Jia
Jiqing Yin
Yalin Zhang
Yanhe Li
Rui Gao
Xiling Du
Kunming Li
Jiaming Lin
Zhifen Tu
Yu Wang
Jiaping Pan
Shanshan Liang
Yi Guo
Jingling Ruan
Xiaochen Kou
Yanhong Zhao
Hong Wang
Cizhong Jiang
Fengchao Wang
Xiaoming Teng
Wenqiang Liu
Shaorong Gao
aClinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
bNational Institute of Biological Sciences, NIBS, Beijing, 102206, China
More InformationCorresponding author: E-mail address: tengxiaoming@51mch.com (Xiaoming Teng);E-mail address: liuwenqiang@tongji.edu.cn (Wenqiang Liu);E-mail address: gaoshaorong@tongji.edu.cn (Shaorong Gao)
Publish Date:2020-06-25
Abstract
Abstract
Poor oocyte quality is associated with early embryo developmental arrest and infertility. Maternal gene plays crucial roles in the regulation of oocyte maturation, and its mutation is a common cause of female infertility. However, how to improve oocyte quality and develop effective therapy for maternal gene mutation remains elusive. Here, we use Zar1 as an example to assess the feasibility of genome transfer to cure maternal gene mutation–caused female infertility. We first discover that cytoplasmic deficiency primarily leads to Zar1-null embryo developmental arrest by disturbing maternal transcript degradation and minor zygotic genome activation (ZGA) during the maternal-zygotic transition. We next perform genome transfer at the oocyte (spindle transfer or polar body transfer) and zygote (early pronuclear transfer or late pronuclear transfer) stages to validate the feasibility of preventing Zar1 mutation–caused infertility. We finally demonstrate that genome transfer either at the oocyte or at the early pronuclear stage can support normal preimplantation embryo development and produce live offspring. Moreover, those pups grow to adulthood and show normal fertility. Therefore, our findings provide an effective basis of therapies for the treatment of female infertility caused by maternal gene mutation.Keywords: Infertility,
Oocytes,
Maternal-zygotic transition,
ZGA,
Spindle transfer,
Genome transfer
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