title: Scaffold subunit Aalpha of PP2A is essential for female meiosis and fertility in mice.
abstract: Ppp2r1a encodes the scaffold subunit Aalpha of protein phosphatase 2A (PP2A), which is an important and ubiquitously expressed serine threonine phosphatase family and plays a critical role in many fundamental cellular processes. To identify the physiological role of PP2A in female germ cell meiosis, we selectively disrupted Ppp2r1a expression in oocytes by using the Cre-Loxp conditional knockout system. Here we report for the first time that oocyte-specific deletion of Ppp2r1a led to severe female subfertility without affecting follicle survival, growth, and ovulation. PP2A-Aalpha was essential for regulating oocyte meiotic maturation because depletion of PP2A-Aalpha facilitated germinal vesicle breakdown, causing elongation of the MII spindle and precocious separation of sister chromatids. The resulting eggs had high risk of aneuploidy, though they could be fertilized, leading to defective embryonic development and thus subfertility. Our findings provide strong evidence that PP2A-Aalpha within the oocyte plays an indispensable role in oocyte meiotic maturation, though it is dispensable for folliculogenesis in the mouse ovary.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Meng-Wen
authors.initials: MW
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zong-Zhe
authors.initials: ZZ
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shu-Tao
authors.initials: ST
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Liang
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri.
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China sunqy@ioz.ac.cn.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D000818:Animals; D005260:Female; D005298:Fertility / Q000502:physiology*; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism*; D009866:Oogenesis / Q000502:physiology; D010060:Ovulation / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D054648:Protein Phosphatase 2
keywords: PP2A; PSSC; conditional knockout; meiosis; oocyte