title: Survivin is essential for fertile egg production and female fertility in mice.
abstract: Survivin is the smallest member of the inhibitor of apoptosis protein (IAP) family and acts as a bifunctional protein involved in mitosis regulation and apoptosis inhibition. To identify the physiological role of Survivin in female reproduction, we selectively disrupted Survivin expression in oocytes and granulosa cells (GCs), two major cell types in the ovary, by two different Cre-Loxp conditional knockout systems, and found that both led to defective female fertility. Survivin deletion in oocytes did not affect oocyte growth, viability and ovulation, but caused tetraploid egg production and thus female infertility. Further exploration revealed that Survivin was essential for regulating proper meiotic spindle organization, spindle assembly checkpoint activity, timely metaphase-to-anaphase transition and cytokinesis. Mutant mice with Survivin depleted in GCs showed reduced ovulation and subfertility, caused by defective follicular growth, increased follicular atresia and impaired luteinization. These findings suggest that Survivin has an important role in regulating folliculogenesis and oogenesis in the adult mouse ovary.
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Jiang
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: M-W
authors.initials: MW
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Z-B
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: F
authors.initials: F
authors.lastname: Lin
authors.affiliation: 1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: S-T
authors.initials: ST
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Ouyang
authors.affiliation: Life Science Institute, Zhejiang University, Hangzhou 310000, China.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Fan
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
authors.forename: H
authors.initials: H
authors.lastname: Schatten
authors.affiliation: 1] Advanced Medical Discovery Institute, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada M5G 2C1 [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1 [3] Department of Immunology, University of Toronto, Toronto, Ontario, Canada M5G 2C1.
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Q-Y
authors.initials: QY
authors.lastname: Sun
mesh_terms: D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D033481:Chromosomes, Mammalian / Q000378:metabolism; D048749:Cytokinesis; D015536:Down-Regulation; D005260:Female; D005298:Fertility; D017353:Gene Deletion; D006107:Granulosa Cells / Q000378:metabolism; D055429:Growth Differentiation Factor 9 / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D034461:Luteinization; D059566:M Phase Cell Cycle Checkpoints; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D009866:Oogenesis; D010060:Ovulation; D012097:Repressor Proteins / Q000378:metabolism*; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D064173:Anaphase-Promoting Complex-Cyclosome; C045073:Cre recombinase; D019426:Integrases