title: Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice.
abstract: Increases in the aneuploidy rate caused by the deterioration of cohesion with increasing maternal age have been well documented. However, the molecular mechanism for the loss of cohesion in aged oocytes remains unknown. In this study, we found that intracellular pH (pHi) was elevated in aged oocytes, which might disturb the structure of the cohesin ring to induce aneuploidy. We observed for the first time that full-grown germinal vesicle (GV) oocytes displayed an increase in pHi with advancing age in CD1 mice. Furthermore, during the in vitro oocyte maturation process, the pHi was maintained at a high level, up to ∼7.6, in 12-month-old mice. Normal pHi is necessary to maintain protein localization and function. Thus, we put forward a hypothesis that the elevated oocyte pHi might be related to the loss of cohesion and the increased aneuploidy in aged mice. Through the in vitro alkalinization treatment of young oocytes, we observed that the increased pHi caused an increase in the aneuploidy rate and the sister inter-kinetochore (iKT) distance associated with the strength of cohesion and caused a decline in the cohesin subunit SMC3 protein level. Young oocytes with elevated pHi exhibited substantially the increase in chromosome misalignment.
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Cheng
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Tang
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Su-Ren
authors.initials: SR
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Shou-Long
authors.initials: SL
authors.lastname: Deng
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Xiu-Xia
authors.initials: XX
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Chen-Xi
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Yi-Xun
authors.initials: YX
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000502:physiology; D000468:Alkalies / Q000494:pharmacology; D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016922:Cellular Senescence; D027963:Chloride-Bicarbonate Antiporters; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D033481:Chromosomes, Mammalian / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D000468:Alkalies; D018797:Cell Cycle Proteins; D027963:Chloride-Bicarbonate Antiporters; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins; C492317:SMC3 protein, mouse
keywords: aging; alkalinization; chromosome aneuploidy; cohesion; oocytes; pHi