Effect of Aging on Meiosis Progression, Developmental Competence and DNA Double-Strand Breaks in Mouse Oocytes
Effect of Aging on Meiosis Progression, Developmental Competence and DNA Double-Strand Breaks in Mouse Oocytes
Lei Gao1, Gong-xue Jia2, Zheng-yuan Huang1, Ming-xing Yue3, Chao Zhang1, Shi-en Zhu1 and Xiang-wei Fu1,*
ABSTRACT
This study investigated the effect of aging on meiosis progression, embryo developmental competence and DNA double-strand breaks (DSBs) in mouse oocytes and resultant early embryos. Germinal vesicle (GV) oocytes were first cultured to monitor the progression of germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) during in vitro maturation (IVM), then the harvested metaphase II (MII) oocytes were parthenogenetically activated to evaluate pronuclear (PN) formation of parthenogenetic embryo and embryo development. The cytoplasmic maturation was examined by measuring the intracellular reactive oxygen species (ROS) and glutathione (GSH). DNA DSBs were examined by immunostaining of pi-H2AX, the marker of DNA DSBs. The results showed that the GVBD rates were similar in oocytes of young and aged mice. Polar body extrusion was significantly delayed in aged mice (P < 0.05), however the rate of polar body extrusion was similar to that of young mice at 16 h of IVM. Moreover, PN formation of parthenogenetic embryo was significantly delayed in aged mice (P < 0.05). Afterward the two groups obtained similar results with respect to the percentages of activated oocytes, 2-cell embryos and blastocysts. The cytoplasmic maturation of MII oocytes and blastocysts in aged mice were significantly compromised to those of young mice (P < 0.05). Furthermore, GV oocytes, 2-cell embryos and blastocysts showed significantly higher relative intensities of pi-H2AX in aged mice (P <0.05). Taken together, our result indicate that aging disturbed oocyte maturation and parthenogenetic embryo development, which could be related to insufficient cytoplasmic maturation and worsening DNA DSBs in oocytes and early embryos.
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August 2020
Vol. 52, Iss. 4, Pages 1225-1630
