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Publication : Oocyte-specific deletion of G<sub>s</sub>α induces oxidative stress and deteriorates oocyte quality in mice.

First Author  Xie Y Year  2018
Journal  Exp Cell Res Volume  370
Issue  2 Pages  579-590
PubMed ID  30026030 Mgi Jnum  J:268506
Mgi Id  MGI:6271254 Doi  10.1016/j.yexcr.2018.07.023
Citation  Xie Y, et al. (2018) Oocyte-specific deletion of Gsalpha induces oxidative stress and deteriorates oocyte quality in mice. Exp Cell Res 370(2):579-590
abstractText  The stimulatory heterotrimeric Gs protein alpha subunit (Gsalpha) is a ubiquitous guanine nucleotide-binding protein that regulates the intracellular cAMP signaling pathway and consequently participates in a wide range of biological events. In the reproductive system, despite Gsalpha being associated with oocyte meiotic arrest in vitro, the exact role of Gsalpha in female fertility in vivo remains largely unknown. Here, we generated oocyte-specific Gsalpha knockout mice by using the Cre/LoxP system. We observed that the deletion of Gsalpha caused complete female infertility. Exclusion of post-implantation abnormalities, oogenesis, fertilization, and early embryo development was subsequently monitored; meiosis in Gsalpha-deficient oocytes precociously resumed in only 43% of antral follicles from mutant mice, indicating that alteration of meiotic pause was not the key factor in infertility. Ovulation process and number were normal, but the rate of morphological abnormal oocytes was apparently increased; spindle organization, fertilization, and early embryo development were impaired. Furthermore, the level of ROS (reactive oxygen species) and the mitochondrial aggregation increased, and antioxidant glutathione (GSH) content, ATP level, mtDNA copy number, and mitochondrial membrane potential decreased in Gsalpha-deficient oocytes. GV oocytes from mutant mice showed early-stage apoptosis. Meanwhile, the Gsalpha knockout-induced decline in oocyte quality and low developmental potential was partially rescued by antioxidant supplementation. To sum up, our results are the first to reveal that the profile of Gsalpha oocyte-specific deletion caused female infertility in vivo, and oxidative stress plays an important role in this event.
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