O-207 zp1 mutation affects oocyte energy metabolism and leads to oocyte apoptosis

Abstract Study question How does the zp1 variation leads to apoptosis oocytes in antral follicular and infertility females? Summary answer Mutant induces abnormal pyruvate transport leading accumulation of reactive oxygen species (ROS), which activates mitochondria-mediated pathway apoptosis. What is known already Previous research reported a mutation human infertility, we develop homologous rat strain investigate pathogenic effect. The ovaries homozygous posses growing fully grown oocytes, completely lack zona pellucida. Only 1-2 eggs were recovered from oviducts per superovulated rat, not surrounded by pellucida thus lost their fertilization capacity vitro.Further studies showed that female rats only lacked ZP but also TZPs (an important communication bridge between granulosa cells oocytes), caval follicles obvious apoptotic signals. design, size, duration In this study, 10 Sprague-Dawley used at 8 weeks age (5 wild-type 5 mutant respectively). Participants/materials, setting, methods We CRISPR/Cas 9-mediated genomic editing technology model carrying 8bp deleted Zp1 gene(Zp1mt/mt). sacrificed cervical vertebra dislocation isolated immediately. Then using bulk RNA sequencing Zp1mt/mt identify differential expression gene two groups.The differentially expressed genes enriched KEGG verified qRT-PCR vitro functional experiments. Main results role chance Total 293 DEGs obtained, 144 up-regulated 149 down-regulated. biological process mainly involved redox reaction negative regulation cell migration.Down-regulated are growth development,and related oocyte energy metabolism. order verify DEG obtained sequencing, Gcgr, Plcβ2, Aox3 Hpgd metabolism qRT-PCR. consistent with trend data.The there was no significant difference Pkm cells, while Pdk4 oocytes. For ROS detection, 52 4 48 6 wide-type analyzed for species. IOD significantly higher than wild-type,indicating content increased, statistically significant.The detection protein shows probability ofwild-type. Limitations, reasons caution This study provides more experimental basis data support involvement oogenesis, effect deficiency on dynamic transcriptional developing oocytes-granulosa specific molecular mechanism remain be further explored. Wider implications findings work key insights into crucial features animal ovaries, offers clues exploring potential development due deficiency. Trial registration number none