Abnormal zona pellucida and follicular development in ZP1-mutant macaquesOACSCDCSTPCD
Zona pellucida glycoprotein-1(ZP1)is essential for maintaining oocyte structural integrity and facilitating fertilization.Mutations in ZP1 are strongly associated with primary infertility disorders such as fertilization failure and empty follicle syndrome;however,the absence of accurate experimental models has hindered mechanistic understanding and obscured the etiological basis of ZP1-related infertility.In this study,CRISPR/Cas9-mediated genome editing was employed to generate two ZP1-edited cynomolgus macaques(Macaca fascicularis),designated#ZP1-1(male)and#ZP1-2(female).Following sexual maturation,oocytes retrieved from#ZP1-2 through superovulation exhibited a marked increase in zona pellucida-deficient oocytes and a significant reduction in maturation rates compared to controls.Integrated analyses,including immunofluorescence staining,transmission electron microscopy,transcriptomic profiling of oocytes,and histopathological examination of ovarian tissue,revealed disrupted folliculogenesis and oocyte anomalies consistent with phenotypes observed in human empty follicle syndrome.These findings establish the ZP1-knockout cynomolgus macaque as the first non-human primate model of ZP1-related infertility,providing a valuable platform for elucidating disease mechanisms and informing the development of targeted interventions for infertility arising from ZP gene mutations.
Wei Meng;Bao-Zhen Liu;Dan Huang;Yu-Tao Fan;Cheng-Gang Xiong;Ying-Ting Zhang;Lei-Lei Zhao;Yong-Long Guo;Mu-Hua Lai;Xin-Yuan Zhao;Ya-Qing Li;Shi-Kun Zhao;Jing-Tao Zeng;Chuan-He Liu;Ji-Long Liu;Chen-Hui Ding;Shi-Hua Yang
College of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaKey Laboratory of Reproductive Medicine of Guangdong Province,School of Life Sciences and First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510275,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaKey Laboratory of Reproductive Medicine of Guangdong Province,School of Life Sciences and First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510275,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaInstrumental Analysis&Research Center,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,ChinaKey Laboratory of Reproductive Medicine of Guangdong Province,School of Life Sciences and First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510275,ChinaCollege of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong 510642,China
医药卫生
ZP1Zona pellucidaCynomolgus macaquesInfertility
《Zoological Research》 2025 (5)
P.1093-1107,15
supported by the National Key R&D Program of China(2018YFA0801404,2023YFC3403400)National Natural Science Foundation of China(81941006)Guangdong Special Support Program(2019BT02Y276)Specific University Discipline Construction Project(2023B10564003)Guangdong Natural Science Funds for Distinguished Young Scholars(2021B1515020079)。
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