{"title":"腺病毒介导的基因传递恢复先天性不育雌性小鼠的生育能力。","authors":"Mito Kanatsu-Shinohara, Jiyoung Lee, Takehiro Miyazaki, Hiroko Morimoto, Takashi Shinohara","doi":"10.1262/jrd.2022-090","DOIUrl":null,"url":null,"abstract":"<p><p>Oogenesis depends on close interactions between oocytes and granulosa cells. Abnormal signaling between these cell types can result in infertility. However, attempts to manipulate oocyte-granulosa cell interactions have had limited success, likely due to the blood-follicle barrier (BFB), which prevents the penetration of exogenous materials into ovarian follicles. Here, we used adenoviruses (AVs) to manipulate the oocyte-granulosa cell interactions. AVs penetrated the BFB and transduced granulosa cells through ovarian microinjection. Although AVs caused transient inflammation, they did not impair fertility in wild-type mice. Introduction of Kitl-expressing AVs into congenitally infertile Kitl<sup>Sl-t</sup>/Kitl<sup>Sl-t</sup> mutant mouse ovaries, which contained only primordial follicles because of a lack of Kitl expression, restored fertility through natural mating. The offspring showed no evidence of AV integration and exhibited normal genomic imprinting patterns for imprinted genes. These results demonstrate the usefulness of AVs for manipulating oogenesis and suggest the possibility of gene therapies for human female infertility.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2022-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/e1/jrd-68-369.PMC9792657.pdf","citationCount":"0","resultStr":"{\"title\":\"Adenovirus-mediated gene delivery restores fertility in congenitally infertile female mice.\",\"authors\":\"Mito Kanatsu-Shinohara, Jiyoung Lee, Takehiro Miyazaki, Hiroko Morimoto, Takashi Shinohara\",\"doi\":\"10.1262/jrd.2022-090\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Oogenesis depends on close interactions between oocytes and granulosa cells. Abnormal signaling between these cell types can result in infertility. However, attempts to manipulate oocyte-granulosa cell interactions have had limited success, likely due to the blood-follicle barrier (BFB), which prevents the penetration of exogenous materials into ovarian follicles. Here, we used adenoviruses (AVs) to manipulate the oocyte-granulosa cell interactions. AVs penetrated the BFB and transduced granulosa cells through ovarian microinjection. Although AVs caused transient inflammation, they did not impair fertility in wild-type mice. Introduction of Kitl-expressing AVs into congenitally infertile Kitl<sup>Sl-t</sup>/Kitl<sup>Sl-t</sup> mutant mouse ovaries, which contained only primordial follicles because of a lack of Kitl expression, restored fertility through natural mating. The offspring showed no evidence of AV integration and exhibited normal genomic imprinting patterns for imprinted genes. These results demonstrate the usefulness of AVs for manipulating oogenesis and suggest the possibility of gene therapies for human female infertility.</p>\",\"PeriodicalId\":16942,\"journal\":{\"name\":\"Journal of Reproduction and Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2022-12-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/e1/jrd-68-369.PMC9792657.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Reproduction and Development\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1262/jrd.2022-090\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"AGRICULTURE, DAIRY & ANIMAL SCIENCE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Reproduction and Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1262/jrd.2022-090","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"AGRICULTURE, DAIRY & ANIMAL SCIENCE","Score":null,"Total":0}
Adenovirus-mediated gene delivery restores fertility in congenitally infertile female mice.
Oogenesis depends on close interactions between oocytes and granulosa cells. Abnormal signaling between these cell types can result in infertility. However, attempts to manipulate oocyte-granulosa cell interactions have had limited success, likely due to the blood-follicle barrier (BFB), which prevents the penetration of exogenous materials into ovarian follicles. Here, we used adenoviruses (AVs) to manipulate the oocyte-granulosa cell interactions. AVs penetrated the BFB and transduced granulosa cells through ovarian microinjection. Although AVs caused transient inflammation, they did not impair fertility in wild-type mice. Introduction of Kitl-expressing AVs into congenitally infertile KitlSl-t/KitlSl-t mutant mouse ovaries, which contained only primordial follicles because of a lack of Kitl expression, restored fertility through natural mating. The offspring showed no evidence of AV integration and exhibited normal genomic imprinting patterns for imprinted genes. These results demonstrate the usefulness of AVs for manipulating oogenesis and suggest the possibility of gene therapies for human female infertility.
期刊介绍:
Journal of Reproduction and Development (JRD) is the
official journal of the Society for Reproduction and Development,
published bimonthly, and welcomes original articles. JRD
provides free full-text access of all the published articles on
the web. The functions of the journal are managed by Editorial
Board Members, such as the Editor-in-Chief, Co-Editor-inChief, Managing Editors and Editors. All manuscripts are
peer-reviewed critically by two or more reviewers. Acceptance
is based on scientific content and presentation of the materials.
The Editors select reviewers and correspond with authors. Final
decisions about acceptance or rejection of manuscripts are made
by the Editor-in-Chief and Co-Editor-in-Chief.