RRC ID 72015
Author Kanatsu-Shinohara M, Lee J, Miyazaki T, Morimoto H, Shinohara T.
Title Adeno-associated-virus-mediated gene delivery to ovaries restores fertility in congenital infertile mice.
Journal Cell Rep Med
Abstract Oocytes and granulosa cells closely interact with each other during follicular development, and a lack of appropriate signaling between them results in infertility. Attempts to manipulate oocyte microenvironment have been impeded by the impermeability of the blood-follicle barrier (BFB). To establish a strategy for manipulating oogenesis, we use adeno-associated viruses (AAVs), which have a unique ability of transcytosis. Microinjecting of AAVs into the ovarian stroma penetrates the BFB and achieves long-term gene expression. Introduction of an AAV carrying the mouse Kitl gene restores oogenesis in congenitally infertile KitlSl-t/KitlSl-t mutant mouse ovaries, which lack Kitl expression but contain only primordial follicles. Healthy offspring without AAV integration are born by natural mating. Therefore, AAV-mediated gene delivery not only provides a means for studying oocyte-granulosa interactions through the manipulation of the oocyte microenvironment but could also be a powerful method to treat female infertility resulting from somatic cell defects.
Volume 3(5)
Pages 100606
Published 2022-5-17
DOI 10.1016/j.xcrm.2022.100606
PII S2666-3791(22)00123-9
PMID 35584625
PMC PMC9133397
MeSH Animals Dependovirus / genetics Female Fertility / genetics Humans Infertility, Female* / genetics Mice Ovarian Follicle Ovary*
DNA material CSII-EF-MCS (RDB04378) CSII-EF-MCS-IRES2-Venus (RDB04384) pAxcw (RDB00917)