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*
|
Resource |
DNA material |
CSII-EF-MCS (RDB04378)
CSII-EF-MCS-IRES2-Venus (RDB04384)
pAxcw (RDB00917) |