Adeno-associated-virus-mediated gene delivery to ovaries restores fertility in congenital infertile mice

Cell Rep Med. 2022 May 17;3(5):100606. doi: 10.1016/j.xcrm.2022.100606. Epub 2022 Apr 27.


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.

Keywords: Kitl; adeno-associated virus; infertility; oogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dependovirus / genetics
  • Female
  • Fertility / genetics
  • Humans
  • Infertility, Female* / genetics
  • Mice
  • Ovarian Follicle
  • Ovary*