Oocyte-directed depletion of connexin43 using the Cre-LoxP system leads to subfertility in female mice

Gap junctions, predominately comprising connexin43 (Cx43), mediate cell-to-cell communication within the ovarian follicle. However, the partaking of Cx43 in the formation of the gap junction channels, between the oocyte and the somatic cells, is controversial. We addressed this dispute by crossing females that carry a Cx43 coding region, flanked by loxP recognition sites, with males expressing the Cre recombinase under the control of Zp3 promoter. Oocytes of the resultant Zp3Cre;Gja1lox/lox mice did not express Cx43 and were referred to as Cx43del/del. Unexpectedly, a decrease in Cx43 was observed in cumulus/granulosa cells of some follicles as well. Nevertheless, no histological abnormalities were detected in the ovaries of the Zp3Cre;Gja1lox/lox mice. Furthermore, these mice ovulated normally and developed fully functional corpora lutea. Additionally, the ovarian Cx43del/del oocytes were meiotically arrested and transferred Lucifer yellow to the surrounding cumulus cells. However, mating Zp3Cre;Gja1lox/lox females with wild-type males resulted in a reduced rate of parturition and a substantial decrease in litter size. Further examination revealed that although preimplantation development of Zp3Cre;Gja1lox/+ embryos was normal, the blactocysts exhibited impaired implantation. Our data suggest that total ablation of Cx43 in the oocyte, combined with its decrease in the surrounding somatic cells, allows normal oogenesis and folliculogenesis, ovulation and early embryonic development but severely impairs the implantation capacity of the resulting blactocysts.