Gershon Eran, Plaks Vicki, Aharon Idan, Galiani Dalia, Reizel Yitzhak, Sela-Abramovich Sagit, Granot Irit, Winterhager Elke, Dekel Nava
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Dev Biol. 2008 Jan 1;313(1):1-12. doi: 10.1016/j.ydbio.2007.08.041. Epub 2007 Aug 31.
Gap junctions, predominantly 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;Gja1(lox/lox) mice did not express Cx43 and were referred to as Cx43(del/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;Gja1(lox/lox) mice. Furthermore, these mice ovulated normally and developed fully functional corpora lutea. Additionally, the ovarian Cx43(del/del) oocytes were meiotically arrested and transferred Lucifer yellow to the surrounding cumulus cells. However, mating Zp3Cre;Gja1(lox/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;Gja1(lox/+) 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.
缝隙连接主要由连接蛋白43(Cx43)组成,介导卵泡内的细胞间通讯。然而,Cx43在卵母细胞与体细胞之间缝隙连接通道形成中的参与情况存在争议。我们通过将携带loxP识别位点侧翼的Cx43编码区的雌性与在Zp3启动子控制下表达Cre重组酶的雄性杂交来解决这一争议。所得Zp3Cre;Gja1(lox/lox)小鼠的卵母细胞不表达Cx43,被称为Cx43(del/del)。出乎意料的是,在一些卵泡的卵丘/颗粒细胞中也观察到Cx43减少。然而,在Zp3Cre;Gja1(lox/lox)小鼠的卵巢中未检测到组织学异常。此外,这些小鼠排卵正常并发育出功能完全正常的黄体。另外,卵巢Cx43(del/del)卵母细胞减数分裂停滞,并将荧光黄转移至周围的卵丘细胞。然而,将Zp3Cre;Gja1(lox/lox)雌性与野生型雄性交配导致分娩率降低和窝仔数大幅减少。进一步检查发现,虽然Zp3Cre;Gja1(lox/+)胚胎的植入前发育正常,但囊胚的着床受损。我们的数据表明,卵母细胞中Cx43的完全缺失,连同其周围体细胞中Cx43的减少,允许正常的卵子发生、卵泡发生、排卵和早期胚胎发育,但严重损害了所得囊胚的着床能力。