Female infertility in mice lacking connexin 37.
The signals regulating ovarian follicle development and the mechanisms by which they are communicated are largely undefined. At birth, the ovary contains primordial follicles consisting of meiotically arrested oocytes surrounded by a single layer of supporting (granulosa) cells. Periodically, subsets of primordial follicles undergo further development during which the oocyte increases in size and the granulosa cells proliferate, stratify and develop a fluid-filled antrum. After ovulation, oocytes resume meiosis and granulosa cells retained in the follicle differentiate into steroidogenic cells, forming the corpus luteum. It has been proposed that intercellular signalling through gap junction channels may influence aspects of follicular development. Gap junctions are aggregations of intercellular channels composed of connexins, a family of at least 13 related proteins that directly connect adjacent cells allowing the diffusional movement of ions, metabolites, and other potential signalling molecules. Here we show that connexin 37 is present in gap junctions between oocyte and granulosa cells and that connexin 37-deficient mice lack mature (Graafian) follicles, fail to ovulate and develop numerous inappropriate corpora lutea. In addition, oocyte development arrests before meiotic competence is achieved. Thus, cell-cell signalling through intercellular channels critically regulates the highly coordinated set of cellular interactions required for successful oogenesis and ovulation.
Simon
A M
AM
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Goodenough
D A
DA
Li
E
E
Paul
D L
DL
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D017630:Connexins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D003338:Corpus Luteum / Q000648:ultrastructure; D005260:Female; D017629:Gap Junctions / Q000502:physiology; D018390:Gene Targeting; D006107:Granulosa Cells / Q000502:physiology; D007247:Infertility, Female / Q000209:etiology* / Q000235:genetics; D008297:Male; D008540:Meiosis; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D009866:Oogenesis / Q000502:physiology; D006080:Ovarian Follicle / Q000502:physiology* / Q000648:ultrastructure; D010053:Ovary / Q000502:physiology / Q000648:ultrastructure; D010060:Ovulation / Q000502:physiology; D000097006:Gap Junction alpha-4 Protein
D017630:Connexins; D000097006:Gap Junction alpha-4 Protein