TRANSLATIONAL IMPACT
Clinical issue

Oculodentodigital dysplasia (ODDD) is a rare genetic abnormality that affects multiple organs, most obviously the eyes (microophthalmia), teeth (enamel hypoplasia) and digits (oligosyndactyly of the fingers and toes). In some affected individuals, variable neurological problems and heart and skin defects have also been described. The diverse features that characterize this inherited syndrome reflect the widespread expression of its affected gene, GJA1, which encodes connexin43 (Cx43). Connexins form the intercellular membrane channels of gap junctions – structures that allow cells to pass ions and small molecules between them to coordinate their functions. Studies in knockout mice indicate that connexins, including Cx43, play essential developmental and physiological roles.

Results

Cx43 is necessary for mouse oogenesis and is widely expressed in human ovaries. The role for Cx43 in reproduction is not well understood in mice and has not been studied in humans. This study examines Cx43 and its influence on reproductive health using mice carrying a Cx43 mutation that causes a phenotype similar to ODDD in humans. Their results show that mutant mice are subfertile; they have smaller litters and their follicles do not respond properly to hormone stimulation.

Implications and future directions

Connexins play an important role in the female reproductive system and the research presented here demonstrates that Cx43 contributes to the normal process of oogenesis and fertility. This study encourages a closer examination of the reproductive history of ODDD women as it may reveal previously undiagnosed problems. Furthermore, using this mouse model to study the role of Cx43 in oogenesis might lead to new treatments for human reproductive problems, including infertility.