Pathogenesis and aetiology of female genital malformations

Abstract

Aims: To describe the defects of normal embryological development that lie beneath female genital malformations and to review the available data on the possible aetiology of these defects.Brief description of the reviewed data: Female genital malformations are the result of failures in the proper development, canalization, fusion of and re-absorption of the midline septum of the Mãllerian ducts. The aetiologies for these anomalies remain mostly unknown. The role of a number of genes has been reviewed, but research has failed to establish an aetiological relationship with a particular mutation. Such malformations appear to be mainly caused by alterations in the expression of developmental genes as a result of exposure to exogenous factors during embryogenesis, like endocrine disruptors.Clinical implications: The lack of findings does not support mutation screening for women with genital malformations. A clinical investigation is important to exclude the presence of an underlying genetic syndrome. A thorough investigation of the anatomy of the reproductive tract is also recommended when prenatal exposure to endocrine disruptors is suspected.Open issues for further research: Future research should aim in elucidating how genes orchestrate a highly organized developmental process. Further investigation is also required to identify additional exogenous estrogenic factors, which alter the expression pattern of fundamental developmental genes.