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Homeobox protein Hox-A11 (Homeobox protein Hox-1I) [HOX1I]


[Connective tissue and prolapse genesis].

The pathophysiology of pelvic floor disorders still remains not well understood. Increasing age as well as vaginal multiparity are the main commonly accepted factors. The hypothesis of a defect of connective tissues of the pelvic floor with aging due to collagen deficiency and/or elastic fiber degradation is often highlighted. The issue of a potential protective role of HRT is also discussed although the recent results from the WHI would suggest a negative impact of HRT on urinary incontinence, especially when HRT is initiated in elderly women, far from the menopause. Nevertheless, environmental factors cannot explain the full pathogenesis of pelvic organ prolapse (POP) and the contribution of genetic factors to the development of pelvic floor disorders is widely recognized. Support for a genetic influence on POP derives from reports suggesting that heritability is a strong contributing factor and a familial history of POP is considered as a classical risk factor. However, the characterization of the underlying molecular mechanisms remains limited, since POP may be considered the end result of a multifactorial process leading to destruction of vaginal wall connective tissue. Experimental studies in mice with null mutations in the genes encoding different putative factors involved in elastic fibers remodeling and homeostasis are crucial in the understanding of the pathogenesis of POP. Mice with null mutation in the gene encoding lysyl oxidase-like 1 (LOXL1) or fibulin-5, demonstrate signs of elastinopathy including the development of a POP in the postpartum. Likewise, homeobox genes such as HOXA11, which are essential in the embryonic development of the urogenital tract might also be involved in the pathogenesis of POP. The better understanding of the underlying determinants of pelvic floor disorders with a special focus on genetic factors may offer new therapeutic strategies, in addition to or replacement of surgical procedures.

MeSH Terms

  • Aging
  • Amino Acid Oxidoreductases
  • Animals
  • Collagen
  • Connective Tissue
  • Elastic Tissue
  • Estrogen Replacement Therapy
  • Extracellular Matrix Proteins
  • Female
  • Homeodomain Proteins
  • Humans
  • Mice
  • Mutation
  • Pelvic Floor
  • Pelvic Organ Prolapse
  • Recombinant Proteins
  • Urinary Incontinence