Gene Expression Profile of Patients with Mayer-Rokitansky-Küster-Hauser Syndrome: New Insights into the Potential Role of Developmental Pathways

Abstract

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis. A group of eight out of sixteen MRKHS patients that underwent reconstruction of neovagina with an autologous in vitro cultured vaginal tissue were subjected to microarray analysis and compared with five healthy controls. Results obtained by array were confirmed by qRT-PCR and further extended to other eight MRKHS patients. Gene profiling of MRKHS patients delineated 275 differentially expressed genes, of which 133 downregulated and 142 upregulated. We selected six deregulated genes (MUC1, HOXC8, HOXB2, HOXB5, JAG1 and DLL1) on the basis of their fold change, their differential expression in most patients and their relevant role in embryological development. All patients showed upregulation of MUC1, while HOXB2 and HOXB5 were downregulated, as well as Notch ligands JAG1 and DLL1 in the majority of them. Interestingly, HOXC8 was significantly upregulated in 47% of patients, with a differential expression only in MRKHS type I patients. Taken together, our results highlighted the dysregulation of developmental genes, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract and providing a useful clue for understanding the pathophysiology of MRKHS.

Recent advances in the molecular mechanisms of Mayer-Rokitansky-Küster-Hauser syndrome

“…Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a disease caused by congenital absence of the uterus and two-thirds of the upper vagina (1). Women with MRKHS develop normal secondary sexual characteristics and have a female chromosome pattern (46,XX) (1).…”

“…Women with MRKHS develop normal secondary sexual characteristics and have a female chromosome pattern (46,XX) (1). MRKHS occurs in one in 4,500 women globally (1) and is the second leading cause of primary amenorrhea (2).…”

Evaluation of vaginal agenesis treated with the modified McIndoe technique: A retrospective study

“…Several modifications of this technique, especially regarding the material adopted for the canal lining, have been proposed. These include the use of the peritoneum, amnion, allogenic epidermal sheets, Interceed absorbable adhesion barrier, and autologous buccal mucosa (11,12). Moreover, in vitro autologous vaginal cell cultures obtained from biopsies from the vaginal vestibule were used for the epithelization of the neovaginal walls by Panici for the first time in 2007.…”

Genetic aspects of vagina and the uterus aplasia: the history

“…Таким образом, как полагают иссле-дователи, изменение экспрессии или наличие де-фекта в одном или нескольких генах HOX может объ-яснить развитие аплазии влагалища и матки. Обна-ружение мутации в пределах промотора гена HOXA13 [45] укрепляет эту гипотезу, но требует дополнитель-ных исследований [46,47].…”