Vaginal Agenesis, the Hymen, and Associated Anomalies

Kimberley, Natalie; Hutson, John M.; Southwell, Bridget R.; Grover, Sonia

doi:10.1016/j.jpag.2011.08.003

Cited by 57 publications

(29 citation statements)

References 28 publications

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“…In humans, mutations in the JAG1 gene cause the Alagille syndrome, characterized by severe cardiac malformation and developmental anomalies in several organs, including kidney [27], [28]. Perturbations in Notch signalling also contribute to the aetiology of Klippel-Feil syndrome [29] and spondylocostal dysostosis [30], skeletal disorders often observed in association with vaginal agenesis [31], [32]. Such data led us to hypothesize a role for this gene family in the aetiopathogenesis of type II MRKHS.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…Other congenital anomalies commonly associated with MDAs include those of the vertebral bodies (29%), such as wedged or fused vertebral bodies and spina bifida (22%-23%), cardiac anomalies (14.5%), and syndromes such as Klippel-Feil syndrome (7%) (6,7). Buttram and Gibbons (8) proposed an MDA classification in 1979, which was subsequently modified by the American Society for Reproductive Medicine in 1988 (formerly the American Fertility Society) (9).…”

Section: Introductionmentioning

confidence: 99%

Imaging of Müllerian Duct Anomalies

Behr¹,

Courtier²,

Qayyum³

2012

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202

175

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The müllerian ducts are paired embryologic structures that undergo fusion and resorption in utero to give rise to the uterus, fallopian tubes, cervix, and upper two-thirds of the vagina. Interruption of normal development of the müllerian ducts can result in formation of müllerian duct anomalies (MDAs). MDAs are a broad and complex spectrum of abnormalities that are often associated with primary amenorrhea, infertility, obstetric complications, and endometriosis. MDAs are commonly associated with renal and other anomalies; thus, identification of both kidneys is important. However, MDAs are not associated with ovarian anomalies. Hysterosalpingography (HSG) is routinely used in evaluation of infertility. Because a key component of MDA characterization is the external uterine fundal contour, HSG is limited for this purpose. Patients suspected of having an MDA are often initially referred for pelvic ultrasonography (US). Magnetic resonance (MR) imaging is typically reserved for complex or indeterminate cases. MR imaging is the imaging standard of reference because it is noninvasive, does not involve ionizing radiation, has multiplanar capability, allows excellent soft-tissue characterization, and permits a greater field of interrogation than does US. Use of MR imaging for evaluation of MDAs reduces the number of invasive procedures and related costs by guiding management decisions.

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“…The sinus ridge may move by (i) differential growth of the urethra anterior and posterior to the sinus ridge, (ii) collective cell migration of the sinus ridge cells, or (iii) septation of the sinus ridge from the urethra in a rostral-to-caudal direction. Surprisingly little is known about the development of several components of the female reproductive tract, such as the hymen, Bartholin's gland, and Skene's gland (49). The Skene's gland in females has long been referred to as the homolog of the male prostate; however, the Skene's gland is positioned at the urethral orifice in females, which contrasts with the position of the prostate in the pelvic urethra in males (50,51).…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal dynamics of androgen signaling underlie sexual differentiation and congenital malformations of the urethra and vagina

Larkins

Enriquez

Cohn

2016

Proc. Natl. Acad. Sci. U.S.A.

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Disorders of sex development (DSDs) are congenital anomalies that affect sexual differentiation of genitourinary organs and secondary sex characters. A common cause of female genital virilization is congenital adrenal hyperplasia (CAH), in which excess androgen production during development of 46XX females can result in vaginal atresia, masculinization of the urethra, a single urogenital sinus, and clitoral hypertrophy or ambiguous external genitalia. Development of the vagina depends on sexual differentiation of the urogenital sinus ridge, an epithelial thickening that forms where the sex ducts attach to the anterior urethra. In females, the sinus ridge descends posteriorly to allow the vaginal opening to form in the vulva, whereas in males and in females with CAH, androgens inhibit descent of the sinus ridge. The mechanisms that regulate development of the female urethra and vagina are largely unknown. Here we show that the timing and duration of, and the cell population targeted by, androgen signaling determine the position of vaginal attachment to the urethra. Manipulations of androgen signaling in utero reveal a temporal window of development when sinus ridge fate is determined. Cell type-specific genetic deletions of androgen receptor (Ar) identify a subpopulation of mesenchymal cells that regulate sinus ridge morphogenesis. These results reveal a common mechanism that coordinates development of the vagina and feminization of the urethra, which may account for development of a single urogenital sinus in females exposed to excessive androgen during a critical period of prenatal development.vagina | urethra | androgen | mouse | development

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Vaginal Agenesis, the Hymen, and Associated Anomalies

Cited by 57 publications

References 28 publications

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

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

Imaging of Müllerian Duct Anomalies

Spatiotemporal dynamics of androgen signaling underlie sexual differentiation and congenital malformations of the urethra and vagina

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