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Pelosi Group - Research

MRKH Syndrome and Müllerian Anomalies

The Müllerian ducts are embryonic structures that develop into the female reproductive tract, which comprises oviducts, uterus, cervix, and upper part of the vagina. Atypical development of the Müllerian ducts result in Müllerian anomalies, including – among others – uterus bicornuate, unicornuate, and didelphys. The most severe of which is known as Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome, which is characterized by the incomplete development of uterus and/or vagina. The aetiology of MRKH Syndrome and other Müllerian Anomalies is currently unknown.

Sex determination and development

When the gonads first appear during early embryogenesis, they are undifferentiated (also called bipotential gonads). Depending on the chromosomal sex (XX in females, and XY in males), a specific developmental program is activated leading to the differentiation of ovaries or testes. Disorders of sex development (DSD) – or intersex conditions – occur when such a complex program is not executed properly. The genetic and cellular events regulating gonadal development are still poorly understood, and currently 10% of 46,XX DSD (XX males) and 70% of 46,XY DSD (XY females) are unexplained. 

Premature menopause

Menopause occurs physiologically around 51 years of age. The ultimate determinant of menopause is the age-related decrease in number of ovarian primordial follicles, which contain the eggs and are also known as the ovarian reserve. Premature menopause ensues when the ovarian reserve is depleted earlier than expected. When menopause occurs before age 40, it is called primary ovarian insufficiency (POI), affecting 1% of the general female population. When menopause occurs between age 40 and 50, it is called premature ovarian aging (POA), which affects around 4-7% of women. To date, the cause of POI remains unknown in 90% of cases.

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