Gonadal and urogenital conditions

What are gonadal and urogenital conditions?

Development and function of the reproductive system is critical for sexual reproduction, as well as physical and emotional wellbeing of individuals. Male and female anatomical differences arise from the activity of genes and hormones during embryonic and postnatal development. The earliest step is sex determination, where the initially undifferentiated embryonic gonads typically develop into either a pair of testes or ovaries depending on whether XY or XX sex chromosomes were inherited.

The outcome of gonadal sex determination sets in motion the male or female pathway of reproductive tract development. Several steps during these processes can be disrupted, causing conditions/variations of reproductive development. These include:

  • XX or XY sex reversal (chromosomal sex differs to anatomical sex)
  • Anomalies of the urogenital system (urinary/reproductive tracts)
  • Gonadal dysgenesis (atypical gonadal development)
  • Primary ovarian insufficiency (loss of ovarian function before age 40).

In females, urogenital anomalies include incomplete or atypical development of the oviducts, uterus, cervix and upper vagina.

These conditions are often diagnosed around puberty when menstrual issues arise and can be associated with infertility or recurrent pregnancy loss. Associated kidney, skeletal, cardiovascular, and auditory malformations may require affected women to undergo specialised gynaecological, emotional, and overall health care throughout their lives.

What causes gonadal and urogenital conditions?

The majority of congenital conditions affecting the reproductive system remain unexplained, and both genetic and environmental factors are believed to play a role.

Cases with a genetic aetiology are caused by gene products that are unable to function properly during fetal development. This is due to DNA sequence variants that are either inherited or arise spontaneously during fertilisation or early embryonic development.

Through genomic studies, specific genes or chromosomal regions have been identified as causes of several gonadal or urogenital anomalies.

More challenging has been the investigation of environmental factors, including compounds that could interfere with hormone activity and affect the development of the reproductive system.

Overall, the lack of translational studies to define the molecular mechanisms and the function of genes regulating sex development has significantly contributed to our current gap in knowledge, and poses a major challenge for the diagnosis and management of reproductive conditions.

What gonadal and urogenital conditions research is being done at UQCCR?

At UQCCR, we are utilising genome-wide analyses, molecular biology approaches, and gene-editing strategies – including CRISPR – to model reproductive and sex development conditions in mice. The goal of our research is to:

  1. Identify the causes of these conditions;
  2. Define the role of the genes involved in the formation and differentiation of the reproductive system; and
  3. Understand how environmental factors, such as diet, may also interact with genes to cause variations or conditions of reproductive development.

Our team has established a genetic program for women affected by urogenital anomalies including Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome (aplasia/agenesis of uterus and vagina), and we have developed translational strategies to identify and functionally validate candidate genes. We have established the International Consortium for Müllerian Conditions, and through international collaboration, we are investigating the pathogenesis of uterine anomalies (Yale University, USA), and clinical care for women with complex gynaecological conditions (Montana State University, USA).

Research groups

Functional genomics and sex development (Pelosi Group)

Fast facts

  • Gonadal and urogenital conditions are very complex and present with a high degree of variability.
  • Differences of sex development are one of the most common congenital conditions, occurring in up to 1% of newborn babies.
  • Urogenital anomalies are present in 5.5% of the general female population, 8% of infertile women, 13.3% of women with miscarriages and 24.5% of those with both miscarriages and infertility.
  • Gonadal and urogenital anomalies represent a major health concern and a significant healthcare burden due to difficult clinical management and possible association with additional conditions including endometriosis, gonadal cancer, and infertility.