PhD defence by Emilie Elmelund

Principal supervisor:

• Professor Terje Svingen

Co-supervisor:

• Postdoc Monica K. Draskau

Examiners:

• Senior researcher Martin S. Mortensen, DTU Food
• Professor David M. Kristensen, Roskilde University, Denmark
• Professor Paul A. Fowler, University of Aberdeen, United Kingdom

Chairperson at defence:

• Senior researcher Sofie Christiansen, DTU Food

Resume
Hypospadias, a genital malformation where the urethra opens on the underside of the penis, is one of the most common birth defects in boys, affecting up to 1 out of 125 male newborns. Worryingly, the incidence of hypospadias has been rising, and scientists suspect that one reason for this is increased exposure to environmental chemicals, especially those that disrupt the hormone system, so called endocrine disruptors. Fetal penis development is dependent on sex hormones and endocrine disruptors have been shown to cause hypospadias in laboratory animals. However, the molecular mechanisms linking chemical exposure to hypospadias are not well understood.

This PhD thesis characterizes how endocrine disruptors can cause hypospadias, using the rat as a model system. A range of advanced molecular biological techniques were used to examine hypospadias development at morphological, cellular, and gene expression level. Integration of these results show how development of hypospadias involves a complex network of biological processes and signaling pathways within specific cells. Notably, the results support a significant crosstalk between androgen and estrogen signaling, a relationship often overlooked in studies of male reproductive development.

The findings in this thesis provide important insights to the developmental effects of endocrine disruptors that can improve chemical risk and safety assessments and be used in development of new chemical test methods. Reliable and sensitive tools to evaluate endocrine disruptors are critical to protect human reproductive health.

A copy of the PhD thesis is available for reading at the department.