Title of project

Sex Chromosome Aneuploidies: From Hypogonadism to Hormone Replacement Therapy Response

Abstract

The sex chromosome aneuploidies Turner syndrome (45,X; TS) and Klinefelter syndrome (47,XXY; KS) are characterized by hypergonadotropic hypogonadism and infertility, often accompanied by unfavorable changes in body composition and an increased risk of metabolic and cardiovascular disease. To alleviate these detrimental effects, patients are offered hormone replacement therapy. While positively influencing several aspects of the disease pattern, not all effects are normalized. It is currently unknown what causes the hypogonadism, how metabolic tissues respond to long-standing hypogonadism and treatment, and why the treatment response is incomplete.
This study aims to investigate these effects on the molecular level. By combining cutting-edge, high-resolution genetic methodologies with functional studies of stem cells, we specifically wish to investigate (i) hypogonadal pathogenesis and infertility from gonadal tissues, and (ii) the consequences of long-standing hypogonadism and response to hormone replacement therapy from skeletal muscle and adipose tissue. Not only can this project significantly improve our understanding of hypogonadism and guide treatment of patients with sex chromosome aneuploidies – it can also provide a broader understanding of infertility, hypogonadism and sex hormones in the general population.