Sex chromosome aneuploidies are conditions characterized by atypical numbers or arrangement of X and Y chromosomes, and can affect development, fertility, and physical traits. Klinefelter syndrome (47,XXY), 47,XYY syndrome, and 46,XX male syndrome (SRY⁺) are three well-known examples, each with distinct features. Mosaicism and disturbances in X-chromosome inactivation can also affect cell and organ function.
Our research is focused on understanding the consequences of sex chromosome aneuploidies on reproductive development and cell function, general health, and psychosocial wellbeing from infancy to adulthood.
Current team members
Lise Aksglæde, MD, PhD
Sofia Boeg Winge, MSc, PhD
Ida Dyhr Caspersen, MPsych, PhD, neuropsychologist
Andrés Felipe Østergaard Fritzbøger, MD, PhD-student
Cecilie Nexmann Larsen, MD, PhD-student
Anders Juul, Professor, head of department
Niels E. Skakkebæk, MD, Professor
Ewa Rajpert-De Meyts, MD, PhD, DMSc, Research Consultant
Jørgen Holm Petersen, Associate professor, PhD, Statistician
Visiting scientists
Hans Valdemar Lopéz Krabbe, MD, Sevilla, Spain
Riccardo Battiston, MD, Verona, Italy
Key publications
Skakkebaek NE. Two types of tubules containing only Sertoli cells in adults with Klinefelter's syndrome. Nature. 1969;223(5206):643-5.
Aksglaede L, Wikström AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update. 2006;12(1):39-48.
Ottesen AM*, Aksglaede L*… Rajpert-De Meyts E … Juul A. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy. Am J Med Genet A. 2010;152A(5):1206-12.
Aksglaede L, Skakkebaek NE, Almstrup K, Juul A. Clinical and biological parameters in 166 boys, adolescents and adults with nonmosaic Klinefelter syndrome: a Copenhagen experience. Acta Paediatr. 2011;100(6):793-806.
Winge SB… Aksglaede L … Skakkebæk NE, Juul A, Rajpert-De Meyts E, Almstrup K. Transcriptome analysis of the adult human Klinefelter testis and cellularity- matched controls reveals disturbed differentiation of Sertoli- and Leydig cells. Cell Death Dis. 2018 May 22;9(6):586.
López Krabbe HV … Juul A, Aksglaede L. Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome. Endocr Connect. 2023;12;12(7):e230031.
Winge SB, Skakkebaek NE, Aksglaede L, Saritas G, Rajpert-De Meyts E, Goossens E, Juul A, Almstrup K. X chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome. Cell Death Dis. 2024;15(6):396.
Funding sources
Novo Nordisk Foundation, Denmark
The Research Counsil at Rigshospitalet, Denmark
The Independent Research Fund, Denmark
Besins Healthcare, France (providing study drug for the TIPY study)
Current studies
Title: Klinefelter syndrome – the effect of Testosterone treatment in Puberty (The TIPY study)
The aim of this project is to evaluate the effect of two years testosterone treatment during puberty in boys with Klinefelter syndrome (47,XXY) aged 10-14 years. The study is a national, randomized, double-blind, placebo-controlled intervention study. ClinicalTrials.gov NCT06294990
Title: Long-term systematic follow-up of patients with Klinefelter syndrome followed at the Department of Growth and Reproduction, Rigshospitalet (FOXXY)
We aim to systematically describe the phenotype of Klinefelter syndrome throughout life by collecting clinical, biochemical, genetic and radiological data on reproductive development, fertility, anthropometry, bone age, body composition, bone mineralization, co-morbidities, and biomarkers of general health. ClinicalTrials.gov H-24071762
Title: X chromosome micro-mosaicism and Sertoli cell function
We have recently shown in Klinefelter syndrome that differentiation of the somatic Sertoli cell is incompatible with an extra X chromosome whereby a micro-mosaic X chromosome loss must occur in these cells to allow proper maturation. We aim to describe the timing, underlying mechanisms, and to explore whether the same occurs in 46,XX males.
Title: The role of X chromosomal genes in testicular function
The central role of the X chromosome in male fertility is highlighted by the fact that men with Klinefelter syndrome and 46,XX male syndrome are generally infertile and will only occasionally have spermatogenesis. We aim to describe protein- and miRNA-coding X chromosomal genes that are essential for spermatogenesis to understand why an extra X chromosome is detrimental to spermatogenesis.