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The Almstrup Group

The Almstrup Group works at the intersection of genetics, epigenetics, and reproductive biology. We study how genetic and epigenetic variation, together with testicular gene expression and sperm cell function, influences reproductive outcomes


The Almstrup Group is part of the Department of Growth and Reproduction at Copenhagen University Hospital – Rigshospitalet, but is also affiliated with the Department of Cellular and Molecular Medicine, at the University of Copenhagen. Our research focuses on understanding how genetic and epigenetic variation affects human reproductive health and we also study testicular gene expression and sperm cell function to uncover biological mechanisms underlying male reproductive outcomes.

Genetic and epigenetic variation

The Almstrup group has been at the forefront of characterizing genetic and epigenetic variation associated with male reproductive health. We have identified genetic variants with significant effects on pubertal onset and demonstrated dynamic changes in DNA methylation that closely track pubertal development. In addition, the group has contributed to defining epigenetic signatures linked to key reproductive phenotypes.
The group actively participates in several international genetic consortia aimed at improving our understanding of testicular function and disease. These include:

The Genetics of Male Infertility Initiative (GEMINI) and the International Male Infertility Genomics Consortium (IMiGC), which aim to characterize the genetic basis of non‑obstructive azoospermia.

       

The Testis Cancer Consortium (TECAC), which seeks to identify genetic risk factors underlying testicular germ cell cancer.




Through these collaborative efforts, the Almstrup group contributes to advancing the genetic and epigenetic understanding of male reproductive development, infertility, and testicular disease.​

Profile papers: 

Small RNAs and testicular function

Small RNAs, including microRNAs (miRNAs) and PIWI‑interacting RNAs (piRNAs), constitute a major research focus of the Almstrup Group. We have demonstrated that piRNAs—small RNAs that are largely specific to male germ cells—are essential for normal human spermatogenesis. Furthermore, we have identified piRNAs in seminal plasma and in circulation, highlighting their potential as non‑invasive biomarkers of testicular function.
In addition to piRNAs, specific miRNAs have emerged as highly promising, sensitive biomarkers for testicular germ cell cancer. Together, these findings underscore the importance of small RNAs in male reproductive biology and their potential clinical utility in disease detection and monitoring.

Testicular gene expression and Single-Cell Profiling

The testis is a highly complex tissue composed of multiple distinct cell types. Studies of testicular gene expression must therefore account for cellular composition in order to generate biologically meaningful interpretations. The Almstrup group has been engaged in testicular gene expression research since the pre‑omics era, initially using differential display techniques, and has continuously adopted emerging technologies.
Currently, the group applies high‑throughput bulk and single‑cell approaches to study testicular biology. We have recently used RNA sequencing to characterize gene expression patterns in testicular tissue from men with Klinefelter syndrome (47,XXY) and employed single‑cell RNA sequencing to comprehensively profile human spermatogenesis. These studies provide insights into cell‑type‑specific transcriptional regulation in both normal and impaired testicular function​.

Profile papers: 

X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome. Death Dis. 2024;15(6):396.

The molecular evolution of spermatogenesis across mammals. Nature. 2023;613(7943):308-316.

Integration and reanalysis of transcriptomics and methylomics data derived from blood and testis tissue of men with 47,XXY Klinefelter syndrome indicates the primary involvement of Sertoli cells in the testicular pathogenesis. Am J Med Genet C Semin Med Genet. 2020;184(2):239-255.

Sperm cell function
Sperm cells are highly specialized cells characterized by a tightly packed haploid genome, extreme differentiation, and a singular biological purpose: fertilization of the oocyte. The Almstrup laboratory conducts research focused on sperm cell physiology and the development of next‑generation semen analysis techniques.

Our studies have demonstrated that the number of viable sperm cells with an intact acrosome is a critical determinant of male fertility. In addition, we have shown that environmental chemical exposures can directly impair sperm cell function. Together, these findings contribute to a more refined functional understanding of sperm quality beyond conventional semen parameters.

Current team members

Nina Mørup Nygaard, Sofia B. Winge, Ailsa Maria Main, Maria Lykkegaard Nicolaisen, Malene Asp Bock Mejdahl, Kirstine Lykke Jensen, Helle Margit Albrechtsen, Louise Holst Sørensen, Kirstine Lykke Jensen

Visiting scientists

Blanka Konieczna, Roberta Palazzo, Merve Tatli, María Cecilia Lardone, Simona Enoiu, Kishlay Kumar, Ghazal Alavioon, Rytis Stakaitis, Ieva Golubickaite. ​

Previous members

Gülizar Saritas, Mette Bjerg Lindhøj, Marie B. Nygaard, Pernille Norup, Dorte L. Egeberg Palme, Malte S. Nissen, Andreas C. Lawaetz, Dina Kristensen, Tine Hvarness, Olga Maria Culbreth, Fozia Jabeen Shah.

Key collaborators

Prof. Mikkel Schierup, Bioinformatics Research Centre, Aarhus University, DK.
Prof. Don Conrad, Department of Genetics, Washington University, USA.
Prof. Katherine L. Nathanson, University of Pennsylvania, USA.



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