Almstrup Group

Genetic and epigenetic variation

The Almstrup group has been pioneering in describing genetic and epigenetic variation associated with several reproductive endpoints. This includes genetic variants causing non-obstructive azoospermia (GEMINI, IMIGC consortia), genetic variants associated with testicular germ cell cancer (TECAC consortia) as well as genetic variants and DNA methylation patterns that have a significant effect on the age of pubertal onset.

Small RNAs

Small RNAs, like micro RNAs (miRNAs) and the PIWI-interacting RNAs (piRNAs), is an area of great interest to our group. We have shown that the piRNAs, which are nearly unique to male germ cell, are essential for human spermatogenesis and have identified piRNAs in seminal plasma and in circulation that may serve as markers of testicular function. However, also specific miRNAs show great promise as novel sensitive biomarker of testicular germ cell cancer.

Testicular gene expression

The testis is a complex tissue with many different cell types and studies of testicular gene expression, therefore, needs to take into account the composition of cell types that are present in the analysis. The Almstrup group has been involved in studies of testicular gene expression since the pre-omics era, using differential display techniques, and are now working with single-cell/nuclei methods and spatial transcriptomics.

Sperm cell function

Sperm cells are unique because they have a tightly packed haploid genome, are extremely differentiated, and has the sole purpose of fertilising an egg. We have shown that the number of viable sperm cells with an intact acrosome is important for the fertility of men and that environmental chemicals can influence sperm cell function directly.

• Nagirnaja, L., Mørup, N., Nielsen, J. E., Stakaitis, R., Golubickaite, I., Oud, M. S., Winge, S. B., Carvalho, F., Aston, K. I., Khani, F., Van Der Heijden, G. W., Marques, C. J., Skakkebæk, Niels Erik, Rajpert–de Meyts, E., Schlegel, P. N., Jørgensen, N., Veltman, J. A., Lopes, A. M., Conrad, D. F. & Almstrup, K (2021). Variant PNLDC1, Defective piRNA Processing, and Azoospermia. New England Journal of Medicine, 385(8), 707-719.
• Nagirnaja, L., Lopes, A. M., Charng, W., Miller, B., Stakaitis, R., Golubickaite, I., Stendahl, A., Luan, T., Friedrich, C., Mahyari, E., Fadial, E., Kasak, L., Vigh-Conrad, K., Oud, M. S., Xavier, M. J., Cheers, S. R., James, E. R., Guo, J., Jenkins, T. G., Riera-Escamilla, A., Barros, A., Carvalho, F., Fernandes, S., Gonçalves, J., Gurnett, C. A., Jørgensen, N., Jezek, D., Jungheim, E. S., Kliesch, S., McLachlan, R. I., Omurtag, K. R., Pilatz, A., Sandlow, J. I., Smith, J., Eisenberg, M. L., Hotaling, J. M., Jarvi, K. A., Punab, M., Rajpert-De Meyts, E., Carrell, D. T., Krausz, C., Laan, M., O'Bryan, M. K., Schlegel, P. N., Tüttelmann, F., Veltman, J. A., Almstrup, K., Aston, K. I. & Conrad, D. F. (2022). Diverse monogenic subforms of human spermatogenic failure. Nature Communications, 13(1):7953.
• Murat, F., Mbengue, N., Winge, S. B., Trefzer, T., Leushkin, E., Sepp, M., Cardoso-Moreira, M., Schmidt, J., Schneider, C., Mößinger, K., Brüning, T., Lamanna, F., Belles, M. R., Conrad, C., Kondova, I., Bontrop, R., Behr, R., Khaitovich, P., Pääbo, S., Marques-Bonet, T., Grützner, F., Almstrup, K., Schierup, M. H. & Kaessmann (2022). The molecular evolution of spermatogenesis across mammals. Nature (online ahead of print).
• Skakkebæk, NE, Lindahl-Jacobsen, R., Levine, H., Andersson, A., Jørgensen, N., Main, KM., Lidegaard, O., Priskorn, L., Holmboe, S. A., Bräuner, E. V., Almstrup, K., Franca, L. R., Znaor, A., Kortenkamp, A., Hart, R. J. & Juul, A. (2022). Environmental factors in declining human fertility. Nature Reviews Endocrinology, 18(3):139-157.
• Pluta J, Pyle LC, Nead KT, Wilf R, Li M, Mitra N, Weathers B, D'Andrea K, Almstrup K, Anson-Cartwright L, Benitez J, Brown CD, Chanock S, Chen C, Cortessis VK, Ferlin A, Foresta C, Gamulin M, Gietema JA, Grasso C, Greene MH, Grotmol T, Hamilton RJ, Haugen TB, Hauser R, Hildebrandt MAT, Johnson ME, Karlsson R, Kiemeney LA, Lessel D, Lothe RA, Loud JT, Loveday C, Martin-Gimeno P, Meijer C, Nsengimana J, Quinn DI, Rafnar T, Ramdas S, Richiardi L, Skotheim RI, Stefansson K, Turnbull C, Vaughn DJ, Wiklund F, Wu X, Yang D, Zheng T, Wells AD, Grant SFA, Rajpert-De Meyts E, Schwartz SM, Bishop DT, McGlynn KA, Kanetsky PA, Nathanson KL; Testicular Cancer Consortium. (2021). Identification of 22 susceptibility loci associated with testicular germ cell tumors. Nature Communications, 12(1):4487.
• Almstrup, Kristian, Lobo, J., Mørup, N., Belge, G., Rajpert-De Meyts, E., Looijenga, L. H. J. & Dieckmann, K. P. (2020) Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours. Nature Reviews Urology, 17(4):201-213