Infertility-Causing Haploinsufficiency Reveals TRIM28/KAP1 Requirement in Spermatogonia
| Autor: | Philipp Kaldis, Joel H.L. Tan, Daniel M. Messerschmidt, Ans M.M. van Pelt, Heike Wollmann |
|---|---|
| Přispěvatelé: | Center for Reproductive Medicine, Amsterdam Reproduction & Development (AR&D) |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Infertility endocrine system TRIM28 Regulator Tripartite Motif-Containing Protein 28 Biology Biochemistry Article Loss of heterozygosity Mice 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Epigenetics Infertility Male fertility spermatogonial stem cells Cell Biology medicine.disease Spermatogonia spermatogenesis haploinsufficiency Cell biology Mice Inbred C57BL 030104 developmental biology KAP1 Stem cell infertility Haploinsufficiency Spermatogenesis 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem cell reports, 14(5), 818-827. Cell Press Stem Cell Reports |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2020.03.013 |
| Popis: | Summary Spermatogenesis relies on exquisite stem cell homeostasis, the carefully balanced self-renewal and differentiation of spermatogonial stem cells (SSCs). Disturbing this equilibrium will likely manifest through sub- or infertility, a global health issue with often idiopathic presentation. In this respect, disease phenotypes caused by haploinsufficiency of otherwise vital developmental genes are of particular interest. Here, we show that mice heterozygous for Trim28, an essential epigenetic regulator, suffer gradual testicular degeneration. Contrary to previous reports we detect Trim28 expression in spermatogonia, albeit at low levels. Further reduction through Trim28 heterozygosity increases the propensity of SSCs to differentiate at the cost of self-renewal. Graphical Abstract Highlights • TRIM28/KAP1 haploinsufficiency causes testicular degeneration and infertility • TRIM28/KAP1 is expressed in spermatogonia stem cell compartment • Stem cell homeostasis in the testis is dependent on proper TRIM28/KAP1 levels In this article, Tan et al. show haploinsufficiency of TRIM28/KAP1 causes premature degeneration of the seminiferous epithelium in young adult mice. The requirement of proper TRIM28 levels is cell-autonomous and specific to spermatogonial stem cells, previously shown to be devoid of TRIM28 expression. They instead reveal Trim28’s vital role in spermatogonia to maintain proper stem cell homeostasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|