ORIGINAL ARTICLE Ubiquitin-specific protease 26 (USP26) is not essential for mouse gametogenesis and fertility Natalia Felipe-Medina 1 & Laura Gómez-H 1 & Yazmine B. Condezo 1 & Manuel Sanchez-Martín 2,3 & José Luis Barbero 4 & Isabel Ramos 1 & Elena Llano 1,5 & Alberto M. Pendás 1 Received: 24 October 2018 /Revised: 18 February 2019 /Accepted: 22 February 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Ubiquitin-specific protease 26 (USP26) is a deubiquitylating enzyme belonging to the USPs family with a transcription pattern restricted to the male germline. Since protein ubiquitination is an essential regulatory mechanism during meiosis, many efforts have been focused on elucidating the function of USP26 and its relationship with fertility. During the last decade, several studies have reported the presence of different polymorphisms in USP26 in patients with non-obstructive azoospermia (NOA) or severe oligozoospermia suggesting that this gene may be associated with human infertility. However, other studies have revealed the presence of these and novel polymorphisms, including nonsense mutations, in men with normal spermatogenesis as well. Thus, the results remain controversial and its function is unknown. In the present study, we describe the in vivo functional analysis of mice lacking USP26. The phenotypic analysis of two different Usp26-null mutants showed no overt-phenotype with both males and females being fertile. Cytological analysis of spermatocytes showed no defects in synapsis, chromosome dynamics, DNA repair, or recombination. Histopathological analysis revealed a normal distribution and number of the different cell types in both male and female mice. Finally, normal counts were observed in fertility assessments. These results represent the first in vivo evidence showing that USP26 is not essential for mouse gametogenesis. Keywords Fertility . Spermatogenesis . Ubiquitination . Meiosis . Ubiquitin-specific protease Introduction Infertility is a major health issue with an estimated 8–12% of couples affected worldwide (Ombelet et al. 2008; Prieto et al. 2004). Men contribute to 50% and are solely responsible for 20–30% of reported cases (Sharlip et al. 2002). Many factors have been associated with male infertility such as environ- mental or occupational exposures and genetic abnormalities. Genetic causes are thought to underlie 15–30% of male infer- tilities being non-obstructive azoospermia (NOA), the com- plete absence of spermatozoa in the ejaculate due to a testic- ular failure, the most common outcome associated (Ferlin et al. 2007). Although chromosomal aberrations and microdeletions of the Y chromosome have been largely con- sidered to be the main cause of genetic male infertility (Matzuk and Lamb 2008; Reijo et al. 1996), in the past de- cades, a large number of fertility-related genes have been iden- tified through the analysis of mouse models, clinical cases, and genome-wide association studies (Caburet et al. 2014; Gomez et al. 2016; Hu et al. 2011). However, much work remains to be done as idiopathic azoospermia is still the most This article is part of a Special Issue on Recent advances in meiosis from DNA replication to chromosome segregation" edited by Valérie Borde and Francesca Cole, co-edited by Paula Cohen and Scott Keeney". Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00412-019-00697-6) contains supplementary material, which is available to authorized users. * Alberto M. Pendás amp@usal.es 1 Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca), 37007 Salamanca, Spain 2 Departamento de Medicina, Universidad de Salamanca, Salamanca 37007, Spain 3 Transgenic Facility, Nucleus platform, Universidad de Salamanca, Salamanca 37007, Spain 4 Departamento de Biología Celular y Molecular, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain 5 Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca 37007, Spain Chromosoma https://doi.org/10.1007/s00412-019-00697-6