![]() Zebrafish, medaka and tilapia belong to the two teleost fish taxa ( Acanthomorpha and Cypriniformes) having lost the stra8 gene, while stra8 has been identified in at least fourteen other teleost fish including Southern catfish ( Ictalurus punctatus) and three salmonids, but there is little information on stra8 functions in fish. As these fish still are able to successfully complete spermatogenesis despite lacking a stra8 gene, the functional relevance for stra8 in fish needs further investigation. ![]() Also in teleost fish which lack a stra8 gene ( Pasquier et al., 2016), RA signaling promotes spermatogenesis such as the differentiation of spermatogonia in zebrafish ( Crespo et al., 2019a), or the meiotic initiation in medaka ( Adolfi et al., 2016) and tilapia ( Feng et al., 2015). ![]() Retinoic acid (RA), a derivative of vitamin A, strongly up-regulates expression of Stra8 in mammalian germ cells which is critical for developmental transitions in spermatogenesis including entry into meiosis ( Endo et al., 2015). Considering that Stra8 transcripts were detectable already in undifferentiated spermatogonia in mice ( Zhou et al., 2008), STRA8 may have functions, although perhaps not critical ones, also during the early mitotic phase of spermatogenesis. STRA8 activates a broad transcriptional program in the mouse testis, that includes genes involved in the meiotic prophase, but also DNA replication and the G1-S cell cycle transition ( Kojima et al., 2019). In mammals the start of meiosis strictly depends on Stra8 ( Endo et al., 2015), and loss of this gene in mice leads to sterility in both males and females ( Baltus et al., 2006 Anderson et al., 2008). It appears that also in a fish species with a stra8 gene in the genome, the critical relevance this gene has attained for mammalian spermatogenesis is not yet given, although detrimental effects of the loss of stra8 were clearly visible during maturation. While loss of stra8 increased germ cell apoptosis during salmon spermatogenesis, crispants compensated this cell loss by an elevated production of spermatogenic cysts, and were able to produce functional sperm. Different from Stra8-deficient mammals, a large number of germ cells completed spermatogenesis, sperm was produced and fertilization rates were similar in WT and crispant males. Decreased expression was recorded for some genes expressed in differentiating spermatogonia including dmrt1 and ccnd2 or in spermatocytes, such as ccna1. Gene expression analysis revealed unchanged ( lin28a, ret) or reduced levels ( egr1, dusp4) of transcripts associated with undifferentiated spermatogonia. The production of spermatogenic cysts, on the other hand, increased in maturing stra8 crispants. In maturing stra8 crispants, the spermatogenetic tubuli were partially disorganized and displayed a sevenfold increase in germ cell apoptosis, in particular among type B spermatogonia and spermatocytes. We targeted the salmon stra8 gene with two gRNAs one of these were highly effective and produced numerous mutations in stra8, which led to a loss of wild-type (WT) stra8 expression in F0 salmon testis. As in mammals, stra8 expression was restricted to germ cells in the testis, transcript levels increased during the start of puberty, and decreased when blocking the production of retinoic acid. Here, we have examined the effects of removing stra8 on male fertility in Atlantic salmon. This gene is missing in a number of fish species, including medaka and zebrafish, but is present in the majority of fishes, including Atlantic salmon. 4Reproductive Biology Group, Division Developmental Biology, Department Biology, Science Faculty, Utrecht University, Utrecht, NetherlandsĮntering meiosis strictly depends on stimulated by retinoic acid 8 ( Stra8) gene function in mammals.3Institute of Marine Research, Research Group Reproduction and Developmental Biology, Matre Research Station, Matredal, Norway.2Institute of Marine Research, Research Group Reproduction and Developmental Biology, Austevoll Research Station, Storebø, Norway.1Institute of Marine Research, Research Group Reproduction and Developmental Biology, Bergen, Norway.Edvardsen 1, Birgitta Norberg 2, Per Gunnar Fjelldal 3, Tom J. Skaftnesmo 1†, Diego Crespo 1†, Lene Kleppe 1, Eva Andersson 1, Rolf B.
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