Stimulated by retinoic acid gene 8 (Stra8) plays important roles in many stages of spermatogenesis

Ma, Haitao; Niu, Changmin; Xia, Jing; Shen, Xueyi; Xia, Mengmeng; Hu, Yanqiu; Zheng, Ying

doi:10.4103/aja.aja_26_18

Cited by 27 publications

(4 citation statements)

References 43 publications

(57 reference statements)

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“…RNA-seq data of Prmt1 KO testes revealed that the expression levels of major genes involved in the different stages of meiosis were downregulated in the absence of PRMT1 in male germ cells ( Figure 4 A), suggesting some severe defects at the time of meiosis in the Prmt1 KO germ cells. To investigate this possibility, we first checked the expression of STRA8, a marker of meiosis initiation [ 46 , 47 ] on P10 and found that there was negligible expression of STRA8 in Prmt1 KO testis ( Figure 4 B). We further exlpored the stage at which meiosis gets arrested in the KO testes by examining the expression of germ cell nuclear antigen 1 (GCNA1) in Prmt1 KO testes on P14 ( Figure S2 ).…”

Section: Resultsmentioning

confidence: 99%

Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells

Waseem

Kumar

Lee

et al. 2021

IJMS

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Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells; however, its function in vivo is not well understood due to its early embryonic lethality in null mice exhibiting spontaneous DNA damage, cell cycle delays, and defects in check point activation. Here, we generated germ cell-specific Prmt1 knock-out (KO) mice to evaluate the function of PRMT1 in spermatogenesis. Our findings demonstrate that PRMT1 is vital for male fertility in mice. Spermatogenesis in Prmt1 KO mice was arrested at the zygotene-like stage of the first meiotic division due to an elevated number of DNA double-strand breaks (DSBs). There was a loss of methylation in meiotic recombination 11 (MRE11), the key endonuclease in MRE11/RAD50/NBS 1 (MRN) complex, resulting in the accumulation of SPO11 protein in DSBs. The ATM-mediated negative feedback control over SPO11 was lost and, consequently, the repair pathway of DSBs was highly affected in PRMT1 deficient male germ cells. Our findings provide a novel insight into the role of PRMT1-mediated asymmetric demethylation in mouse spermatogenesis.

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Section: Resultsmentioning

confidence: 99%

Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells

Waseem

Kumar

Lee

et al. 2021

IJMS

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“…PRDM9 is a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and Prdm9-deficient mice are sterile (Parvanov et al, 2010). STRA8 directly modulated Prdm9 gene expression in mice (Ma et al, 2018;Kojima et al, 2019). PRDM9 interacts with SPO11, initiating DNA double-strand breaks (DSBs) that are repaired by the recombinases DMC1 and RAD51 in the meiosis crossover process (Parvanov et al, 2010;Grey et al, 2018;Paiano et al, 2020).…”

Section: Expressional Changes Associated With Meiosis and Spermiogenesismentioning

confidence: 99%

Loss of stra8 Increases Germ Cell Apoptosis but Is Still Compatible With Sperm Production in Atlantic Salmon (Salmo salar)

Skaftnesmo

Crespo

Kleppe

et al. 2021

Front. Cell Dev. Biol.

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Entering meiosis strictly depends on stimulated by retinoic acid 8 (Stra8) gene function in mammals. 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. Here, we have examined the effects of removing stra8 on male fertility in Atlantic salmon. 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. 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. 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. The production of spermatogenic cysts, on the other hand, increased in maturing stra8 crispants. Gene expression analysis revealed unchanged (lin28a, ret) or reduced levels (egr1, dusp4) of transcripts associated with undifferentiated spermatogonia. Decreased expression was recorded for some genes expressed in differentiating spermatogonia including dmrt1 and ccnd2 or in spermatocytes, such as ccna1. 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. 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. 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.

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“…A study showed, however, that c-KIT positive and c-KIT negative cultured germ cells displayed comparable SSC activity after transplantation [ 8 ]. On the other hand, stimulated by retinoic acid gene 8 ( Stra8 ), which is the receptor for retinoic acid and a key molecule in initiating meiosis [ 9 ], also plays a role in SSC maintenance, proliferation and self-renewal [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Evidence underlines the key role of ubiquitination in the derivation of SSCs and differentiation of spermatogonia from gonocytes [ 11 ], in genetic recombination [ 12 ] and in sex chromosome silencing during meiosis [ 13 ]. Ubiquitination is a post-translational modification that regulates several cellular processes such as protein turnover, DNA damage response and intracellular signaling [ 10 , 11 , 12 ], which can be reversed through the action of de-ubiquitinase enzymes [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Loss of Ubiquitin Carboxy-Terminal Hydrolase L1 Impairs Long-Term Differentiation Competence and Metabolic Regulation in Murine Spermatogonial Stem Cells

Alpaugh

Voigt

Dardari

et al. 2021

Cells

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Spermatogonia are stem and progenitor cells responsible for maintaining mammalian spermatogenesis. Preserving the balance between self-renewal of spermatogonial stem cells (SSCs) and differentiation is critical for spermatogenesis and fertility. Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) is highly expressed in spermatogonia of many species; however, its functional role has not been identified. Here, we aimed to understand the role of UCH-L1 in murine spermatogonia using a Uch-l1−/− mouse model. We confirmed that UCH-L1 is expressed in undifferentiated and early-differentiating spermatogonia in the post-natal mammalian testis. The Uch-l1−/− mice showed reduced testis weight and progressive degeneration of seminiferous tubules. Single-cell transcriptome analysis detected a dysregulated metabolic profile in spermatogonia of Uch-l1−/− compared to wild-type mice. Furthermore, cultured Uch-l1−/− SSCs had decreased capacity in regenerating full spermatogenesis after transplantation in vivo and accelerated oxidative phosphorylation (OXPHOS) during maintenance in vitro. Together, these results indicate that the absence of UCH-L1 impacts the maintenance of SSC homeostasis and metabolism and impacts the differentiation competence. Metabolic perturbations associated with loss of UCH-L1 appear to underlie a reduced capacity for supporting spermatogenesis and fertility with age. This work is one step further in understanding the complex regulatory circuits underlying SSC function.

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Stimulated by retinoic acid gene 8 (Stra8) plays important roles in many stages of spermatogenesis

Cited by 27 publications

References 43 publications

Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells

Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells

Loss of stra8 Increases Germ Cell Apoptosis but Is Still Compatible With Sperm Production in Atlantic Salmon (Salmo salar)

Loss of Ubiquitin Carboxy-Terminal Hydrolase L1 Impairs Long-Term Differentiation Competence and Metabolic Regulation in Murine Spermatogonial Stem Cells

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