Meiotic failure in male mice lacking an X-linked factor

Fang, Yang; Gell, Katarina; Heijden, Godfried W. van der; Eckardt, Sigrid; Leu, N. Adrian; Page, David C.; Benavente, Ricardo; Her, Chengtao; Höög, Christer; McLaughlin, K. John; Wang, Peijing Jeremy

doi:10.1101/gad.1613608

Cited by 159 publications

(208 citation statements)

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“…For histology, testes were fixed in Bouin's solution overnight, dehydrated in ethanol, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Surface-spread analysis of spermatocyte nuclei and immunofluorescence analyses of testis sections were described previously (37).…”

Section: Methodsmentioning

confidence: 99%

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Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway

Zheng

Xiol

Reuter

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Piwi-interacting RNAs (piRNAs) are essential for silencing of transposable elements in the germline, but their biogenesis is poorly understood. Here we demonstrate that MOV10L1, a germ cell-specific putative RNA helicase, is associated with Piwi proteins. Genetic disruption of the MOV10L1 RNA helicase domain in mice renders both MILI and MIWI2 devoid of piRNAs. Absence of a functional piRNA pathway in Mov10l1 mutant testes causes loss of DNA methylation and subsequent derepression of retrotransposons in germ cells. The Mov10l1 mutant males are sterile owing to complete meiotic arrest. This mouse mutant expresses Piwi proteins but lacks piRNAs, suggesting that MOV10L1 is required for piRNA biogenesis and/or loading to Piwi proteins.T he Piwi clade of Argonaute proteins associates with a class of 26-31-nt germline-specific small RNAs called "piRNAs". Together they participate in suppression of transposable elements in all animals studied (1-4). In mice, the Piwi clade contains three members: Miwi2, Mili, and Miwi. These three Piwi members exhibit distinct developmental expression patterns. Miwi2 is expressed in perinatal male germ cells (5), whereas Mili is more broadly expressed from embryonic germ cells to postnatal round spermatids (6). Miwi expression begins in pachytene spermatocytes and persists in haploid round spermatids (7). The overlapping temporal expression of Mili with Miwi and Miwi2 points to the pivotal role of MILI in the piRNA pathway, as further supported by the fact that MILI is associated with developmental stage-dependent pools of piRNAs: prenatal, prepachytene, and pachytene piRNAs (5,8,9).The mechanisms of piRNA biogenesis are largely unclear (1-4). One feature of piRNAs in all species is their highly clustered genomic origins. Several of these clusters produce piRNAs only from one strand. This leads to a hypothesized primary processing pathway whereby an unknown nuclease cleaves off mature piRNAs from a long single-stranded precursor transcript. On the other hand, some piRNAs in prenatal and prepachytene pools display signatures indicative of a proposed RNA-mediated amplification loop that uses primary piRNAs to generate secondary piRNAs from precursor transcripts (ping-pong mechanism) (10, 11). Apart from the Piwi proteins themselves, factors directly impacting piRNA production are unknown.We previously identified Mov10l1 as a gene specifically expressed in mouse germ cells, which encodes a putative RNA helicase of unknown function (12). Whereas the N-terminal half of MOV10L1 is not homologous to any other mouse proteins, its C-terminal RNA helicase domain exhibits low homology (45% amino acid identity) with MOV10. MOV10, the vertebrate homolog of Drosophila Armi, is ubiquitously expressed. In mammalian cells, MOV10 is associated with Argonaute proteins in the RNA-induced silencing complex (RISC) and is functionally required for RNA interference (13, 14). Here we demonstrate that MOV10L1 is an essential factor in the piRNA pathway. Results MOV10L1 Is Associated with Piwi Proteins.To identi...

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Section: Methodsmentioning

confidence: 99%

“…V6.5 ES cells were electroporated with linearized Mov10l1 targeting construct (pKe16-1/ClaI). Screening of ES cells was described previously (37). Two ES cell clones (A1 and B10) harboring the Mov10l1 fl allele were injected into B6C3F1 (Taconic) blastocysts.…”

Section: Methodsmentioning

confidence: 99%

Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway

Zheng

Xiol

Reuter

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

204

265

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“…It regulates homologous chromosome synapsis and double‐strand DNA breakage repair. Thus, it is critical for synaptonemal complex and chiasma formation during chromosomal cross‐over 103, 104, 105, 106. The protein is highly conserved and functionally uniform across species 103.…”

Section: Culprit Genes That Have Been Identified In the X Chromosomementioning

confidence: 99%

Human male infertility and its genetic causes

Miyamoto

Minase

Shin

et al. 2017

Reprod Medicine & Biology

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BackgroundInfertility affects about 15% of couples who wish to have children and half of these cases are associated with male factors. Genetic causes of azoospermia include chromosomal abnormalities, Y chromosome microdeletions, and specific mutations/deletions of several Y chromosome genes. Many researchers have analyzed genes in the AZF region on the Y chromosome; however, in 2003 the SYCP3 gene on chromosome 12 (12q23) was identified as causing azoospermia by meiotic arrest through a point mutation.MethodsWe mainly describe the SYCP3 and PLK4 genes that we have studied in our laboratory, and add comments on other genes associated with human male infertility.ResultsUp to now, The 17 genes causing male infertility by their mutation have been reported in human.ConclusionsInfertility caused by nonobstructive azoospermia (NOA) is very important in the field of assisted reproductive technology. Even with the aid of chromosomal analysis, ultrasonography of the testis, and detailed endocrinology, only MD‐TESE can confirm the presence of immature spermatozoa in the testes. We strongly hope that these studies help clinics avoid ineffective MD‐TESE procedures.

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“…crossovers, leading to infertility in males. 6 Interestingly, another study reported that the deficiency of Tex11 led to impaired crossover and achiasmate chromosomes at Meiosis I; however, males were fertile. 5 This discrepancy in phenotype could be attributed to the differential efficiency of gene knockout (a null allele vs. a hypomorphic allele), given that only one exon (exon3) was conditionally deleted in the Tex11 knockout animal in the second study.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 The TEX11 protein was found to form discrete foci along the synaptonemal complexes (SCs) on meiotic chromosomes and was shown to be essential for meiosis in males. 6 The conditional deletion of 27 exons (out of a total of 30 exons) of Tex11 in mice resulted in defects in synapsis formation and meiotic testis expressed gene 11 (Tex11) is essential for meiosis and male fertility in the mouse. Currently, little is known about the control of spermatogenesis in non-rodent animal models such as pigs.…”

Section: Introductionmentioning

confidence: 99%