Emi2 Is Essential for Mouse Spermatogenesis

Gopinathan, Lakshmi; Szmyd, Radosław; Low, Diana; Diril, M. Kasim; Chang, Hui-Ming; Coppola, Vincenzo; Liu, Kui; Tessarollo, Lino; Guccione, Ernesto; Pelt, Ans M.M. van; Kaldis, Philipp

doi:10.1016/j.celrep.2017.06.033

Cited by 47 publications

(48 citation statements)

References 68 publications

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“…6E) (24). Spermatocytes lacking CCNA1 or EMI2 exhibit meiotic arrest at the diplotene stage (25,31). However, pachytene spermatocytes from neither of these mutant (Ccna1 or Emi2) mice undergo premature chromosome desynapsis, suggesting that these factors regulate PI/MI transition but not MI competence acquisition.…”

Section: Discussionmentioning

confidence: 99%

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SKP1 drives the prophase I to metaphase I transition during male meiosis

Guan

Leu

et al. 2020

Sci. Adv.

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The meiotic prophase I to metaphase I (PI/MI) transition requires chromosome desynapsis and metaphase competence acquisition. However, control of these major meiotic events is poorly understood. Here, we identify an essential role for SKP1, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin E3 ligase, in the PI/MI transition. SKP1 localizes to synapsed chromosome axes and evicts HORMAD proteins from these regions in meiotic spermatocytes. SKP1-deficient spermatocytes display premature desynapsis, precocious pachytene exit, loss of PLK1 and BUB1 at centromeres, but persistence of HORMAD, H2AX, RPA2, and MLH1 in diplonema. Strikingly, SKP1-deficient spermatocytes show sharply reduced MPF activity and fail to enter MI despite treatment with okadaic acid. SKP1deficient oocytes exhibit desynapsis, chromosome misalignment, and progressive postnatal loss. Therefore, SKP1 maintains synapsis in meiosis of both sexes. Furthermore, our results support a model where SKP1 functions as the long-sought intrinsic metaphase competence factor to orchestrate MI entry during male meiosis. , SKP1 drives the prophase I to metaphase I transition during male meiosis.

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Section: Discussionmentioning

confidence: 99%

“…Early meiotic inhibitor 2 (EMI2), an inhibitor of the anaphase-promoting complex APC/C, was also absent in Skp1 cKO testes (Fig. 6B) (25). OA induces chromosomal desynapsis in pachynema and entry into MI in WT spermatocytes (Fig.…”

Section: Skp1 Is Essential For Mpf Activity and MI Entry In Spermatocmentioning

confidence: 91%

SKP1 drives the prophase I to metaphase I transition during male meiosis

Guan

Leu

et al. 2020

Sci. Adv.

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“…The essential role of FBXO43 is as a cytostatic factor component that is required for maintenance of metaphase II arrest in mouse oocytes (10,11). In female FBXO43 knockout mice, oocytes exhibit defective entry into meiosis II (12). Moreover, FBXO43 is also essential for spermatocytes to complete meiotic divisions in mice (12).…”

mentioning

confidence: 99%

“…In female FBXO43 knockout mice, oocytes exhibit defective entry into meiosis II (12). Moreover, FBXO43 is also essential for spermatocytes to complete meiotic divisions in mice (12). In male FBXO43 knockout mice, spermatocytes cannot complete meiotic divisions, and spermatids are absent in the testes (12).…”

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A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family

Xie²,

Dong-yang

et al. 2019

Fertility and Sterility

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Objective: To identify the genetic causes of male infertility characterized by teratozoospermia. Design: Genetic studies. Setting: Medical university. Patient(s): Two infertile brothers with teratozoospermia in a consanguineous Chinese family, another 124 sporadic infertile male patients presenting with teratozoospermia, and 200 male controls with normal fertility. Invention(s): None. Main Outcome Measure(s): Whole exome sequencing and genotype analysis to identify the potential pathogenic mutation, Sanger sequencing to validate the mutation in family members, in silico structural modeling to predict the functional consequences of mutation, and targeted next-generation sequencing to validate the mutation in sporadic cases. Result(s): A novel homozygous nonsynonymous mutation (C1991T, p.G664D) in FBXO43 (F-box only protein 43) was observed in two brothers from a consanguineous Chinese family. The mutation was segregated with the disease phenotype and was predicted to be a disease causing protein by SIFT, PolyPhen-2, and Mutation Taster. An in silico mutant FBXO43 model predicts that the mutation p.G664D causes shortening of two b-sheets, an additional a-helix, and change in loops, which may result in loss of function of the protein. The homozygous mutation of FBXO43 was absent in the 1000 Genomes Project (1000 G) and the Exome Aggregation Consortium (ExAC) databases. Subsequent mutation screening of FBXO43 in a cohort of 124 cases identified four additional cases with heterozygous FBXO43 mutations. No mutations were found in FBXO43 in 200 fertile controls. Conclusion(s): The mutation in FBXO43 is a causative factor of male infertility and teratozoospermia.

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Diverse roles for CDK‐associated activity during spermatogenesis

2019

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The primary function of cyclin‐dependent kinases (CDKs) in complex with their activating cyclin partners is to promote mitotic division in somatic cells. This canonical cell cycle‐associated activity is also crucial for fertility as it allows the proliferation and differentiation of stem cells within the reproductive organs to generate meiotically competent cells. Intriguingly, several CDKs exhibit meiosis‐specific functions and are essential for the completion of the two reductional meiotic divisions required to generate haploid gametes. These meiosis‐specific functions are mediated by both known CDK/cyclin complexes and meiosis‐specific CDK‐regulators and are important for a variety of processes during meiotic prophase. The majority of meiotic defects observed upon deletion of these proteins occur during the extended prophase I of the first meiotic division. Importantly a lack of redundancy is seen within the meiotic arrest phenotypes described for many of these proteins, suggesting intricate layers of cell cycle control are required for normal meiotic progression. Using the process of male germ cell development (spermatogenesis) as a reference, this review seeks to highlight the diverse roles of selected CDKs their activators, and their regulators during gametogenesis.

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Emi2 Is Essential for Mouse Spermatogenesis

Cited by 47 publications

References 68 publications

SKP1 drives the prophase I to metaphase I transition during male meiosis

SKP1 drives the prophase I to metaphase I transition during male meiosis

A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family

Diverse roles for CDK‐associated activity during spermatogenesis

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