MTCH2 is differentially expressed in rat testis and mainly related to apoptosis of spermatocytes

Goldman, Andrés; Rodríguez-Casuriaga, Rosana; González-López, Evangelina; Capoano, Carlos A.; Santiñaque, Federico F.; Geisinger, Adriana

doi:10.1007/s00441-015-2163-2

Cited by 10 publications

(9 citation statements)

References 54 publications

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“…SDS-polyacrylamide gel electrophoresis was carried out on 12% polyacrylamide gels. Protein gels were transferred to nitrocellulose membranes as instructed [54], and Western blots were performed as previously described [55]. Membranes were incubated for 2 h at room temperature in TBST with primary antibodies (anti-SYCE1-Nt and anti-βtubulin), and for 1 h in blocking solution with anti-rabbit secondary antibody.…”

Section: Western Blotsmentioning

confidence: 99%

Familial primary ovarian insufficiency associated with an SYCE1 point mutation: defective meiosis elucidated in humanized mice

Hernández-López

Geisinger

Trovero

et al. 2020

Molecular Human Reproduction

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Abstract More than 50% of cases of primary ovarian insufficiency (POI) and nonobstructive azoospermia in humans are classified as idiopathic infertility. Meiotic defects may relate to at least some of these cases. Mutations in genes coding for synaptonemal complex (SC) components have been identified in humans, and hypothesized to be causative for the observed infertile phenotype. Mutation SYCE1 c.721C>T (former c.613C>T)—a familial mutation reported in two sisters with primary amenorrhea—was the first such mutation found in an SC central element component-coding gene. Most fundamental mammalian oogenesis events occur during the embryonic phase, and eventual defects are identified many years later, thus leaving few possibilities to study the condition’s etiology and pathogenesis. Aiming to validate an approach to circumvent this difficulty, we have used the CRISPR/Cas9 technology to generate a mouse model with an SYCE1 c.721C>T equivalent genome alteration. We hereby present the characterization of the homozygous mutant mice phenotype, compared to their wild type and heterozygous littermates. Our results strongly support a causative role of this mutation for the POI phenotype in human patients, and the mechanisms involved would relate to defects in homologous chromosome synapsis. No SYCE1 protein was detected in homozygous mutants and Syce1 transcript level was highly diminished, suggesting transcript degradation as the basis of the infertility mechanism. This is the first report on the generation of a humanized mouse model line for the study of an infertility-related human mutation in an SC component-coding gene, thus representing a proof of principle.

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Section: Western Blotsmentioning

confidence: 99%

Familial primary ovarian insufficiency associated with an SYCE1 point mutation: defective meiosis elucidated in humanized mice

Hernández-López

Geisinger

Trovero

et al. 2020

Molecular Human Reproduction

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“…Exposing the testes of mice [ 4 ], rats [ 5 , 6 ], monkeys [ 7 ], bulls [ 8 ], sheep [ 9 ], and humans [ 10 , 11 ] to high temperatures induced germ cell apoptosis in spermatogenesis [ 12 ]. Heat stress in the scrotum induced the apoptosis of germ cells [ 13 – 16 ], imbalances in antioxidant levels leading to oxidative stress [ 17 – 19 ], and deregulation in the gene expression pattern [ 20 ]. Comparative proteomics of testis biopsy specimens of men subjected to transient scrotal hyperthermia has revealed that these deregulated proteins were associated with germ cell proliferation and apoptosis [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of transient scrotal hyperthermia on human sperm: an iTRAQ-based proteomic analysis

Rao

et al. 2020

Reprod Biol Endocrinol

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Background Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm. Methods Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography–tandem mass spectrometry. Results In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia. Conclusions The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.

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“…The results showed that the SiNPs signi cantly increased the protein expression of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3, which suggested that the SiNPs activated the MTCH2 and mitochondrial apoptosis signaling pathway in vivo. MTCH2, a mitochondrial outer membrane protein (24), was mostly related to the apoptosis of spermatocytes (20). It was reported that MTCH2 could facilitate the recruitment of the truncated BID to mitochondria (24).…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that mitochondrial carrier homolog 2 (MTCH2) is a mitochondrial outer membrane protein that is essential for embryonic development (19). Recent research has shown that MTCH2 is highly expressed in rat testis and primarily related to the apoptosis of spermatocytes (20). Based on the above studies, the present study was designed to rstly investigate the effects of SiNPs on the expressions of miR-450b-3p, MTCH2 and mitochondrial apoptosis pathway in mice, further study the relationship between the miRNA and MTCH2 and the MTCH2 role in mitochondrial apoptosis pathway of mouse spermatocytes via transfecting mimic and inhibitor of miR-450b-3p in vitro, so as to clarify the role of miRNA in the reproductive toxicity caused by SiNPs.…”

Section: Introductionmentioning

confidence: 99%

Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

Zhou

Liu

et al. 2020

Preprint

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Background: Silica nanoparticles (SiNPs) are found in environmental particulate matter and are proven to have adverse effects on fertility. The relationship and underlying mechanisms between miRNAs and apoptosis induced by SiNPs during spermatogenesis is currently ambiguous. Experimental design: The present study was designed to investigate the role of miRNA-450b-3p in the reproductive toxicity caused by SiNPs. In vivo, 40 male mice were randomly divided into control and SiNPs groups, 20 per group. The mice in the SiNPs group were administrated 20 mg/kg SiNPs by tracheal perfusion once every 5 days, for 35 days, and the control group were given the equivalent of a normal luminal saline. In vitro, spermatocyte cells were divided into 0 and 5 μg/mL SiNPs groups, after passaged for 30 generations, the GC-2spd cells in 5 μg/mL SiNPs groups were transfected with miRNA-450b-3p and its mimic and inhibitor. Results: In vivo, the results showed that SiNPs damaged tissue structures of testis, decreased the quantity and quality of the sperm, reduced the expression of miR-450b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, SiNPs obviously repressed the viability and increased the LDH level and apoptosis rate, decreased the levels of the miR-450b-3p, significantly enhanced the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3; while the mimic of miR-450b-3p reversed the changes induced by SiNPs, but inhibitor further promoted the effects induced by SiNPs.Conclusion: The result suggested that SiNPs could induce the spermatocyte apoptosis by inhibiting the miR-450b-3p expression to target promoting the MTCH2 resulting in activating mitochondrial apoptotic signaling pathways in the spermatocyte cells.

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MTCH2 is differentially expressed in rat testis and mainly related to apoptosis of spermatocytes

Cited by 10 publications

References 54 publications

Familial primary ovarian insufficiency associated with an SYCE1 point mutation: defective meiosis elucidated in humanized mice

Familial primary ovarian insufficiency associated with an SYCE1 point mutation: defective meiosis elucidated in humanized mice

Effect of transient scrotal hyperthermia on human sperm: an iTRAQ-based proteomic analysis

Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

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