Deletion of murine choline dehydrogenase results in diminished sperm motility

Johnson, Amy; Craciunescu, Corneliu N.; Guo, Zhong; Teng, Ya Wen; Thresher, Randy J.; Blusztajn, Jan Krzysztof; Zeisel, Steven H.

doi:10.1096/fj.09-153718

Cited by 63 publications

(72 citation statements)

References 59 publications

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“…Finally, knockout of the choline dehydrogenase gene (Chdh) in mice has been shown to decrease sperm motility [68]. Similarly, polymorphism in the human Chdh gene also is associated with variation in sperm motility [69].…”

Section: (D) Possible Functions Of Cg9509mentioning

confidence: 99%

Adaptive divergence of a transcriptional enhancer between populations ofDrosophila melanogaster

Glaser-Schmitt¹,

Catalán²,

Parsch³

2013

Phil. Trans. R. Soc. B

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ResearchAs species colonize new habitats they must adapt to the local environment. Much of this adaptation is thought to occur at the regulatory level; however, the relationships among genetic polymorphism, expression variation and adaptation are poorly understood. Drosophila melanogaster, which expanded from an ancestral range in sub-Saharan Africa around 15 000 years ago, represents an excellent model system for studying regulatory evolution. Here, we focus on the gene CG9509, which differs in expression between an African and a European population of D. melanogaster. The expression difference is caused by variation within a transcriptional enhancer adjacent to the CG9509 coding sequence. Patterns of sequence variation indicate that this enhancer was the target of recent positive selection, suggesting that the expression difference is adaptive. Analysis of the CG9509 enhancer in new population samples from Europe, Asia, northern Africa and subSaharan Africa revealed that sequence polymorphism is greatly reduced outside the ancestral range. A derived haplotype absent in sub-Saharan Africa is at high frequency in all other populations. These observations are consistent with a selective sweep accompanying the range expansion of the species. The new data help identify the sequence changes responsible for the difference in enhancer activity.

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Section: (D) Possible Functions Of Cg9509mentioning

confidence: 99%

Adaptive divergence of a transcriptional enhancer between populations ofDrosophila melanogaster

Glaser-Schmitt¹,

Catalán²,

Parsch³

2013

Phil. Trans. R. Soc. B

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“…The purity of the mitochondrial fraction obtained was evaluated by assaying the succinate dehydrogenase enzyme activity according to the method of Johnson et al (21). For this assay, we used 4.5 g of proteins from the premitochondrial pellet, mitochondrion-enriched fraction, and postmitochondrial supernatant.…”

Section: Methodsmentioning

confidence: 99%

Leishmania major Telomerase TERT Protein Has a Nuclear/Mitochondrial Eclipsed Distribution That Is Affected by Oxidative Stress

et al. 2015

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In its canonical role the reverse transcriptase telomerase recovers the telomeric repeats that are lost during DNA replication. Other locations and activities have been recently described for the telomerase protein subunit TERT in mammalian cells. In the present work, using biochemistry, molecular biology, and electron microscopy techniques, we found that in the human parasite Leishmania major, TERT (and telomerase activity) shared locations between the nuclear, mitochondrial, and cytoplasmic compartments. Also, some telomerase activity and TERT protein could be found in ϳ100-nm nanovesicles. In the mitochondrial compartment, TERT appears to be mainly associated with the kinetoplast DNA. When Leishmania cells were exposed to H 2 O 2 , TERT changed its relative abundance and activity between the nuclear and mitochondrial compartments, with the majority of activity residing in the mitochondrion. Finally, overexpression of TERT in Leishmania transfected cells not only increased the parasitic cell growth rate but also increased their resistance to oxidative stress. Mammalian telomeres are nucleoprotein complexes with double and single DNA strand (telomeric overhang) runs of TTAGGG repeats, a chromatin organization containing methylated H3 and H4 histones, and a heavily methylated DNA, which are features of a transcriptionally repressed zone. At the ends of linear chromosomes, since DNA polymerases do not initiate DNA synthesis de novo, the new DNA synthesized over the lagging strand lacks the primer for the completion of its synthesis, leaving a gap; how to seal this gap has been named the end replication problem (1). Most eukaryotes solve the problem using mechanisms in which the enzyme telomerase plays an important role (2). Telomerase has been described for most eukaryotic cells, and in fact, the first report of telomerase was made for the protozoan Tetrahymena (2). The telomerase core has two components: a reverse transcriptase (TERT) protein and an RNA subunit (TER) that provides the template for copying the hexameric repeats to the telomeric overhang (2). In addition, mammalian telomeres contain a six-protein complex called shelterin that regulates the telomerase activity and protects the chromosomal ends from nucleolytic degradation and chromosomal rearrangements (3).The TERT component has the typical motifs of reverse transcriptase enzymes (1, 2, A, B=, C, and E) and a telomerase-specific T-domain (4), whereas the TER subunit has been sequenced in a large number of organisms, and the length of the RNA varies from ϳ200 to 1,300 nucleotides (nt) (5).Growing evidence indicates that TERT plays multiple roles in addition to its telomeric function, including (i) acting as a transcriptional modulator of the ␤-catenin signaling pathway in mice; (ii) interacting with an RNA component of mitochondrial RNA processing endoribonuclease (RMRP), creating a new activity that synthetizes RNA in a RNA-dependent manner and generating a double-stranded RNA (dsRNA) that enters into the RNA interference (RNAi) cascade; (iii) regu...

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“…This finding suggests that betaine plays a critical role in testicular function. 18 Furthermore, testis, liver and kidney tissues have the highest CHDH activity, and choline and betaine concentrations are the most altered by CHDH gene deletion at these sites. 18 The significance of the CHDH gene in the male reproductive system has been confirmed by studies of CHDH knockout male mice.…”

Section: Introductionmentioning

confidence: 99%

“…18 Furthermore, testis, liver and kidney tissues have the highest CHDH activity, and choline and betaine concentrations are the most altered by CHDH gene deletion at these sites. 18 The significance of the CHDH gene in the male reproductive system has been confirmed by studies of CHDH knockout male mice. The impaired fertility of these mice is mainly due to diminished sperm motility, abnormal mitochondrial morphology, inner membrane polarisation and reduced ATP content.…”

Section: Introductionmentioning

confidence: 99%

“…The impaired fertility of these mice is mainly due to diminished sperm motility, abnormal mitochondrial morphology, inner membrane polarisation and reduced ATP content. 18 In humans, a great amount of variation in the PEMT and CHDH genes has been identified. Of the variants, PEMT rs12325817 (1744GRC) and CHDH rs12676 (2432GRT) have been found to affect PEMT and CHDH gene activity, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Phosphatidylethanolamine N-methyltransferase and choline dehydrogenase gene polymorphisms are associated with human sperm concentration

Lazaros

Xita²,

Hatzi³

et al. 2012

Asian J Androl

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Choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N-methyltransferase (PEMT) and choline dehydrogenase (CHDH), two basic enzymes of choline metabolism, have been observed in the human testis, demonstrating their gene expression in this tissue. In the present study, we explored the contribution of the PEMT and CHDH gene variants to sperm parameters. Two hundred oligospermic and 250 normozoospermic men were recruited. DNA was extracted from the spermatozoa, and the PEMT 2774G.C and CHDH 1432G.T polymorphisms were genotyped. The genotype distribution of the PEMT 2774G.C polymorphism did not differ between oligospermic and normozoospermic men. In contrast, in the case of the CHDH 1432G.T polymorphism, oligospermic men presented the CHDH 432G/G genotype more frequently than normozoospermic men (62% vs. 42%, P,0.001). The PEMT 774G/G genotype was associated with a higher sperm concentration compared to the PEMT 774G/C and 774C/C genotypes in oligospermic men (12.565.6310 6 spermatozoa ml 21 vs. 8.365.2310 6 spermatozoa ml 21 , P,0.002) and normozoospermic men (81.5655.6310 6 vs. 68.1644.5310 6 spermatozoa ml 21 , P,0.006). In addition, the CHDH 432G/G genotype was associated with higher sperm concentration compared to CHDH 432G/T and 432T/T genotypes in oligospermic (11.865.1310 6 vs. 7.865.3310 6 spermatozoa ml 21 , P,0.003) and normozoospermic men (98.6662.2310 6 vs. 58.8633.6310 6 spermatozoa ml 21 , P,0.001). In our series, the PEMT 2774G.C and CHDH 1432G.T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality.

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Deletion of murine choline dehydrogenase results in diminished sperm motility

Cited by 63 publications

References 59 publications

Adaptive divergence of a transcriptional enhancer between populations ofDrosophila melanogaster

Adaptive divergence of a transcriptional enhancer between populations ofDrosophila melanogaster

Leishmania major Telomerase TERT Protein Has a Nuclear/Mitochondrial Eclipsed Distribution That Is Affected by Oxidative Stress

Phosphatidylethanolamine N-methyltransferase and choline dehydrogenase gene polymorphisms are associated with human sperm concentration

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