Identification of a novel m.9588G &gt; A missense mutation in the mitochondrial COIII gene in asthenozoospermic Tunisian infertile men

Baklouti-Gargouri, Siwar; Ghorbel, Myriam; Mahmoud, Afif Ben; Mkaouar-Rebai, Emna; Cherif, Meriam; Chakroun, N.; Sellami, Afifa; Fakhfakh, Faiza; Keskes, Leila

doi:10.1007/s10815-014-0187-2

Cited by 24 publications

(18 citation statements)

References 20 publications

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“…Mitochondrial DNA (mtDNA) mutations/deletions might have several implications to male fertility 13313413536. The integrity and copy number of mtDNA were significantly correlated with sperm count and motility, as they were related to an increase of excessive ROS formation through increased lipid peroxidation in men presenting large-scale mtDNA deletions 135136137138139…”

Section: Main Factors Affecting Sperm Motilitymentioning

confidence: 99%

Major regulatory mechanisms involved in sperm motility

Pereira¹,

Sá²,

Barros³

et al. 2017

Asian J Androl

210

171

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The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.

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Section: Main Factors Affecting Sperm Motilitymentioning

confidence: 99%

Major regulatory mechanisms involved in sperm motility

Pereira¹,

Sá²,

Barros³

et al. 2017

Asian J Androl

210

171

View full text Add to dashboard Cite

show abstract

“…A number of proteins have been reported to be involved in mitochondrial dynamics during spermatogenesis, including the PTEN-induced putative kinase 1 (PINK1), Pld6 and Pa-pla 1 [ 1 , 4 , 8 , 16 , 22 ]. Male infertility has been linked to mitochondrial disorders such as hypospermatogenesis with abnormal lower mtHSP60 immunoreactivity and asthenozoospermia with mutation of the CO III gene [ 23 , 24 ]. Collectively, these studies demonstrate that tight regulation of mitochondrial function is essential for proper spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

et al. 2017

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Spermatids undergo the final steps of maturation during spermiogenesis, a process that necessitates extensive rearrangement of organelles such as the mitochondria. Male infertility has been linked to mitochondrial disorder, for example, hypospermatogenesis and asthenozoospermia. However, the mechanisms that regulate mitochondrial dynamics during spermiogenesis remain largely unknown. We found the glycerol kinase (Gyk)-like proteins glycerol kinase-like 1 (Gykl1) and glycerol kinase 2 (Gk2) were specifically localized to the mitochondria in spermatids. Male mice deficient in either Gykl1 or Gk2 were infertile due to dysfunctional spermatozoa, which exhibited unregulated ATP production, disordered mitochondrial sheath formation, abnormal mitochondrial morphology, and defective sperm tail. We demonstrated that the unique C-terminal sequences found in Gykl1 and Gk2 mediated their targeting to the mitochondrial outer membrane. Furthermore, both Gykl1 and Gk2 could interact with Pld6 (MitoPLD) and induce Pld6 and phosphatidic acid (PA)-dependent mitochondrial clustering in cells. Taken together, our study has revealed previously unsuspected functions of Gyk-like proteins in spermiogenesis, providing new insight into the potential mechanisms that lead to spermatozoa dysfunction and male infertility.

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“…Infertility affects 10-15% of the population, of which approximately 40% is due to male etiology and poor sperm quality characterized primarily as oligozoospermia, asthenozoospermia, and teratozoospermia [Baklouti-Gargouri et al 2013]. Numerous causes can lead to asthenozoospermia such as abnormal semen liquefaction, anti-sperm antibodies, varicocele, hormone disorders, physical and chemical factors, infections, and drug injury [Liu et al 2010].…”

Section: Introductionmentioning

confidence: 99%

The role of mitochondrial aconitate (ACO2) in human sperm motility

Tang

Liu

Wang

et al. 2014

Systems Biology in Reproductive Medicine

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Deficiencies in tricarboxylic acid (TCA) cycle enzymes have been shown to cause a wide spectrum of human diseases, including malignancies and neurological and cardiac diseases. In mammalian spermatozoa mitochondria, the TCA cycle is known to be a crucial metabolic pathway that contributes to produce ATP. There is little known about the role and mechanism of mitochondrial aconitase (ACO2), which is an important regulatory enzyme of the TCA cycle, in asthenozoospermia. In the current study, immunofluorescence staining localized ACO2 to the human sperm mid-piece. By immunoblotting, we demonstrated that the level of ACO2 protein in asthenozoospermic samples was significantly decreased compared with that in normal fertile men. Importantly, we first observed that co-incubation of isocitrate with low motile sperm suspensions significantly improved sperm motility, which might be due to elevated intracellular ATP. The improvement of the sperm motility by isocitrate may have important clinical implications in the treatment of asthenozoospermia and certainly warrants further investigation.

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Identification of a novel m.9588G > A missense mutation in the mitochondrial COIII gene in asthenozoospermic Tunisian infertile men

Cited by 24 publications

References 20 publications

Major regulatory mechanisms involved in sperm motility

Major regulatory mechanisms involved in sperm motility

Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility

The role of mitochondrial aconitate (ACO2) in human sperm motility

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