Comparison of large‐scale deletions of the sperm mitochondrial DNA in normozoospermic and asthenoteratozoospermic men

Gholinezhad, Maryam; Yousefnia-Pasha, Yousefreza; Colagar, Abasalt Hosseinzadeh; Mohammadoo‐Khorasani, Milad; Bidmeshkipour, Ali

doi:10.1002/jcb.27492

Cited by 14 publications

(12 citation statements)

References 36 publications

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“…Defects of mtDNA in oligoasthenozoospermic patients made DNA unavailable for amplification [ 22 ]. Large-scale deletions of mtDNA were pointed to as risk factors for poor sperm quality in asthenoteratozoospermia-induced male infertility [ 23 ]. Beside mtDNA, the importance of mitochondrial membrane potential is recognized not only for spermatozoa functionality [ 24 , 25 , 26 ], but also, in combination with sperm DNA fragmentation, as standard semen parameter for the prediction of natural conception [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Starovlah

Pletikosic

Kostic

et al. 2021

IJMS

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Here, we study possible mechanisms of (in/sub)fertility related to the acute or repeated psychological stresses (the most common stresses in human society) by following the transcriptional profile of 22 mitochondrial dynamics/function markers and 22 signaling molecules regulating both mitochondrial dynamics and spermatozoa number/functionality. An in vivo study mimicking acute (once for 3 h) and repeated (3 h for 10 consecutive days) psychophysical stress was performed on adult rats. The analysis of hormones, the number/functionality of spermatozoa, and 44 transcriptional markers were performed on individual samples from up to 12 animals per group. Results showed that both types of stress reduced spermatozoa functionality (acute by 4.4-fold, repeated by 3.3-fold) and ATP production (acute by 2.3-fold, repeated by 14.5-fold), while only repeated stress reduces the number of spermatozoa (1.9-fold). Stress significantly disturbed transcription of 34-out-of-44 markers (77%). Mitochondrial dynamics and functionality markers: 18-out-of-22 =>82% (mitochondrial-biogenesis-markers –>6-out-of-8 =>75%; mitochondrial-fusion-markers –>3-out-of-3 =>100%; mitochondrial-fission-markers –>1-out-of-2 =>50%; mitochondrial-autophagy-markers –>3-out-of-3 =>100%; mitochondrial-functionality-markers –>5-out-of-6 =>83%). Markers of signaling pathways regulating both mitochondrial dynamics/functionality and spermatozoa number/functionality important for male (in/sub)fertility –>16-out-of-22 =>73% (cAMP-signaling-markers –>8-out-of-12 =>67%; MAPK-signaling-markers –>8-out-of-10 =>80%). Accordingly, stress-triggered changes of transcriptional profile of mitochondrial dynamics/functionality markers as well as signaling molecules regulating both mitochondrial dynamics and spermatozoa number and functionality represent adaptive mechanisms.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Starovlah

Pletikosic

Kostic

et al. 2021

IJMS

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“…The mitochondrial morphological changes are specific for stages of spermatogenesis 26 and could explain the strong association of altered ultrastructure of mitochondria with unexplained asthenozoospermia 27 . Clinical trials showed that the mtDNA of oligo-asthenozoospermic patients present some defects that made DNA unavailable for amplification 28 and that large-scale deletions of mtDNA may be genetic risk factors for poor sperm quality in asthenoteratozoospermia-induced male infertility 29 . Numerous studies on humans pointed the importance of mitochondrial membrane potential not only for spermatozoa functionality 30 – 32 but also, in combination with sperm DNA fragmentation, as a superior to standard semen parameters for the prediction of natural conception 33 .…”

Section: Introductionmentioning

confidence: 99%

Reduced spermatozoa functionality during stress is the consequence of adrenergic-mediated disturbance of mitochondrial dynamics markers

Starovlah

Pletikosic

Kostic

et al. 2020

Sci Rep

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Here we investigate the stress-signaling responsible for the effects of acute/repeated psychological stresses (the most common stresses in human society) on spermatozoa number and functionality, as well as the transcriptional profile of mitochondrial dynamics markers by using the in vivo and ex vivo approaches. Acute and repeated stress inhibit spermatozoa functionality (acute –> 3.2-fold, repeated –> 2.5-fold), while only repeated stress reduces the spermatozoa number (1.7-fold). Stress hormones mimic these effects and decrease the spermatozoa functionality (adrenaline: 10 µM –> 2.4-fold, 100 µM – > 2.8-fold; hydrocortisone: 50 pM –> 2.7-fold, 500 pM –> 8.5-fold). They also significantly disturb the transcriptional profile of all main mitochondrial dynamics markers in spermatozoa. Ex vivo manipulation of stress signaling in spermatozoa reveals that most of these effects are mediated through ɑ1-and/or-β-adrenergic receptors. The transcription of these receptors and their kinases in the same samples is under the significant influence of adrenergic signaling. Our results are the first to show the importance of mitochondrial dynamics markers in spermatozoa since the transcriptional profiles of sixteen-out-of-ninteen are disturbed by manipulation of stress-hormones-signaling. This is a completely new molecular approach to assess spermatozoa functionality and it is important for a better understanding of the correlations between stress, environmental-life-style and other factors, and male (in)fertility.

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“…For instance, 4,977 and 7,599 bp deletions of mtDNA have been related to male infertility in different populations (Kumar & Sangeetha, 2009; Talebi et al., 2018). Other large‐scale mutations such as 7436‐bp and 4866‐bp deletion have been described to be related to the possible association with male infertility (Chari et al., 2015; Gholinezhad et al., 2019; Karimian & Babaei, 2020). Therefore, the complete portrait of the molecular markers related to male infertility needs to be developed by screening the high‐risk variants in different populations to elucidate the most common genetic mutations and variations that are related to the development of male infertility.…”

Section: Discussionmentioning

confidence: 99%

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT‐ND3andMT‐ND4L) and male infertility

et al. 2021

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Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT‐ND3 and MT‐ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT‐ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT‐ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT‐ND3 and MT‐ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT‐ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT‐ND3 and MT‐ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.

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Comparison of large‐scale deletions of the sperm mitochondrial DNA in normozoospermic and asthenoteratozoospermic men

Abstract: Our findings suggested that these large-scale deletions of mtDNA may be genetic risk factors for poor sperm quality in asthenoteratozoospermia-induced male infertility. Thus, it is necessary to understand the mechanisms behind the generation of these deletions.

Cited by 14 publications

References 36 publications

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Mitochondrial Dynamics Markers and Related Signaling Molecules Are Important Regulators of Spermatozoa Number and Functionality

Reduced spermatozoa functionality during stress is the consequence of adrenergic-mediated disturbance of mitochondrial dynamics markers

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT‐ND3andMT‐ND4L) and male infertility

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