Human sperm motility: a molecular study of mitochondrial DNA, mitochondrial transcription factor A gene and DNA fragmentation

Faja, Fabiana; Carlini, Tania; Coltrinari, Giulia; Finocchi, Federica; Nespoli, Matteo; Pallotti, Francesco; Lenzi, Andrea; Lombardo, Francesco; Paoli, Donatella

doi:10.1007/s11033-019-04861-0

Cited by 26 publications

(43 citation statements)

References 51 publications

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“…Our results show that the level of transcript for Tfam decreases by β-ADRs-agonist-isoproterenol and β-ADRs-antagonist-propranolol abolish this effect. This is in line with findings that TFAM is associated with the reduction in mtDNA content of human sperm 34 and that TFAM gene expression positively correlate with abnormal forms, sperm DNA fragmentation and mtDNA copy number 35 , 36 . Our results showing that combination β-ADRs-antagonist-propranolol + β-ADRs-agonist-isoproterenol significantly decreased the level of Ucp2 suggest the positive involvement of β-ADRs in Ucp2 regulation and could be possible explanation for findings that UCP2 mitigates the loss of human spermatozoa motility 38 .…”

Section: Discussionsupporting

confidence: 91%

“…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 . It has been shown that TFAM is associated with the reduction in mtDNA content of human sperm 34 and that TFAM gene expression positive correlate with abnormal forms, sperm DNA fragmentation and mtDNA copy number 35 , 36 . Besides, mitophagy may be regulating human sperm function such as motility and viability 37 , UCP2 mitigates the loss of human spermatozoa motility 38 , while the expression level of MFN2 is related to motility and cryoprotective potentials of human sperm 39 .…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 91%

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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“…However, it has been shown that PPARGC1A and PRKAR1A are changed in spermatozoa of type 2 diabetes mellitus patients [ 55 ]. Furthermore, an increase in Nrf2 diminished testicular inflammation [ 56 ], while TFAM gene expression positively correlates with abnormal forms, sperm DNA fragmentation, and mtDNA copy number [ 29 , 30 ]. TFAM is essential for mammalian mtDNA transcription in animals and humans.…”

Section: Discussionmentioning

confidence: 99%

“…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 ]. Moreover, mitochondrial transcription factor TFAM (Transcription Factor A, Mitochondrial) causes the reduction of mtDNA content in human sperm [ 28 ], and the expression of TFAM gene positively correlates with abnormal forms, sperm DNA fragmentation, and mtDNA copy number [ 29 , 30 ]. Human sperm motility and viability are regulated by mitophagy [ 31 ].…”

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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“…Sperm mtDNA copy number (number of mtDNA copies per nuclear DNA copy) is also a sensitive biomarker of male fertility (Rajender, Rahul, & Mahdi, 2010). Human mtDNA copy number variations are associated with a decline of both sperm motility and fertility (Faja et al, 2019). An increase in mtDNA copy number along with a decrease in mtDNA integrity was observed in spermatozoa of infertile males with abnormal semen parameters (Song & Lewis, 2008).…”

Section: Impaired Sperm Motility and Dna Integritymentioning

confidence: 99%

Causes and consequences of sperm mitochondrial dysfunction

et al. 2020

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Mitochondria are multifunctional organelles found in most eukaryotic organisms. The mitochondrion forms a widespread network in many cells, which are dynamically regulated by a cascade of processes that are closely related albeit independent (Wu, Zhang, & Ren, 2019). The mitochondrion is referred to as the cell's powerhouse, as it supplies most of the cell's chemical energy in the form of adenine triphosphate (ATP). Besides generation of ATP, mitochondria play a key role in numerous basic and advanced cellular processes, including cellular homeostasis and apoptosis (Herst, Rowe, Carson, & Berridge, 2017). They are also essential for cellular signalling and communication through various means, including reactive oxygen species (ROS). The mitochondrial electron transport chain (ETC) induces the production of ROS required in signalling pathways, but if produced in excess, can cause oxidative damage (St John, Bowles, & Amaral, 2007). Although almost all of the cytoplasm is removed during spermatogenesis, mitochondria are retained in mature spermatozoa, which suggest its importance in male fertility (Zhang et al., 2019). Spermatozoa contain a limited number of mitochondria in the midpiece, which play a vital role in sperm function. The energy required for spermatozoa to carry out cellular processes necessary for successful fertilisation such as motility, hyperactivation,

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Human sperm motility: a molecular study of mitochondrial DNA, mitochondrial transcription factor A gene and DNA fragmentation

Cited by 26 publications

References 51 publications

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

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

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

Causes and consequences of sperm mitochondrial dysfunction

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