Altitude can alter the mtDNA copy number and nDNA integrity in sperm

Abstract

Objective Mitochondria are factories for energy production and genetic alterations in mtDNA will directly impact OXPHOS function. The copy number of mtDNA (i.e., the number of mtDNA per spermatozoon) is one of the major mitochondrial genetic features. Besides mtDNA copy number, the change of either mtDNA or nDNA integrity is another important factor causing asthenospermia, or poor sperm motility in infertile men. In this study, we investigated the mtDNA copy number and the integrities of mtDNA and nDNA respectively in semen samples from different donors at 5,300 m altitudes. Methods Total DNA was extracted from semen samples from donors in two different altitudes. Quantitative PCR was performed to evaluate the mtDNA copy number. PCR amplification was used to examine the integrity of sperm mtDNA. Flow cytometry was carried out to investigate sperm nDNA integrity. All data were analyzed to show the statistical significance. Results Sperm mtDNA copy number for those living at high altitude (5,300 m) for one month was significantly higher (P<0.05) than for those at the lower altitude (1,400 m) or in donors who had been living at the 5,300 m altitude for 1 year. In addition, sperm mtDNA copy numbers were remarkably decreased (P<0.05) in those who had lived at the greater altitude for 1 year compared to those who had lived there for one month. The ratio of nDNA integrity among the 10,000 sperms at high altitude for one month was significantly lower (P<0.05) than that at the lower altitude (1,400 m) or at 5,300 m for 1 year, and the ratio of nDNA integrity sperms at high altitude for 1 year was increased, and higher than that for at the lower altitude (P<0.05). Conclusion High altitude can alter the mtDNA copy number and nDNA integrity in the sperms.

Resistance of Sperm Motility to Serum Testosterone in Men with Excessive Erythrocytosis at High Altitude

“…Mitochondrial and nuclear DNAs are important for sperm motility. Sperm nuclear DNA integrity in donors living at 5 300 m for either 1 month or 1 year was signifi cantly less than in the control living at lower altitude [ 30 ] . Testosterone is an important contributor to the integrity of mitochondrial DNA [ 31 ] .…”

Analysis of mitochondrial DNA sequence and copy number variation across five high-altitude species and their low-altitude relatives

“…ROS (Luo et al 2011;McElroy and Chandel 2017). Moreover, we found the mtDNA copy number in highly aerobic brain (Larson et al 2014) and heart tissues (Nakada et al 2017) to exhibit higher copy number levels than in other tissues, meanwhile exhibiting a relatively greater change ratio of mtDNA copy number between low-and high-altitude animals across five species (Figure 2).…”

“…However, increase in mitochondrial density occur in the early phases of acclimatization in response to acute hypoxia, which increases the metabolic cost of oxygen at the expense of cell damage by harmful ROS (Luo et al. 2011 ; McElroy and Chandel 2017 ). Moreover, we found the mtDNA copy number in highly aerobic brain (Larson et al.…”

Alterations in telomere length and mitochondrial DNA copy number in human lymphocytes on short-term exposure to moderate hypoxia

“…While some studies have reported that TL and mtDNAcn are positively correlated in healthy individuals [ 47 , 65 ], others have reported that low lymphocyte mtDNAcn correlates with mitochondrion-related metabolic disorders [ [66] , [67] , [68] ]. Previous studies have reported conflicting results related to mtDNAcn in response to hypoxia; some studies reported an increase in mtDNAcn under hypoxic conditions [ [69] , [70] , [71] ], whereas others reported that, in some cell types, hypoxia could reduce mitochondrial biogenesis and mtDNA content [ [72] , [73] , [74] ]. Although in the current study, the correlations between TL and mtDNAcn under both moderate hypoxic conditions for 12 and 24 h showed negative trends, the correlations were not statistically significant.…”