Current Molecular Medicine

Author(s): Naina Kumar*

DOI: 10.2174/1566524022666220408104047

Sperm Mitochondria, the Driving Force Behind Human Spermatozoa Activities: Its Functions and Dysfunctions - A Narrative Review

Page: [332 - 340] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Male infertility is a major issue, and numerous factors contribute to it. One of the important organelles involved in the functioning of human spermatozoa is mitochondria. There are 50-75 mitochondria helically arranged in mid-piece bearing one mitochondrial DNA each. Sperm mitochondria play a crucial role in sperm functions, including the energy production required for sperm motility and the production of reactive oxygen species, which in the physiological range helps in sperm maturation, capacitation, and acrosome reaction. It also plays a role in calcium signaling cascades, intrinsic apoptosis, and sperm hyperactivation. Any structural or functional dysfunction of sperm mitochondria results in increased production of reactive oxygen species and, a state of oxidative stress, decreased energy production, all leading to sperm DNA damage, impaired sperm motility and semen parameters, and reduced male fertility. Furthermore, human sperm mitochondrial DNA mutations can result in impaired sperm motility and parameters leading to male infertility. Numerous types of point mutations, deletions, and missense mutations have been identified in mtDNA that are linked with male infertility.

Methods: Recent literature was searched from English language peer-reviewed journals from databases including PubMed, Scopus, EMBASE, Scholar, and Web of Science till September 2021. Search terms used were “Sperm mitochondria and male fertility”, “Bioenergetics of sperm”, “Sperm mitochondria and reactive oxygen species”, “Sperm mitochondrial mutations and infertility”.

Conclusion: Sperm mitochondria is an important organelle involved in various functions of human spermatozoa and sperm mitochondrial DNA has emerged as one of the potent biomarkers of sperm quality and male fertility.

Keywords: Adenosine Triphosphate, Male fertility, Mitochondria, Motility, Spermatozoa, Human Spermatozoa Activities.

[1]
Durairajanayagam D, Singh D, Agarwal A, Henkel R. Causes and consequences of sperm mitochondrial dysfunction. Andrologia 2021; 53(1): e13666.
[http://dx.doi.org/10.1111/and.13666] [PMID: 32510691]
[2]
Di Emidio G, Falone S, Artini PG, Amicarelli F, D’Alessandro AM, Tatone C. Mitochondrial sirtuins in reproduction. Antioxidants 2021; 10(7): 1047.
[http://dx.doi.org/10.3390/antiox10071047]
[3]
Darr CR, Cortopassi GA, Datta S, Varner DD, Meyers SA. Mitochondrial oxygen consumption is a unique indicator of stallion spermatozoal health and varies with cryopreservation media. Theriogenology 2016; 86(5): 1382-92.
[http://dx.doi.org/10.1016/j.theriogenology.2016.04.082] [PMID: 27242178]
[4]
Barbagallo F, La Vignera S, Cannarella R, Aversa A, Calogero AE, Condorelli RA. Evaluation of sperm mitochondrial function: A key organelle for sperm motility. J Clin Med 2020; 9(2): 363.
[http://dx.doi.org/10.3390/jcm9020363] [PMID: 32013061]
[5]
Moraes CR, Meyers S. The sperm mitochondrion: Organelle of many functions. Anim Reprod Sci 2018; 194: 71-80.
[http://dx.doi.org/10.1016/j.anireprosci.2018.03.024] [PMID: 29605167]
[6]
Rosati AJ, Whitcomb BW, Brandon N, et al. Sperm mitochondrial DNA biomarkers and couple fecundity. Hum Reprod 2020; 35(11): 2619-25.
[http://dx.doi.org/10.1093/humrep/deaa191] [PMID: 33021643]
[7]
Piomboni P, Focarelli R, Stendardi A, Ferramosca A, Zara V. The role of mitochondria in energy production for human sperm motility. Int J Androl 2012; 35(2): 109-24.
[http://dx.doi.org/10.1111/j.1365-2605.2011.01218.x] [PMID: 21950496]
[8]
Mortimer D. The functional anatomy of the human spermatozoon: Relating ultrastructure and function. Mol Hum Reprod 2018; 24(12): 567-92.
[http://dx.doi.org/10.1093/molehr/gay040] [PMID: 30215807]
[9]
Hirata S, Hoshi K, Shoda T, Mabuchi T. Spermatozoon and mitochondrial DNA. Reprod Med Biol 2002; 1(2): 41-7.
[http://dx.doi.org/10.1046/j.1445-5781.2002.00007.x] [PMID: 29699072]
[10]
May-Panloup P, Chrétien MF, Savagner F, et al. Increased sperm mitochondrial DNA content in male infertility. Hum Reprod 2003; 18(3): 550-6.
[http://dx.doi.org/10.1093/humrep/deg096] [PMID: 12615823]
[11]
Castellini C, D’Andrea S, Cordeschi G, et al. Pathophysiology of mitochondrial dysfunction in human spermatozoa: focus on energetic metabolism, oxidative stress and apoptosis. Antioxidants 2021; 10(5): 695.
[http://dx.doi.org/10.3390/antiox10050695] [PMID: 33924936]
[12]
Tao M, You CP, Zhao RR, et al. Animal mitochondria: Evolution, function, and disease. Curr Mol Med 2014; 14(1): 115-24.
[http://dx.doi.org/10.2174/15665240113136660081] [PMID: 24195633]
[13]
Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell 4th ed New York Garland Science. 2002.
[14]
van der Bliek AM, Sedensky MM, Morgan PG. Cell biology of the mitochondrion. Genetics 2017; 207(3): 843-71.
[http://dx.doi.org/10.1534/genetics.117.300262] [PMID: 29097398]
[15]
Park YJ, Pang MG. Mitochondrial functionality in male fertility: From spermatogenesis to fertilization. Antioxidants 2021; 10(1): 98.
[http://dx.doi.org/10.3390/antiox10010098] [PMID: 33445610]
[16]
Huang SG. Development of a high throughput screening assay for mitochondrial membrane potential in living cells. J Biomol Screen 2002; 7(4): 383-9.
[http://dx.doi.org/10.1177/108705710200700411] [PMID: 12230893]
[17]
Shrivastava N, Pande M. Mitochondrion: Features, functions and comparative analysis of specific probes in detecting sperm cell damages. Asian Pac J Reprod 2016; 5(6): 445-52.
[http://dx.doi.org/10.1016/j.apjr.2016.10.008]
[18]
Marchetti C, Obert G, Deffosez A, Formstecher P, Marchetti P. Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Hum Reprod 2002; 17(5): 1257-65.
[http://dx.doi.org/10.1093/humrep/17.5.1257] [PMID: 11980749]
[19]
Alamo A, De Luca C, Mongioì LM, et al. Mitochondrial membrane potential predicts 4-hour sperm motility. Biomedicines 2020; 8(7): 196.
[http://dx.doi.org/10.3390/biomedicines8070196] [PMID: 32645820]
[20]
Losano JDA, Padín JF, Méndez-López I, et al. The stimulated glycolytic pathway is able to maintain ATP levels and kinetic patterns of bovine epididymal sperm subjected to mitochondrial uncoupling. Oxid Med Cell Longev 2017; 2017: 1682393.
[http://dx.doi.org/10.1155/2017/1682393] [PMID: 28588746]
[21]
du Plessis SS, Agarwal A, Mohanty G, van der Linde M. Oxidative phosphorylation versus glycolysis: What fuel do spermatozoa use? Asian J Androl 2015; 17(2): 230-5.
[http://dx.doi.org/10.4103/1008-682X.135123] [PMID: 25475660]
[22]
Tourmente M, Villar-Moya P, Rial E, Roldan ER. Differences in ATP generation via glycolysis and oxidative phosphorylation and relationships with sperm motility in mouse species. J Biol Chem 2015; 290(33): 20613-26.
[http://dx.doi.org/10.1074/jbc.M115.664813] [PMID: 26048989]
[23]
Paoli D, Gallo M, Rizzo F, et al. Mitochondrial membrane potential profile and its correlation with increasing sperm motility. Fertil Steril 2011; 95(7): 2315-9.
[http://dx.doi.org/10.1016/j.fertnstert.2011.03.059] [PMID: 21507394]
[24]
Barbonetti A, Vassallo MR, Di Rosa A, et al. Involvement of mitochondrial dysfunction in the adverse effect exerted by seminal plasma from men with spinal cord injury on sperm motility. Andrology 2013; 1(3): 456-63.
[http://dx.doi.org/10.1111/j.2047-2927.2013.00077.x] [PMID: 23494980]
[25]
Chianese R, Pierantoni R. Mitochondrial reactive oxygen species (ROS) production alters sperm quality. Antioxidants 2021; 10(1): 92.
[http://dx.doi.org/10.3390/antiox10010092] [PMID: 33440836]
[26]
Orlando C, Krausz C, Forti G, Casano R. Simultaneous measurement of sperm LDH, LDH-X, CPK activities and ATP content in normospermic and oligozoospermic men. Int J Androl 1994; 17(1): 13-8.
[http://dx.doi.org/10.1111/j.1365-2605.1994.tb01202.x] [PMID: 8005703]
[27]
Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552(Pt 2): 335-44.
[http://dx.doi.org/10.1113/jphysiol.2003.049478] [PMID: 14561818]
[28]
Sabiha F. Role of Reactive Oxygen Species in Male Reproduction, Novel Prospects in Oxidative and Nitrosative Stress Pinar Atukeren, IntechOpen. 2018.Available from. https://www.intechopen.com/chapters/59757
[http://dx.doi.org/10.5772/intechopen.74763]
[29]
O’Flaherty C, de Lamirande E, Gagnon C. Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events. Free Radic Biol Med 2006; 41(4): 528-40.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.04.027] [PMID: 16863985]
[30]
Wagner H, Cheng JW, Ko EY. Role of reactive oxygen species in male infertility: An updated review of literature. Arab J Urol 2017; 16(1): 35-43.
[http://dx.doi.org/10.1016/j.aju.2017.11.001] [PMID: 29713534]
[31]
Durairajanayagam D. Physiological Role of Reactive Oxygen Species in Male Reproduction. Cambridge: Academic Press 2019; pp. 65-78.
[http://dx.doi.org/10.1016/B978-0-12-812501-4.00008-0]
[32]
Dutta S, Henkel R, Sengupta P, Agarwal A. Physiological role of ROS in sperm function Male Infertility Cham Springer. 2020.
[http://dx.doi.org/10.1007/978-3-030-32300-4_27]
[33]
D’Autréaux B, Toledano MB. ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 2007; 8(10): 813-24.
[http://dx.doi.org/10.1038/nrm2256] [PMID: 17848967]
[34]
Costello S, Michelangeli F, Nash K, et al. Ca2+-stores in sperm: Their identities and functions. Reproduction 2009; 138(3): 425-37.
[http://dx.doi.org/10.1530/REP-09-0134] [PMID: 19542252]
[35]
Mannowetz N, Naidoo NM, Choo SA, Smith JF, Lishko PV. Slo1 is the principal potassium channel of human spermatozoa. eLife 2013; 2: e01009.
[http://dx.doi.org/10.7554/eLife.01009] [PMID: 24137539]
[36]
Rahman MS, Kwon WS, Pang MG. Calcium influx and male fertility in the context of the sperm proteome: An update. BioMed Res Int 2014; 2014: 841615.
[http://dx.doi.org/10.1155/2014/841615] [PMID: 24877140]
[37]
Bravo A, Treulen F, Uribe P, Boguen R, Felmer R, Villegas JV. Effect of mitochondrial calcium uniporter blocking on human spermatozoa. Andrologia 2015; 47(6): 662-8.
[http://dx.doi.org/10.1111/and.12314] [PMID: 25059641]
[38]
Ardón F, Rodríguez-Miranda E, Beltrán C, Hernández-Cruz A, Darszon A. Mitochondrial inhibitors activate influx of external Ca2+ in sea urchin sperm. Biochim Biophys Acta 2009; 1787(1): 15-24.
[http://dx.doi.org/10.1016/j.bbabio.2008.10.003] [PMID: 19000650]
[39]
Breitbart H. Intracellular calcium regulation in sperm capacitation and acrosomal reaction. Mol Cell Endocrinol 2002; 187(1-2): 139-44.
[http://dx.doi.org/10.1016/S0303-7207(01)00704-3] [PMID: 11988321]
[40]
Losano JDA, Angrimani DSR, Ferreira Leite R, Simões da Silva BDC, Barnabe VH, Nichi M. Spermatic mitochondria: Role in oxidative homeostasis, sperm function and possible tools for their assessment. Zygote 2018; 26(4): 251-60.
[http://dx.doi.org/10.1017/S0967199418000242] [PMID: 30223916]
[41]
Jeong SY, Seol DW. The role of mitochondria in apoptosis. BMB Rep 2008; 41(1): 11-22.
[http://dx.doi.org/10.5483/BMBRep.2008.41.1.011] [PMID: 18304445]
[42]
Wang C, Youle RJ. The role of mitochondria in apoptosis. Annu Rev Genet 2009; 43: 95-118.
[http://dx.doi.org/10.1146/annurev-genet-102108-134850] [PMID: 19659442]
[43]
Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW. Three-dimensional structure of the apoptosome: Implications for assembly, procaspase-9 binding, and activation. Mol Cell 2002; 9(2): 423-32.
[http://dx.doi.org/10.1016/S1097-2765(02)00442-2] [PMID: 11864614]
[44]
Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 2006; 13(9): 1423-33.
[http://dx.doi.org/10.1038/sj.cdd.4401950] [PMID: 16676004]
[45]
Ricci G, Perticarari S, Fragonas E, et al. Apoptosis in human sperm: Its correlation with semen quality and the presence of leukocytes. Hum Reprod 2002; 17(10): 2665-72.
[http://dx.doi.org/10.1093/humrep/17.10.2665] [PMID: 12351546]
[46]
Aitken RJ, Baker MA. Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development. Int J Dev Biol 2013; 57(2-4): 265-72.
[http://dx.doi.org/10.1387/ijdb.130146ja] [PMID: 23784837]
[47]
Ferramosca A, Zara V. Bioenergetics of mammalian sperm capacitation. BioMed Res Int 2014; 2014: 902953.
[http://dx.doi.org/10.1155/2014/902953] [PMID: 24791005]
[48]
Puga Molina LC, Luque GM, Balestrini PA, Marín-Briggiler CI, Romarowski A, Buffone MG. Molecular basis of human sperm capacitation. Front Cell Dev Biol 2018; 6: 72.
[http://dx.doi.org/10.3389/fcell.2018.00072] [PMID: 30105226]
[49]
De Jonge C. Biological basis for human capacitation. Hum Reprod Update 2005; 11(3): 205-14.
[http://dx.doi.org/10.1093/humupd/dmi010] [PMID: 15817522]
[50]
Balbach M, Gervasi MG, Hidalgo DM, Visconti PE, Levin LR, Buck J. Metabolic changes in mouse sperm during capacitation†. Biol Reprod 2020; 103(4): 791-801.
[http://dx.doi.org/10.1093/biolre/ioaa114] [PMID: 32614044]
[51]
Balbach M, Buck J, Levin LR. Using an extracellular flux analyzer to measure changes in glycolysis and oxidative phosphorylation during mouse sperm capacitation. J Vis Exp 2020. (155)
[http://dx.doi.org/10.3791/60815] [PMID: 32065141]
[52]
Hidalgo DM, Romarowski A, Gervasi MG, et al. Capacitation increases glucose consumption in murine sperm. Mol Reprod Dev 2020; 87(10): 1037-47.
[http://dx.doi.org/10.1002/mrd.23421] [PMID: 32914502]
[53]
Carrageta DF, Guerra-Carvalho B, Sousa M, et al. Mitochondrial activation and reactive oxygen-species overproduction during sperm capacitation are independent of glucose stimuli. Antioxidants 2020; 9(8): 750.
[http://dx.doi.org/10.3390/antiox9080750] [PMID: 32823893]
[54]
Stendardi A, Focarelli R, Piomboni P, et al. Evaluation of mitochondrial respiratory efficiency during in vitro capacitation of human spermatozoa. Int J Androl 2011; 34(3): 247-55.
[http://dx.doi.org/10.1111/j.1365-2605.2010.01078.x] [PMID: 20546047]
[55]
Crozet N. Acrosome reaction and fertilization. Contracept Fertil Sex 1994; 22(5): 328-30.
[56]
Zhang G, Yang W, Zou P, et al. Mitochondrial functionality modifies human sperm acrosin activity, acrosome reaction capability and chromatin integrity. Hum Reprod 2019; 34(1): 3-11.
[http://dx.doi.org/10.1093/humrep/dey335] [PMID: 30428044]
[57]
Mao HT, Yang WX. Modes of acrosin functioning during fertilization. Gene 2013; 526(2): 75-9.
[http://dx.doi.org/10.1016/j.gene.2013.05.058] [PMID: 23747402]
[58]
Ramió-Lluch L, Fernández-Novell JM, Peña A, et al. ‘In vitro’ capacitation and acrosome reaction are concomitant with specific changes in mitochondrial activity in boar sperm: Evidence for a nucleated mitochondrial activation and for the existence of a capacitation-sensitive subpopulational structure. Reprod Domest Anim 2011; 46(4): 664-73.
[http://dx.doi.org/10.1111/j.1439-0531.2010.01725.x] [PMID: 21121968]
[59]
Ruiz-Pesini E, Díez-Sánchez C, López-Pérez MJ, Enríquez JA. The role of the mitochondrion in sperm function: Is there a place for oxidative phosphorylation or is this a purely glycolytic process? Curr Top Dev Biol 2007; 77: 3-19.
[http://dx.doi.org/10.1016/S0070-2153(06)77001-6] [PMID: 17222698]
[60]
Darr CR, Varner DD, Teague S, Cortopassi GA, Datta S, Meyers SA. Lactate and pyruvate are major sources of energy for stallion sperm with dose effects on mitochondrial function, motility, and ROS production. Biol Reprod 2016; 95(2): 34.
[http://dx.doi.org/10.1095/biolreprod.116.140707] [PMID: 27335066]
[61]
Nowicka-Bauer K, Lepczynski A, Ozgo M, et al. Sperm mitochondrial dysfunction and oxidative stress as possible reasons for isolated asthenozoospermia. J Physiol Pharmacol 2018; 69(3)
[http://dx.doi.org/10.26402/jpp.2018.3.05] [PMID: 30149371]
[62]
Zorova LD, Popkov VA, Plotnikov EY, et al. Mitochondrial membrane potential. Anal Biochem 2018; 552: 50-9.
[http://dx.doi.org/10.1016/j.ab.2017.07.009] [PMID: 28711444]
[63]
Zhang WD, Zhang Z, Jia LT, et al. Oxygen free radicals and mitochondrial signaling in oligospermia and asthenospermia. Mol Med Rep 2014; 10(4): 1875-80.
[http://dx.doi.org/10.3892/mmr.2014.2428] [PMID: 25109708]
[64]
Pelliccione F, Micillo A, Cordeschi G, et al. Altered ultrastructure of mitochondrial membranes is strongly associated with unexplained asthenozoospermia. Fertil Steril 2011; 95(2): 641-6.
[http://dx.doi.org/10.1016/j.fertnstert.2010.07.1086] [PMID: 20840880]
[65]
Pelliccione F, Verratti V, D’Angeli A, et al. Physical exercise at high altitude is associated with a testicular dysfunction leading to reduced sperm concentration but healthy sperm quality. Fertil Steril 2011; 96(1): 28-33.
[http://dx.doi.org/10.1016/j.fertnstert.2011.03.111] [PMID: 21561607]
[66]
Chen Y, Cai GH, Xia B, et al. Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production. FASEB J 2020; 34(5): 6688-702.
[http://dx.doi.org/10.1096/fj.201903224RR] [PMID: 32212192]
[67]
Tang M, Liu BJ, Wang SQ, et al. The role of mitochondrial aconitate (ACO2) in human sperm motility. Syst Biol Reprod Med 2014; 60(5): 251-6.
[http://dx.doi.org/10.3109/19396368.2014.915360] [PMID: 24785945]
[68]
Piasecka M, Kawiak J. Sperm mitochondria of patients with normal sperm motility and with asthenozoospermia: Morphological and functional study. Folia Histochem Cytobiol 2003; 41(3): 125-39.
[PMID: 13678331]
[69]
Yao L, Zhao D, Yu H, et al. Oxidative stress-related mitochondrial dysfunction as a possible reason for obese male infertility. Nutr Clin Metab 2021; 35(2): 123-8.
[http://dx.doi.org/10.1016/j.nupar.2020.02.438]
[70]
Schuppe HC, Meinhardt A, Allam JP, Bergmann M, Weidner W, Haidl G. Chronic orchitis: A neglected cause of male infertility? Andrologia 2008; 40(2): 84-91.
[http://dx.doi.org/10.1111/j.1439-0272.2008.00837.x] [PMID: 18336456]
[71]
Tremellen K. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update 2008; 14(3): 243-58.
[http://dx.doi.org/10.1093/humupd/dmn004] [PMID: 18281241]
[72]
Ford WC. Regulation of sperm function by reactive oxygen species. Hum Reprod Update 2004; 10(5): 387-99.
[http://dx.doi.org/10.1093/humupd/dmh034] [PMID: 15218008]
[73]
Agarwal A, Said TM. Oxidative stress, DNA damage and apoptosis in male infertility: A clinical approach. BJU Int 2005; 95(4): 503-7.
[http://dx.doi.org/10.1111/j.1464-410X.2005.05328.x] [PMID: 15705068]
[74]
Kumar DP, Sangeetha N. Mitochondrial DNA mutations and male infertility. Indian J Hum Genet 2009; 15(3): 93-7.
[http://dx.doi.org/10.4103/0971-6866.60183] [PMID: 21088712]
[75]
Dzudzor B, Bimah B, Amarh V, Ocloo A. Sperm parameters and mitochondrial DNA sequence variants among patients at a fertility clinic in Ghana. PLoS One 2021; 16(6): e0252923.
[http://dx.doi.org/10.1371/journal.pone.0252923] [PMID: 34129647]
[76]
Talebi E, Karimian M, Nikzad H. Association of sperm mitochondrial DNA deletions with male infertility in an Iranian population. Mitochondrial DNA A DNA Mapp Seq Anal 2018; 29(4): 615-23.
[http://dx.doi.org/10.1080/24701394.2017.1331347] [PMID: 28537774]
[77]
Zoubi MSA, Al-Talafha AM, Sharu EA, et al. Correlation of sperm mitochondrial DNA 7345 bp and 7599 bp deletions with asthenozoospermia in jordanian population. J Reprod Infertil 2021; 22(3): 165-72.
[http://dx.doi.org/10.18502/jri.v22i3.6717] [PMID: 34900637]
[78]
Holyoake AJ, McHugh P, Wu M, et al. High incidence of single nucleotide substitutions in the mitochondrial genome is associated with poor semen parameters in men. Int J Androl 2001; 24(3): 175-82.
[http://dx.doi.org/10.1046/j.1365-2605.2001.00292.x] [PMID: 11380706]
[79]
Zhang G, Wang Z, Ling X, et al. Mitochondrial biomarkers reflect semen quality: Results from the marchs study in chongqing, China. PLoS One 2016; 11(12): e0168823.
[http://dx.doi.org/10.1371/journal.pone.0168823] [PMID: 28006017]
[80]
Vertika S, Singh KK, Rajender S. Mitochondria, spermato-genesis, and male infertility - An update. Mitochondrion 2020; 54: 26-40.
[http://dx.doi.org/10.1016/j.mito.2020.06.003] [PMID: 32534048]
[81]
Pal A, Ambulkar P, Sontakke B, Waghmare J, Shende M, Tarnekar A. Nucleus 2017; 60: 209-20.
[http://dx.doi.org/10.1007/s13237-017-0209-4]
[82]
Shamsi MB, Kumar R, Bhatt A, et al. Mitochondrial DNA Mutations in etiopathogenesis of male infertility. Indian J Urol 2008; 24(2): 150-4.
[http://dx.doi.org/10.4103/0970-1591.40606] [PMID: 19468388]
[83]
Shamsi MB, Kumar K, Dada R. Genetic and epigenetic factors: Role in male infertility. Indian J Urol 2011; 27(1): 110-20.
[http://dx.doi.org/10.4103/0970-1591.78436] [PMID: 21716934]
[84]
Varghese AC, du Plessis SS, Agarwal A. Male gamete survival at stake: Causes and solutions. Reprod Biomed Online 2008; 17(6): 866-80.
[http://dx.doi.org/10.1016/S1472-6483(10)60416-6] [PMID: 19079972]
[85]
Tahmasbpour E, Balasubramanian D, Agarwal A. A multi-faceted approach to understanding male infertility: Gene mutations, molecular defects and assisted reproductive techniques (ART). J Assist Reprod Genet 2014; 31(9): 1115-37.
[http://dx.doi.org/10.1007/s10815-014-0280-6] [PMID: 25117645]