medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.12.45-51medgen-2386Research ArticleНАУЧНЫЙ ОБЗОРREVIEWКопийность митохондриальной ДНК в сперматозоидах и мужская фертильностьSperm mitochondrial DNA copy number and male fertilityХаятС. Ш.KhayatS. Sh.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

КурилоЛ. Ф.KuriloL. F.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

ЧерныхВ. Б.ChernykhV. B.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechie st., Moscow, 115478

ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian Federation20232312202322124551Copyright © Хаят С.Ш., Курило Л.Ф., Черных В.Б., 20232023Хаят С.Ш., Курило Л.Ф., Черных В.Б.Khayat S.S., Kurilo L.F., Chernykh V.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2386

В настоящее время изучение митохондриального генома в мужских и женских половых клетках является одной из активно исследуемых областей в репродуктивной генетике. Ряд авторов свидетельствует о наличии связи между копийностью мтДНК, качеством гамет и фертильностным потенциалом. Мужская фертильность в значительной мере зависит от параметров семенной жидкости, в частности, от количества и качества сперматозоидов, на которые влияет множество генетических и негенетических факторов. Одними из факторов снижения подвижности сперматозоидов являются нарушение функции митохондрий, изменения митохондриальной ДНК (мтДНК) в мужских половых клетках. В данной статье представлен краткий обзор исследований, связанных с содержанием митохондриальной ДНК в сперматозоидах в норме и при различных формах патозооспермии.

Currently, the study of mitochondrial genome in male and female gametes is one of the actively investigated topics in reproductive genetics. A number of authors argue that there is an association between mtDNA copy number, quality of gametes, and fertility potential. Male fertility depends on a large extent on seminal fluid parameters, in particular on the quantity and quality of spermatozoa, which are influenced by many genetic and non-genetic factors. Some of the genetic factors of decreased sperm motility are mitochondrial dysfunction, mitochondrial DNA (mtDNA) abnormalities in male germ cells. This article presents a brief review of the results of studies related to the mitochondrial DNA content in normal sperm parameters and various forms of pathozoospermia.

митохондриимитохондриальная ДНК (мтДНК)сперматогенезполовые клеткифертильностьпатозооспермияmitochondriamitochondrial DNA (mtDNA)spermatogenesisgerm cellsfertilitypathozoospermiaReferencesdu Plessis S.S., 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. doi: 10.4103/1008-682X.135123.du Plessis S.S., 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. doi: 10.4103/1008-682X.135123.Даниленко Н.Г., Давыденко О.Г. Миры геномов органелл. Минск: Технология, 2003. 494 с.Даниленко Н.Г., Давыденко О.Г. Миры геномов органелл. Минск: Технология, 2003. 494 с.Yan C., Duanmu X., Zeng L., et al. Mitochondrial DNA: Distribution, Mutations, and Elimination. Cells. 2019;8(4):379. doi: 10.3390/cells8040379Yan C., Duanmu X., Zeng L., et al. Mitochondrial DNA: Distribution, Mutations, and Elimination. Cells. 2019;8(4):379. doi: 10.3390/cells8040379Wai T., Ao A., Zhang X., et al. The role of mitochondrial DNA copy number in mammalian fertility. Biol Reprod 2010; 83:52–62.Wai T., Ao A., Zhang X., et al. The role of mitochondrial DNA copy number in mammalian fertility. Biol Reprod 2010; 83:52–62.Faja F., Carlini T., Coltrinari G., et al. Human sperm motility: a molecular study of mitochondrial DNA, mitochondrial transcription factor A gene and DNA fragmentation. Mol Biol Rep. 2019;46(4):4113-4121.Faja F., Carlini T., Coltrinari G., et al. Human sperm motility: a molecular study of mitochondrial DNA, mitochondrial transcription factor A gene and DNA fragmentation. Mol Biol Rep. 2019;46(4):4113-4121.Chabi B., Mousson de Camaret B., Duborjal H., et al. Quantification of mitochondrial DNA deletion, depletion, and overreplication: application to diagnosis. Clin Chem. 2003;49(8):1309-17. doi: 10.1373/49.8.1309.Chabi B., Mousson de Camaret B., Duborjal H., et al. Quantification of mitochondrial DNA deletion, depletion, and overreplication: application to diagnosis. Clin Chem. 2003;49(8):1309-17. doi: 10.1373/49.8.1309.Kelly R.D., Mahmud A., McKenzie M., et al. Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A. Nucleic Acids Res. 2012;40(20):10124-38. doi: 10.1093/nar/gks770.Kelly R.D., Mahmud A., McKenzie M., et al. Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A. Nucleic Acids Res. 2012;40(20):10124-38. doi: 10.1093/nar/gks770.Miller F.J., Rosenfeldt F.L., Zhang C., et al. Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. Nucleic Acids Res. 2003;31(11):e61. doi: 10.1093/nar/gng060.Miller F.J., Rosenfeldt F.L., Zhang C., et al. Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. Nucleic Acids Res. 2003;31(11):e61. doi: 10.1093/nar/gng060.Castellani C.A., Longchamps R.J., Sun J., et al. Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease. Mitochondrion. 2020;53:214-223. doi: 10.1016/j.mito.2020.06.004.Castellani C.A., Longchamps R.J., Sun J., et al. Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease. Mitochondrion. 2020;53:214-223. doi: 10.1016/j.mito.2020.06.004.Chen X., Prosser R., Simonetti S., et al. Rearranged mitochondrial genomes are present in human oocytes. Am J Hum Genet. 1995;57(2):239-47.Chen X., Prosser R., Simonetti S., et al. Rearranged mitochondrial genomes are present in human oocytes. Am J Hum Genet. 1995;57(2):239-47.Ankel-Simons F., Cummins J.M. Misconceptions about mitochondria and mammalian fertilization: implications for theories on human evolution. Proc Natl AcadSci U S A. 1996;93(24):13859-63. doi: 10.1073/pnas.93.24.13859Ankel-Simons F., Cummins J.M. Misconceptions about mitochondria and mammalian fertilization: implications for theories on human evolution. Proc Natl AcadSci U S A. 1996;93(24):13859-63. doi: 10.1073/pnas.93.24.13859Díez-Sánchez C., Ruiz-Pesini E., Lapeña A.C., et al. Mitochondrial DNA content of human spermatozoa. Biol Reprod. 2003;68(1):1805. doi: 10.1095/biolreprod.102.005140Díez-Sánchez C., Ruiz-Pesini E., Lapeña A.C., et al. Mitochondrial DNA content of human spermatozoa. Biol Reprod. 2003;68(1):1805. doi: 10.1095/biolreprod.102.005140Yu M. Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers. Life Sci. 2011;89(34):65-71. doi: 10.1016/j.lfs.2011.05.010.Yu M. Generation, function and diagnostic value of mitochondrial DNA copy number alterations in human cancers. Life Sci. 2011;89(34):65-71. doi: 10.1016/j.lfs.2011.05.010.Clay Montier L.L., Deng J.J., Bai Y. Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genomics. 2009;36(3):125-31. doi: 10.1016/S1673-8527(08)60099-5.Clay Montier L.L., Deng J.J., Bai Y. Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genomics. 2009;36(3):125-31. doi: 10.1016/S1673-8527(08)60099-5.Malik A.N., Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction? Mitochondrion. 2013;13(5):481-92. doi: 10.1016/j.mito.2012.10.011.].Malik A.N., Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction? Mitochondrion. 2013;13(5):481-92. doi: 10.1016/j.mito.2012.10.011.].Carra E., Sangiorgi D., Gattuccio F., Rinaldi A.M. Male infertility and mitochondrial DNA. BiochemBiophys Res Commun. 2004;322(1):333-9. doi: 10.1016/j.bbrc.2004.07.112Carra E., Sangiorgi D., Gattuccio F., Rinaldi A.M. Male infertility and mitochondrial DNA. BiochemBiophys Res Commun. 2004;322(1):333-9. doi: 10.1016/j.bbrc.2004.07.112Bucci D., Spinaci M., Bustamante-Filho I.C., Nesci S. The sperm mitochondria: clues and challenges. AnimReprod. 2023;19(4):e20220131. doi: 10.1590/1984-3143-AR2022-0131].Bucci D., Spinaci M., Bustamante-Filho I.C., Nesci S. The sperm mitochondria: clues and challenges. AnimReprod. 2023;19(4):e20220131. doi: 10.1590/1984-3143-AR2022-0131].Ruiz-Pesini E., Lapeña A.C., Díez-Sánchez C., et al. Human mtDNA haplogroups associated with high or reduced spermatozoa motility. Am J Hum Genet. 2000;67(3):682-96. doi: 10.1086/303040].Ruiz-Pesini E., Lapeña A.C., Díez-Sánchez C., et al. Human mtDNA haplogroups associated with high or reduced spermatozoa motility. Am J Hum Genet. 2000;67(3):682-96. doi: 10.1086/303040].Holt I.J., Harding A.E., Morgan-Hughes J.A. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature. 1988;331(6158):717-9. doi: 10.1038/331717a0].Holt I.J., Harding A.E., Morgan-Hughes J.A. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature. 1988;331(6158):717-9. doi: 10.1038/331717a0].Tengan C.H., Moraes C.T. Detection and analysis of mitochondrial DNA deletions by whole genome PCR. Biochem Mol Med. 1996; 58(1):130-4. doi: 10.1006/bmme.1996.0040.Tengan C.H., Moraes C.T. Detection and analysis of mitochondrial DNA deletions by whole genome PCR. Biochem Mol Med. 1996; 58(1):130-4. doi: 10.1006/bmme.1996.0040.Fromenty B., Manfredi G., Sadlock J., et al. Efficient and specific amplification of identified partial duplications of human mitochondrial DNA by long PCR. Biochim Biophys Acta. 1996;1308(3):222-30. doi: 10.1016/0167-4781(96)00110-8.Fromenty B., Manfredi G., Sadlock J., et al. Efficient and specific amplification of identified partial duplications of human mitochondrial DNA by long PCR. Biochim Biophys Acta. 1996;1308(3):222-30. doi: 10.1016/0167-4781(96)00110-8.Ieremiadou F, Rodakis GC. Correlation of the 4977 bp mitochondrial DNA deletion with human sperm dysfunction. BMC Res Notes. 2009;2:18. doi: 10.1186/1756-0500-2-18.Ieremiadou F, Rodakis GC. Correlation of the 4977 bp mitochondrial DNA deletion with human sperm dysfunction. BMC Res Notes. 2009;2:18. doi: 10.1186/1756-0500-2-18.Kao S.H., Chao H.T., Wei Y.H. Mitochondrial deoxyribonucleic acid 4977 bp deletion is associated with diminished fertility and motility of human sperm. BiolReprod. 1995;52:729-36.Kao S.H., Chao H.T., Wei Y.H. Mitochondrial deoxyribonucleic acid 4977 bp deletion is associated with diminished fertility and motility of human sperm. BiolReprod. 1995;52:729-36.Cummins J.M., Jequier A.M., Martin R., et al. Semen levels of mitochondrial DNA deletions in men attending an infertility clinic do not correlate with phenotype. Int J Androl 1998, 21:47-52.Cummins J.M., Jequier A.M., Martin R., et al. Semen levels of mitochondrial DNA deletions in men attending an infertility clinic do not correlate with phenotype. Int J Androl 1998, 21:47-52.St John J.C., Jokhi R..P, Barratt C.L. Men with oligoasthenoteratozoospermia harbor higher numbers of multiple mitochondrial DNA deletions in their spermatozoa, but individual deletions are not indicative of overall aetiology. Mol Hum Reprod 2001, 7:103-111.St John J.C., Jokhi R..P, Barratt C.L. Men with oligoasthenoteratozoospermia harbor higher numbers of multiple mitochondrial DNA deletions in their spermatozoa, but individual deletions are not indicative of overall aetiology. Mol Hum Reprod 2001, 7:103-111.O’Connell M., McClure N., Lewis S.E. A comparison of mitochondrial and nuclear DNA status in testicular sperm from fertile men and those with obstructive azoospermia. Hum Reprod 2002, 17:1571-15717.O’Connell M., McClure N., Lewis S.E. A comparison of mitochondrial and nuclear DNA status in testicular sperm from fertile men and those with obstructive azoospermia. Hum Reprod 2002, 17:1571-15717.Reynier P., Chretien M.F., Savagner F., et al. Long PCR analysis of human gamete mtDNA suggests defective mitochondrial maintenance in spermatozoa and supports the bottleneck theory for oocytes. Biochem Biophys Res Commun 1998, 252:373-377.Reynier P., Chretien M.F., Savagner F., et al. Long PCR analysis of human gamete mtDNA suggests defective mitochondrial maintenance in spermatozoa and supports the bottleneck theory for oocytes. Biochem Biophys Res Commun 1998, 252:373-377.Stefano G.B., Bjenning C., Wang F., et al. Mitochondrial Heteroplasmy. Adv Exp Med Biol. 2017;982:577-594. doi: 10.1007/978-3319-55330-6_30.Stefano G.B., Bjenning C., Wang F., et al. Mitochondrial Heteroplasmy. Adv Exp Med Biol. 2017;982:577-594. doi: 10.1007/978-3319-55330-6_30.Schon E.A. Mitochondrial genetics and disease. Trends Biochem Sci. 2000;25(11):555-60. doi: 10.1016/s0968-0004(00)01688-1Schon E.A. Mitochondrial genetics and disease. Trends Biochem Sci. 2000;25(11):555-60. doi: 10.1016/s0968-0004(00)01688-1Cormier-Daire V., Bonnefont J.P., Rustin P., et al. Mitochondrial DNA rearrangements with onset as chronic diarrhea with villous atrophy. J Pediatr. 1994;124(1):63-70. doi: 10.1016/s00223476(94)70255-1.Cormier-Daire V., Bonnefont J.P., Rustin P., et al. Mitochondrial DNA rearrangements with onset as chronic diarrhea with villous atrophy. J Pediatr. 1994;124(1):63-70. doi: 10.1016/s00223476(94)70255-1.Cavelier L., Johannisson A., Gyllensten U. Analysis of mtDNA copy number and composition of single mitochondrial particles using flow cytometry and PCR. Exp Cell Res. 2000;259(1):79-85. doi: 10.1006/excr.2000.4949.Cavelier L., Johannisson A., Gyllensten U. Analysis of mtDNA copy number and composition of single mitochondrial particles using flow cytometry and PCR. Exp Cell Res. 2000;259(1):79-85. doi: 10.1006/excr.2000.4949.May-Panloup P., Chrétien M.F., Savagner F., et al. Increased sperm mitochondrial DNA content in male infertility. HumReprod. 2003;18(3):550-6. doi: 10.1093/humrep/deg096.May-Panloup P., Chrétien M.F., Savagner F., et al. Increased sperm mitochondrial DNA content in male infertility. HumReprod. 2003;18(3):550-6. doi: 10.1093/humrep/deg096.Díez-Sánchez C., Ruiz-Pesini E., Lapeña A.C., et al. Mitochondrial DNA content of human spermatozoa. Biol Reprod. 2003;68(1):1805. doi: 10.1095/biolreprod.102.005140Díez-Sánchez C., Ruiz-Pesini E., Lapeña A.C., et al. Mitochondrial DNA content of human spermatozoa. Biol Reprod. 2003;68(1):1805. doi: 10.1095/biolreprod.102.005140Amaral A., Ramalho-Santos J., St John J.C. The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm. Hum Reprod. 2007; 22(6):1585-96. doi: 10.1093/humrep/dem030.Amaral A., Ramalho-Santos J., St John J.C. The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm. Hum Reprod. 2007; 22(6):1585-96. doi: 10.1093/humrep/dem030.Song G.J., Lewis V. Mitochondrial DNA integrity and copy number in sperm from infertile men. Fertil Steril. 2008;90(6):2238-44. doi: 10.1016/j.fertnstert.2007.10.059Song G.J., Lewis V. Mitochondrial DNA integrity and copy number in sperm from infertile men. Fertil Steril. 2008;90(6):2238-44. doi: 10.1016/j.fertnstert.2007.10.059Tian M., Bao H., Martin F.L., et al. Association of DNA methylation and mitochondrial DNA copy number with human semen quality. Biol Reprod. 2014; 91(4):101. doi: 10.1095/biolreprod.114.122465.Tian M., Bao H., Martin F.L., et al. Association of DNA methylation and mitochondrial DNA copy number with human semen quality. Biol Reprod. 2014; 91(4):101. doi: 10.1095/biolreprod.114.122465.Wu H., Whitcomb B.W., Huffman A., et al. Associations of sperm mitochondrial DNA copy number and deletion rate with fertilization and embryo development in a clinical setting. Hum Reprod. 2019; 1;34(1):163-170. doi: 10.1093/humrep/dey330.Wu H., Whitcomb B.W., Huffman A., et al. Associations of sperm mitochondrial DNA copy number and deletion rate with fertilization and embryo development in a clinical setting. Hum Reprod. 2019; 1;34(1):163-170. doi: 10.1093/humrep/dey330.Tímermans A., Otero F., Garrido M, et al. The relationship between sperm nuclear DNA fragmentation, mitochondrial DNA fragmentation, and copy number in normal and abnormal human ejaculates. Andrology. 2023 Oct 2. doi: 10.1111/andr.13539.Tímermans A., Otero F., Garrido M, et al. The relationship between sperm nuclear DNA fragmentation, mitochondrial DNA fragmentation, and copy number in normal and abnormal human ejaculates. Andrology. 2023 Oct 2. doi: 10.1111/andr.13539.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):e0168823Zhang 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):e0168823St John J.C., Facucho-Oliveira J., Jiang Y., et al. Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells. Hum Reprod Update. 2010;16(5):488-509. doi: 10.1093/humupd/dmq002.St John J.C., Facucho-Oliveira J., Jiang Y., et al. Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells. Hum Reprod Update. 2010;16(5):488-509. doi: 10.1093/humupd/dmq002.Hecht N.B., Liem H., Kleene K.C., et al. Maternal inheritance of the mouse mitochondrial genome is not mediated by a loss or gross alteration of the paternal mitochondrial DNA or by methylation of the oocyte mitochondrial DNA. DevBiol. 1984;102(2):452-61. doi: 10.1016/0012-1606(84)90210-0.Hecht N.B., Liem H., Kleene K.C., et al. Maternal inheritance of the mouse mitochondrial genome is not mediated by a loss or gross alteration of the paternal mitochondrial DNA or by methylation of the oocyte mitochondrial DNA. DevBiol. 1984;102(2):452-61. doi: 10.1016/0012-1606(84)90210-0.Solovova O.A., Chernykh V.B. Genetics of Oocyte Maturation Defects and Early Embryo Development Arrest. Genes (Basel). 2022;13(11):1920. doi: 10.3390/genes13111920.Solovova O.A., Chernykh V.B. Genetics of Oocyte Maturation Defects and Early Embryo Development Arrest. Genes (Basel). 2022;13(11):1920. doi: 10.3390/genes13111920.Королькова А.И., Мишиева Н.Г., Мартазанова Б.А., Бурменская О.В., Веюкова М.А., Екимов А.Н., Трофимов Д.Ю., Абубакиров А.Н. Значимость копийности митохондриальной ДНК в клетках кумулюса пациенток позднего репродуктивного возраста. Акушерство и гинекология. 2019; 10: 108-114.Королькова А.И., Мишиева Н.Г., Мартазанова Б.А., Бурменская О.В., Веюкова М.А., Екимов А.Н., Трофимов Д.Ю., Абубакиров А.Н. Значимость копийности митохондриальной ДНК в клетках кумулюса пациенток позднего репродуктивного возраста. Акушерство и гинекология. 2019; 10: 108-114.Сыркашева А.Г., Красный А.М., Майорова Т.Д., Макарова Н.П., Долгушина Н.В. Изучение числа копий митохондриальной ДНК в ооцитах человека с различными морфологическими аномалиями. Молекулярная медицина. 2016; 14(5): 37-41.Сыркашева А.Г., Красный А.М., Майорова Т.Д., Макарова Н.П., Долгушина Н.В. Изучение числа копий митохондриальной ДНК в ооцитах человека с различными морфологическими аномалиями. Молекулярная медицина. 2016; 14(5): 37-41.Лисицына О.И., Долгушина Н.В., Макарова Н.П., Бурменская О.В. Митохондриальная ДНК как маркер качества гамет и эмбрионов в программах вспомогательных репродуктивных технологий. Акушерство и гинекология. 2023; 7: 20-26.Лисицына О.И., Долгушина Н.В., Макарова Н.П., Бурменская О.В. Митохондриальная ДНК как маркер качества гамет и эмбрионов в программах вспомогательных репродуктивных технологий. Акушерство и гинекология. 2023; 7: 20-26.Lee H.C., Yin P.H., Lu C.Y., et al. Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J. 2000;348(Pt 2):425-32.Lee H.C., Yin P.H., Lu C.Y., et al. Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J. 2000;348(Pt 2):425-32.Abasalt H.C., Gholamali J.S., Maryam G.C. Lipid peroxidation and large-scale deletions of mitochondrial DNA in asthenoteratozoospermic patients. Indian J Biochem Biophys. 2013;50(6):492-9.Abasalt H.C., Gholamali J.S., Maryam G.C. Lipid peroxidation and large-scale deletions of mitochondrial DNA in asthenoteratozoospermic patients. Indian J Biochem Biophys. 2013;50(6):492-9.Bonanno O., Romeo G., Asero P., et al. Sperm of patients with severe asthenozoospermia show biochemical, molecular and genomic alterations. Reproduction. 2016;152(6):695-704. doi: 10.1530/REP-160342.Bonanno O., Romeo G., Asero P., et al. Sperm of patients with severe asthenozoospermia show biochemical, molecular and genomic alterations. Reproduction. 2016;152(6):695-704. doi: 10.1530/REP-160342.Gabriel M.S., Chan S.W., Alhathal N., et al. Influence of microsurgical varicocelectomy on human sperm mitochondrial DNA copy number: a pilot study. J Assist Reprod Genet. 2012;29(8):759-64. doi: 10.1007/s10815-012-9785-z.Gabriel M.S., Chan S.W., Alhathal N., et al. Influence of microsurgical varicocelectomy on human sperm mitochondrial DNA copy number: a pilot study. J Assist Reprod Genet. 2012;29(8):759-64. doi: 10.1007/s10815-012-9785-z.Oluwayiose O.A., Josyula S., Houle E., et al. Association between sperm mitochondarial DNA copy number and nuclear DNA methylation. Epigenomics. 2020;12(24):2141-2153. doi: 10.2217/epi-20200253.Oluwayiose O.A., Josyula S., Houle E., et al. Association between sperm mitochondarial DNA copy number and nuclear DNA methylation. Epigenomics. 2020;12(24):2141-2153. doi: 10.2217/epi-20200253.Tiegs A.W., Tao X., Landis J., et al. Sperm Mitochondrial DNA Copy Number Is Not a Predictor of Intracytoplasmic Sperm Injection (ICSI) Cycle Outcomes. Reprod Sci. 2020;27(6):1350-1356. doi: 10.1007/s43032-020-00163-0.Tiegs A.W., Tao X., Landis J., et al. Sperm Mitochondrial DNA Copy Number Is Not a Predictor of Intracytoplasmic Sperm Injection (ICSI) Cycle Outcomes. Reprod Sci. 2020;27(6):1350-1356. doi: 10.1007/s43032-020-00163-0.Rosati A.J., Whitcomb B.W., Brandon N., et al. Sperm mitochondrial DNA biomarkers and couple fecundity. Hum Reprod. 2020;1;35(11):2619-2625. doi: 10.1093/humrep/deaa191.Rosati A.J., Whitcomb B.W., Brandon N., et al. Sperm mitochondrial DNA biomarkers and couple fecundity. Hum Reprod. 2020;1;35(11):2619-2625. doi: 10.1093/humrep/deaa191.Danan C., Sternberg D., Van Steirteghem A., et al. Evaluation of parental mitochondrial inheritance in neonates born after intracytoplasmic sperm injection. Am J Hum Genet. 1999; 65(2):463-73. doi: 10.1086/302484.Danan C., Sternberg D., Van Steirteghem A., et al. Evaluation of parental mitochondrial inheritance in neonates born after intracytoplasmic sperm injection. Am J Hum Genet. 1999; 65(2):463-73. doi: 10.1086/302484.St John J., Sakkas D., Dimitriadi K., et al. Failure of elimination of paternal mitochondrial DNA in abnormal embryos. Lancet. 2000;15;355(9199):200. doi: 10.1016/s0140-6736(99)03842-8.St John J., Sakkas D., Dimitriadi K., et al. Failure of elimination of paternal mitochondrial DNA in abnormal embryos. Lancet. 2000;15;355(9199):200. doi: 10.1016/s0140-6736(99)03842-8.

The authors declare that there are no conflicts of interest present.