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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2014

Open Access 01-12-2014 | Research

Infertile men older than 40 years are at higher risk of sperm DNA damage

Authors: Saad Alshahrani, Ashok Agarwal, Mourad Assidi, Adel M Abuzenadah, Damayanthi Durairajanayagam, Ahmet Ayaz, Rakesh Sharma, Edmund Sabanegh

Published in: Reproductive Biology and Endocrinology | Issue 1/2014

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Abstract

Background

The effect of paternal age on semen quality is controversial. In this retrospective study, the aim was to investigate the effects of advancing age on sperm parameters including reactive oxygen species (ROS), total antioxidant capacity (TAC) and sperm DNA damage in infertile men. We also examined whether paternal age >40 y is associated with higher risk of sperm DNA damage.

Methods

A total of 472 infertile men presenting for infertility were divided into 4 age groups: group A: patients ≤ 30 y; group B: patients 31- 40 y, group C: ≤ 40 y and group D: patients >40 y. The following tests were performed - semen analysis according to WHO 2010 criteria, seminal ROS by chemiluminescence, TAC by colorimetric assay and sperm DNA damage by TUNEL assay - and the results were compared amongst the 4 age groups.

Results

There was no statistical difference in conventional semen parameters, TAC and ROS with advancing paternal age as well as between different age groups. However, a significant negative association was noted between sperm DNA damage and advancing paternal age. Men >40 y showed higher levels of sperm DNA damage (24.4 ± 18.5%) compared to younger men (<30 y; 16.7 ± 11.2%; p <0.05).

Conclusions

Infertile men over the age of 40 y have a greater percentage of sperm DNA fragmentation compared to infertile men aged 40 y and below. Advanced paternal age (>40 y) may increase the risk of sperm DNA damage in infertile men.
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Literature
1.
Charlton BG: Psychological neoteny and higher education: associations with delayed parenthood. Med Hypotheses. 2007, 69: 237-240. 10.1016/j.mehy.2007.03.005.CrossRefPubMed
2.
Kovac JR, Addai J, Smith RP, Coward RM, Lamb DJ, Lipshultz LI: The effects of advanced paternal age on fertility. Asian J Androl. 2013, 15: 723-728. 10.1038/aja.2013.92.PubMedCentralCrossRefPubMed
3.
Pasqualotto FF, Borges Junior E, Pasqualotto EB: The male biological clock is ticking: a review of the literature. Sao Paulo Med J. 2008, 126: 197-201.CrossRefPubMed
4.
Mac Dougall K, Beyene Y, Nachtigall RD: ‘Inconvenient biology’: advantages and disadvantages of first-time parenting after age 40 using in vitro fertilization. Hum Reprod. 2012, 27: 1058-1065. 10.1093/humrep/des007.PubMedCentralCrossRefPubMed
5.
Bray I, Gunnell D, Davey Smith G: Advanced paternal age: how old is too old?. J Epidemiol Community Health. 2006, 60: 851-853. 10.1136/jech.2005.045179.PubMedCentralCrossRefPubMed
6.
Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Kirmeyer S, Mathews TJ, Wilson EC: Births: final data for 2009. Natl Vital Stat Rep. 2011, 60: 1-70.PubMed
7.
Lansac J: Delayed parenting. Is delayed childbearing a good thing?. Hum Reprod. 1995, 10: 1033-1035.PubMed
8.
9.
Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M: Maternal age and fetal loss: population based register linkage study. BMJ. 2000, 320: 1708-1712. 10.1136/bmj.320.7251.1708.CrossRefPubMed
10.
de la Rochebrochard E, Thonneau P: Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod. 2002, 17: 1649-1656. 10.1093/humrep/17.6.1649.CrossRefPubMed
11.
Homonnai ZT, Fainman N, David MP, Paz GF: Semen quality and sex hormone pattern of 29 middle aged men. Andrologia. 1982, 14: 164-170.CrossRefPubMed
12.
Auger J, Kunstmann JM, Czyglik F, Jouannet P: Decline in semen quality among fertile men in Paris during the past 20 years. N Engl J Med. 1995, 332: 281-285. 10.1056/NEJM199502023320501.CrossRefPubMed
13.
Fisch H, Goluboff ET, Olson JH, Feldshuh J, Broder SJ, Barad DH: Semen analyses in 1,283 men from the United States over a 25-year period: no decline in quality. Fertil Steril. 1996, 65: 1009-1014.PubMed
14.
Kidd SA, Eskenazi B, Wyrobek AJ: Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001, 75: 237-248. 10.1016/S0015-0282(00)01679-4.CrossRefPubMed
15.
Eskenazi B, Wyrobek AJ, Sloter E, Kidd SA, Moore L, Young S, Moore D: The association of age and semen quality in healthy men. Hum Reprod. 2003, 18: 447-454. 10.1093/humrep/deg107.CrossRefPubMed
16.
Schwartz D, Mayaux MJ, Spira A, Moscato ML, Jouannet P, Czyglik F, David G: Semen characteristics as a function of age in 833 fertile men. Fertil Steril. 1983, 39: 530-535.PubMed
17.
Cardona Maya W, Berdugo J, Cadavid Jaramillo A: The effects of male age on semen parameters: analysis of 1364 men attending an andrology center. Aging Male. 2009, 12: 100-103. 10.3109/13685530903322841.CrossRefPubMed
18.
Li Y, Lin H, Li Y, Cao J: Association between socio-psycho-behavioral factors and male semen quality: systematic review and meta-analyses. Fertil Steril. 2011, 95: 116-123. 10.1016/j.fertnstert.2010.06.031.CrossRefPubMed
19.
Gao J, Gao ES, Yang Q, Walker M, Wu JQ, Zhou WJ, Wen SW: Semen quality in a residential, geographic and age representative sample of healthy Chinese men. Hum Reprod. 2007, 22: 477-484.CrossRefPubMed
20.
Sobreiro BP, Lucon AM, Pasqualotto FF, Hallak J, Athayde KS, Arap S: Semen analysis in fertile patients undergoing vasectomy: reference values and variations according to age, length of sexual abstinence, seasonality, smoking habits and caffeine intake. Sao Paulo Med J. 2005, 123: 161-166. 10.1590/S1516-31802005000400002.CrossRefPubMed
21.
Winkle T, Rosenbusch B, Gagsteiger F, Paiss T, Zoller N: The correlation between male age, sperm quality and sperm DNA fragmentation in 320 men attending a fertility center. J Assist Reprod Genet. 2009, 26: 41-46. 10.1007/s10815-008-9277-3.PubMedCentralCrossRefPubMed
22.
Cocuzza M, Athayde KS, Agarwal A, Sharma R, Pagani R, Lucon AM, Srougi M, Hallak J: Age-related increase of reactive oxygen species in neat semen in healthy fertile men. Urology. 2008, 71: 490-494. 10.1016/j.urology.2007.11.041.CrossRefPubMed
23.
Brahem S, Mehdi M, Elghezal H, Saad A: The effects of male aging on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population. J Assist Reprod Genet. 2011, 28: 425-432. 10.1007/s10815-011-9537-5.PubMedCentralCrossRefPubMed
24.
Nijs M, De Jonge C, Cox A, Janssen M, Bosmans E, Ombelet W: Correlation between male age, WHO sperm parameters, DNA fragmentation, chromatin packaging and outcome in assisted reproduction technology. Andrologia. 2011, 43: 174-179. 10.1111/j.1439-0272.2010.01040.x.CrossRefPubMed
25.
Plastira K, Msaouel P, Angelopoulou R, Zanioti K, Plastiras A, Pothos A, Bolaris S, Paparisteidis N, Mantas D: The effects of age on DNA fragmentation, chromatin packaging and conventional semen parameters in spermatozoa of oligoasthenoteratozoospermic patients. J Assist Reprod Genet. 2007, 24: 437-443. 10.1007/s10815-007-9162-5.PubMedCentralCrossRefPubMed
26.
Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S, Rabinowitz J, Shulman C, Malaspina D, Lubin G, Knobler HY, Davidson M, Susser E: Advancing paternal age and autism. Arch Gen Psychiatry. 2006, 63: 1026-1032. 10.1001/archpsyc.63.9.1026.CrossRefPubMed
27.
Sloter ED, Marchetti F, Eskenazi B, Weldon RH, Nath J, Cabreros D, Wyrobek AJ: Frequency of human sperm carrying structural aberrations of chromosome 1 increases with advancing age. Fertil Steril. 2007, 87: 1077-1086. 10.1016/j.fertnstert.2006.08.112.CrossRefPubMed
28.
Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, Feldman D, Susser ES: Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry. 2001, 58: 361-367. 10.1001/archpsyc.58.4.361.CrossRefPubMed
29.
Toriello HV, Meck JM, Professional P, Guidelines C: Statement on guidance for genetic counseling in advanced paternal age. Genet Med. 2008, 10: 457-460. 10.1097/GIM.0b013e318176fabb.PubMedCentralCrossRefPubMed
30.
Slama R, Bouyer J, Windham G, Fenster L, Werwatz A, Swan SH: Influence of paternal age on the risk of spontaneous abortion. Am J Epidemiol. 2005, 161: 816-823. 10.1093/aje/kwi097.CrossRefPubMed
31.
Kleinhaus K, Perrin M, Friedlander Y, Paltiel O, Malaspina D, Harlap S: Paternal age and spontaneous abortion. Obstet Gynecol. 2006, 108: 369-377. 10.1097/01.AOG.0000224606.26514.3a.CrossRefPubMed
32.
33.
de La Rochebrochard E, Thonneau P: Paternal age > or = 40 years: an important risk factor for infertility. Am J Obstet Gynecol. 2003, 189: 901-905. 10.1067/S0002-9378(03)00753-1.CrossRefPubMed
34.
De La Rochebrochard E, Thonneau P: Paternal age: are the risks of infecundity and miscarriage higher when the man is aged 40 years or over?. Rev Epidemiol Sante Publique. 2005, 53 Spec No 2: 2S47-2S55.PubMed
35.
Singh NP, Muller CH, Berger RE: Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril. 2003, 80: 1420-1430. 10.1016/j.fertnstert.2003.04.002.CrossRefPubMed
36.
Donnelly ET, O’Connell M, McClure N, Lewis SE: Differences in nuclear DNA fragmentation and mitochondrial integrity of semen and prepared human spermatozoa. Hum Reprod. 2000, 15: 1552-1561. 10.1093/humrep/15.7.1552.CrossRefPubMed
37.
Sun JG, Jurisicova A, Casper RF: Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro. Biol Reprod. 1997, 56: 602-607. 10.1095/biolreprod56.3.602.CrossRefPubMed
38.
Zini A, Boman JM, Belzile E, Ciampi A: Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008, 23: 2663-2668. 10.1093/humrep/den321.CrossRefPubMed
39.
Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D: Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril. 2004, 82: 378-383. 10.1016/j.fertnstert.2003.12.039.CrossRefPubMed
40.
Aitken RJ, Krausz C: Oxidative stress, DNA damage and the Y chromosome. Reproduction. 2001, 122: 497-506. 10.1530/rep.0.1220497.CrossRefPubMed
41.
Varshini J, Srinag BS, Kalthur G, Krishnamurthy H, Kumar P, Rao SB, Adiga SK: Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men. Andrologia. 2012, 44 (Suppl 1): 642-649.CrossRefPubMed
42.
Moskovtsev SI, Willis J, Mullen JB: Age-related decline in sperm deoxyribonucleic acid integrity in patients evaluated for male infertility. Fertil Steril. 2006, 85: 496-499. 10.1016/j.fertnstert.2005.05.075.CrossRefPubMed
43.
Vagnini L, Baruffi RL, Mauri AL, Petersen CG, Massaro FC, Pontes A, Oliveira JB, Franco JG: The effects of male age on sperm DNA damage in an infertile population. Reprod Biomed Online. 2007, 15: 514-519. 10.1016/S1472-6483(10)60382-3.CrossRefPubMed
44.
World Health Organization: WHO Laboratory manual for the examination and processing of human semen. 2010, Geneva, Switzerland: WHO Press, 5
45.
Mahfouz R, Sharma R, Sharma D, Sabanegh E, Agarwal A: Diagnostic value of the total antioxidant capacity (TAC) in human seminal plasma. Fertil Steril. 2009, 91: 805-811. 10.1016/j.fertnstert.2008.01.022.CrossRefPubMed
46.
Kashou AH, Sharma R, Agarwal A: Assessment of oxidative stress in sperm and semen. Methods Mol Biol. 2013, 927: 351-361. 10.1007/978-1-62703-038-0_30.CrossRefPubMed
47.
Sharma RK, Sabanegh E, Mahfouz R, Gupta S, Thiyagarajan A, Agarwal A: TUNEL as a test for sperm DNA damage in the evaluation of male infertility. Urology. 2010, 76: 1380-1386. 10.1016/j.urology.2010.04.036.CrossRefPubMed
48.
Dain L, Auslander R, Dirnfeld M: The effect of paternal age on assisted reproduction outcome. Fertil Steril. 2011, 95: 1-8. 10.1016/j.fertnstert.2010.08.029.CrossRefPubMed
49.
Agarwal A, Makker K, Sharma R: Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol. 2008, 59: 2-11.CrossRefPubMed
50.
Lewis SE, Aitken RJ: DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell Tissue Res. 2005, 322: 33-41. 10.1007/s00441-005-1097-5.CrossRefPubMed
51.
Spano M, Bonde JP, Hjollund HI, Kolstad HA, Cordelli E, Leter G: Sperm chromatin damage impairs human fertility. The Danish first pregnancy planner study team. Fertil Steril. 2000, 73: 43-50. 10.1016/S0015-0282(99)00462-8.CrossRefPubMed
52.
Wyrobek AJ, Eskenazi B, Young S, Arnheim N, Tiemann-Boege I, Jabs EW, Glaser RL, Pearson FS, Evenson D: Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci U S A. 2006, 103: 9601-9606. 10.1073/pnas.0506468103.PubMedCentralCrossRefPubMed
53.
Rybar R, Kopecka V, Prinosilova P, Markova P, Rubes J: Male obesity and age in relationship to semen parameters and sperm chromatin integrity. Andrologia. 2011, 43: 286-291. 10.1111/j.1439-0272.2010.01057.x.CrossRefPubMed
54.
Schmid TE, Eskenazi B, Baumgartner A, Marchetti F, Young S, Weldon R, Anderson D, Wyrobek AJ: The effects of male age on sperm DNA damage in healthy non-smokers. Hum Reprod. 2007, 22: 180-187.CrossRefPubMed
55.
De La Rochebrochard E, McElreavey K, Thonneau P: Paternal age over 40 years: the “amber light” in the reproductive life of men?. J Androl. 2003, 24: 459-465.PubMed
56.
Hellstrom WJ, Overstreet JW, Sikka SC, Denne J, Ahuja S, Hoover AM, Sides GD, Cordell WH, Harrison LM, Whitaker JS: Semen and sperm reference ranges for men 45 years of age and older. J Androl. 2006, 27: 421-428. 10.2164/jandrol.05156.CrossRefPubMed
57.
World Health Organization (WHO: WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. 1999, Cambridge University: Press, 4
58.
de La Rochebrochard E, de Mouzon J, Thepot F, Thonneau P, French National IVFRA: Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France. Fertil Steril. 2006, 85: 1420-1424. 10.1016/j.fertnstert.2005.11.040.CrossRefPubMed
59.
Li Z, Wang L, Cai J, Huang H: Correlation of sperm DNA damage with IVF and ICSI outcomes: a systematic review and meta-analysis. J Assist Reprod Genet. 2006, 23: 367-376. 10.1007/s10815-006-9066-9.PubMedCentralCrossRefPubMed
60.
Liu K, Case A: Advanced reproductive age and fertility. J Obstet Gynaecol Can. 2011, 33: 1165-1175.PubMed
61.
Belloc S, Benkhalifa M, Cohen-Bacrie M, Dalleac A, Amar E, Zini A: Sperm deoxyribonucleic acid damage in normozoospermic men is related to age and sperm progressive motility. Fertil Steril. 2014, 101: 1588-1593. 10.1016/j.fertnstert.2014.02.006.CrossRefPubMed
62.
Cabry R, Merviel P, Hazout A, Belloc S, Dalleac A, Copin H, Benkhalifa M: Management of infertility in women over 40. Maturitas. 2014, 78: 17-21. 10.1016/j.maturitas.2014.02.014.CrossRefPubMed
63.
Belloc S, Benkhalifa M, Cohen-Bacrie M, Dalleac A, Chahine H, Amar E, Zini A: Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation. J Assist Reprod Genet. 2014, 31: 527-532. 10.1007/s10815-014-0194-3.PubMedCentralCrossRefPubMed
64.
Benkhalifa M, Ferreira YJ, Chahine H, Louanjli N, Miron P, Merviel P, Copin H: Mitochondria: participation to infertility as source of energy and cause of senescence. Int J Biochem Cell Biol. 2014, 21: 60-64.CrossRef
65.
Benkhalifa M, Montjean D, Belloc S, Dalleac A, Ducasse M, Boyer P, Merviel P, Copin H: Emerging molecular methods for male infertility investigation. Expert Rev Mol Diagn. 2014, 14: 37-45. 10.1586/14737159.2014.864558.CrossRefPubMed
66.
Bejarano I, Monllor F, Marchena AM, Ortiz A, Lozano G, Jiménez MI, Gaspar P, García JF, Pariente JA, Rodríguez AB, Espino J: Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa. J Pineal Res. 2014, 57: 333-339. 10.1111/jpi.12172.CrossRefPubMed
67.
Ortiz A, Espino J, Bejarano I, Lozano GM, Monllor F, García JF, Pariente JA, Rodríguez AB: High endogenous melatonin concentrations enhance sperm quality and short-term in vitro exposure to melatonin improves aspects of sperm motility. J Pineal Res. 2011, 50: 132-139.PubMed
68.
Espino J, Bejarano I, Ortiz A, Lozano GM, García JF, Pariente JA, Rodríguez AB: Melatonin as a potential tool against oxidative damage and apoptosis in ejaculated human spermatozoa. Fertil Steril. 2010, 94: 1915-1917. 10.1016/j.fertnstert.2009.12.082.CrossRefPubMed
69.
Lozano GM, Bejarano I, Espino J, González D, Ortiz A, García JF, Rodríguez AB, Pariente JA: Relationship between caspase activity and apoptotic markers in human sperm in response to hydrogen peroxide and progesterone. J Reprod Dev. 2009, 55: 615-621. 10.1262/jrd.20250.CrossRefPubMed
Metadata
Title
Infertile men older than 40 years are at higher risk of sperm DNA damage
Authors
Saad Alshahrani
Ashok Agarwal
Mourad Assidi
Adel M Abuzenadah
Damayanthi Durairajanayagam
Ahmet Ayaz
Rakesh Sharma
Edmund Sabanegh
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2014
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-12-103

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