Folic acid - influence on male fertility, spermatogenesis, sperm DNA fragmentation and subsequent growth of the embryo and fetus
DOI:
https://doi.org/10.12775/JEHS.2023.34.01.004Keywords
folic acid, spermatogenesis, male infertilityAbstract
Introduction: Men's infertility is a multifactorial disorder. According to scientific literature, among men with reduced fertility, growing interest in folic acid is observed.
This review describes the effect of folic acid on spermatogenesis, sperm concentration, sperm DNA fragmentation and the growth of the embryo and fetus.
Material and methods: The work was based on the articles published in PubMed, medical books and websites.
Results: Folic acid affects the trajectory of embryo growth in pregnancy conceived spontaneously, there is a negative correlation between the concentration of folic acid in the semen and the indicator of sperm DNA fragmentation and sperm concentration are statistically higher in folic acid supplements.
Conclusions: The results suggest that the father's exposure to folic acid before conception may affect the health of his offspring, and therefore care before conception should be changed from an approach focused on a woman to a couple-based approach.
References
Martín-Calvo N, Mínguez-Alarcón L, Gaskins AJ, Nassan FL, Williams PL, Souter I, Hauser R, Chavarro JE; EARTH Study team. Paternal preconception folate intake in relation to gestational age at delivery and birthweight of newborns conceived through assisted reproduction. Reprod Biomed Online. 2019 Nov;39(5):835-843. doi: 10.1016/j.rbmo.2019.07.005. Epub 2019 Jul 12. PMID: 31564651; PMCID: PMC6848767.
Hoek J, Koster MPH, Schoenmakers S, Willemsen SP, Koning AHJ, Steegers EAP, Steegers-Theunissen RPM. Does the father matter? The association between the periconceptional paternal folate status and embryonic growth. Fertil Steril. 2019 Feb;111(2):270-279. doi: 10.1016/j.fertnstert.2018.10.017. PMID: 30691629.
Cheng PJ, Pastuszak AW, Hotaling JM. Is it time to start folate supplementation in men? The effect of paternal folate status on embryonic growth. Fertil Steril. 2019 Feb;111(2):251-252. doi: 10.1016/j.fertnstert.2018.11.017. Epub 2018 Dec 28. PMID: 30598167.
Irani M, Amirian M, Sadeghi R, Lez JL, Latifnejad Roudsari R. The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis. Urol J. 2017 Aug 29;14(5):4069-4078. PMID: 28853101.
Wang W, Peng M, Yuan H, Liu C, Zhang Y, Fang Y, Su Y, Zhang X, Zhang H, Tang Y, Zhao K. Studying the mechanism of sperm DNA damage caused by folate deficiency. J Cell Mol Med. 2022 Feb;26(3):776-788. doi: 10.1111/jcmm.17119. Epub 2021 Dec 24. PMID: 34953021; PMCID: PMC8817123.
Raigani M, Yaghmaei B, Amirjannti N, Lakpour N, Akhondi MM, Zeraati H, Hajihosseinal M, Sadeghi MR. The micronutrient supplements, zinc sulphate and folic acid, did not ameliorate sperm functional parameters in oligoasthenoteratozoospermic men. Andrologia. 2014;46(9):956-62. doi: 10.1111/and.12180. Epub 2013 Oct 23. PMID: 24147895.
Yuan HF, Zhao K, Zang Y, Liu CY, Hu ZY, Wei JJ, Zhou T, Li Y, Zhang HP. Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis. Oncotarget. 2017 Apr 11;8(15):24130-24141. doi: 10.18632/oncotarget.15731. PMID: 28445960; PMCID: PMC5421833.
Chan D, McGraw S, Klein K, Wallock LM, Konermann C, Plass C, Chan P, Robaire B, Jacob RA, Greenwood CM, Trasler JM. Stability of the human sperm DNA methylome to folic acid fortification and short-term supplementation. Hum Reprod. 2017 Feb;32(2):272-283. doi: 10.1093/humrep/dew308. Epub 2016 Dec 18. PMID: 27994001; PMCID: PMC5260859.
Hoek J, Steegers-Theunissen RPM, Willemsen SP, Schoenmakers S. Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics: A Systematic Review and Meta-Analysis. Mol Nutr Food Res. 2020 May;64(9):e1900696. doi: 10.1002/mnfr.201900696. Epub 2020 Feb 20. PMID: 32032459; PMCID: PMC7317557.
Schisterman EF, Clemons T, Peterson CM, Johnstone E, Hammoud AO, Lamb D, Carrell DT, Perkins NJ, Sjaarda LA, Van Voorhis BJ, Ryan G, Summers K, Campbell B, Robins J, Chaney K, Mills JL, Mendola P, Chen Z, DeVilbiss EA, Mumford SL. A Randomized Trial to Evaluate the Effects of Folic Acid and Zinc Supplementation on Male Fertility and Livebirth: Design and Baseline Characteristics. Am J Epidemiol. 2020 Jan 31;189(1):8-26. doi: 10.1093/aje/kwz217. PMID: 31712803; PMCID: PMC8204144.
Boxmeer JC, Smit M, Utomo E, Romijn JC, Eijkemans MJ, Lindemans J, Laven JS, Macklon NS, Steegers EA, Steegers-Theunissen RP. Low folate in seminal plasma is associated with increased sperm DNA damage. Fertil Steril. 2009 Aug;92(2):548-56. doi: 10.1016/j.fertnstert.2008.06.010. Epub 2008 Aug 22. PMID: 18722602.
Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002 Mar;77(3):491-8. doi: 10.1016/s0015-0282(01)03229-0. PMID: 11872201.
Cueto HT, Jacobsen BH, Laursen ASD, Riis AH, Hatch EE, Wise LA, Trolle E, Sørensen HT, Rothman KJ, Wesselink AK, Willis S, Johannesen BR, Mikkelsen EM. Dietary folate intake and fecundability in two preconception cohorts. Hum Reprod. 2022 Apr 1;37(4):828-837. doi: 10.1093/humrep/deac002. PMID: 35051293; PMCID: PMC8971647.
Ly L, Chan D, Aarabi M, Landry M, Behan NA, MacFarlane AJ, Trasler J. Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation. Mol Hum Reprod. 2017 Jul 1;23(7):461-477. doi: 10.1093/molehr/gax029. PMID: 28535307; PMCID: PMC5909862.
Mathieu d'Argent E, Ravel C, Rousseau A, Morcel K, Massin N, Sussfeld J, Simon T, Antoine JM, Mandelbaume J, Daraï E, Kolanska K. High-Dose Supplementation of Folic Acid in Infertile Men Improves IVF-ICSI Outcomes: A Randomized Controlled Trial (FOLFIV Trial). J Clin Med. 2021 Apr 26;10(9):1876. doi: 10.3390/jcm10091876. PMID: 33925981; PMCID: PMC8123699.
Xie C, Ping P, Ma Y, Wu Z, Chen X. Correlation between methylenetetrahydrofolate reductase gene polymorphism and oligoasthenospermia and the effects of folic acid supplementation on semen quality. Transl Androl Urol. 2019 Dec;8(6):678-685. doi: 10.21037/tau.2019.11.17. PMID: 32038964; PMCID: PMC6987591.
Najafipour R, Moghbelinejad S, Aleyasin A, Jalilvand A. Effect of B9 and B12 vitamin intake on semen parameters and fertility of men with MTHFR polymorphisms. Andrology. 2017 Jul;5(4):704-710. doi: 10.1111/andr.12351. Epub 2017 Apr 25. PMID: 28440964.
Huang WJ, Lu XL, Li JT, Zhang JM. Effects of folic acid on oligozoospermia with MTHFR polymorphisms in term of seminal parameters, DNA fragmentation, and live birth rate: a double-blind, randomized, placebo-controlled trial. Andrology. 2020 Jan;8(1):110-116. doi: 10.1111/andr.12652. Epub 2019 May 24. PMID: 31127676.
Chan D, Shao X, Dumargne MC, Aarabi M, Simon MM, Kwan T, Bailey JL, Robaire B, Kimmins S, San Gabriel MC, Zini A, Librach C, Moskovtsev S, Grundberg E, Bourque G, Pastinen T, Trasler JM. Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism. Environ Health Perspect. 2019 Aug;127(8):87002. doi: 10.1289/EHP4812. Epub 2019 Aug 8. PMID: 31393794; PMCID: PMC6792365.
González-Rodríguez LG, López-Sobaler AM, Perea Sánchez JM, Ortega RM. Nutrición y fertilidad [Nutrition and fertility]. Nutr Hosp. 2018 Sep 7;35(Spec No6):7-10. Spanish. doi: 10.20960/nh.2279. PMID: 30351153.
Al Omrani B, Al Eisa N, Javed M, Al Ghedan M, Al Matrafi H, Al Sufyan H. Associations of sperm DNA fragmentation with lifestyle factors and semen parameters of Saudi men and its impact on ICSI outcome. Reprod Biol Endocrinol. 2018 May 19;16(1):49. doi: 10.1186/s12958-018-0369-3. PMID: 29778100; PMCID: PMC5960110.
Mumford SL, Johnstone E, Kim K, Ahmad M, Salmon S, Summers K, Chaney K, Ryan G, Hotaling JM, Purdue-Smithe AC, Chen Z, Clemons T. A Prospective Cohort Study to Evaluate the Impact of Diet, Exercise, and Lifestyle on Fertility: Design and Baseline Characteristics. Am J Epidemiol. 2020 Nov 2;189(11):1254-1265. doi: 10.1093/aje/kwaa073. PMID: 32472141; PMCID: PMC7604525.
Liu KS, Mao XD, Pan F, An RF. Effect and mechanisms of reproductive tract infection on oxidative stress parameters, sperm DNA fragmentation, and semen quality in infertile males. Reprod Biol Endocrinol. 2021 Jun 28;19(1):97. doi: 10.1186/s12958-021-00781-6. PMID: 34183027; PMCID: PMC8237428.
Ahmadi S, Bashiri R, Ghadiri-Anari A, Nadjarzadeh A. Antioxidant supplements and semen parameters: An evidence based review. Int J Reprod Biomed. 2016 Dec;14(12):729-736. PMID: 28066832; PMCID: PMC5203687.
Mahajan A, Sapehia D, Thakur S, Mohanraj PS, Bagga R, Kaur J. Effect of imbalance in folate and vitamin B12 in maternal/parental diet on global methylation and regulatory miRNAs. Sci Rep. 2019 Nov 26;9(1):17602. doi: 10.1038/s41598-019-54070-9. PMID: 31772242; PMCID: PMC6879517.
Aarabi M, Christensen KE, Chan D, Leclerc D, Landry M, Ly L, Rozen R, Trasler J. Testicular MTHFR deficiency may explain sperm DNA hypomethylation associated with high dose folic acid supplementation. Hum Mol Genet. 2018 Apr 1;27(7):1123-1135. doi: 10.1093/hmg/ddy021. PMID: 29360980; PMCID: PMC6159534.
Perrier F, Viallon V, Ambatipudi S, Ghantous A, Cuenin C, Hernandez-Vargas H, Chajès V, Baglietto L, Matejcic M, Moreno-Macias H, Kühn T, Boeing H, Karakatsani A, Kotanidou A, Trichopoulou A, Sieri S, Panico S, Fasanelli F, Dolle M, Onland-Moret C, Sluijs I, Weiderpass E, Quirós JR, Agudo A, Huerta JM, Ardanaz E, Dorronsoro M, Tong TYN, Tsilidis K, Riboli E, Gunter MJ, Herceg Z, Ferrari P, Romieu I. Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study. Clin Epigenetics. 2019 Apr 2;11(1):57. doi: 10.1186/s13148-019-0637-x. PMID: 30940212; PMCID: PMC6444439.
Szukiewicz D., Układ Płciowy. W: red. nauk. Maśliński S., Ryżewski J., Patofizjologia. T.2. Warszawa 2022.
Shi F, Zhang Z, Cui H, Wang J, Wang Y, Tang Y, Yang W, Zou P, Ling X, Han F, Liu J, Chen Q, Liu C, Cao J, Ao L. Analysis by transcriptomics and metabolomics for the proliferation inhibition and dysfunction through redox imbalance-mediated DNA damage response and ferroptosis in male reproduction of mice and TM4 Sertoli cells exposed to PM2.5. Ecotoxicol Environ Saf. 2022 Jun 15;238:113569. doi: 10.1016/j.ecoenv.2022.113569. Epub 2022 May 2. PMID: 35512470.
Ziaeipour S, Ahrabi B, Naserzadeh P, Aliaghaei A, Sajadi E, Abbaszadeh HA, Amini A, Abdi S, Darabi S, Abdollahifar MA. Effects of Sertoli Cell Transplantation on Spermatogenesis in Azoospermic Mice. Cell Physiol Biochem. 2019;52(3):421-434. doi: 10.33594/000000030. Epub 2019 Mar 8. PMID: 30845381.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Monika Truchta, Kinga Augustynowicz, Marta Marcinkowska, Michał Stoliński, Kinga Świąder
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 415
Number of citations: 0