akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2025.687akusherstvo-2598Research ArticleREVIEW ARTICLESНАУЧНЫЕ ОБЗОРЫMyoinositol and D-chiroinositol in combination with folates and manganese as factors of male health: effect on sperm structure and fertilityМиоинозитол и D-хироинозитол в комплексе с фолатами и марганцем как факторы мужского здоровья: воздействие на структуру и фертильность сперматозоидовhttps://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Громова Ольга Алексеевна - д.м.н., проф. Scopus Author ID: 7003589812. WoS ResearcherID: J-4946-2017.

119333 Москва, ул. Вавилова, д. 44, корп. 2

Olga A. Gromova - MD, Dr Sci Med, Prof. Scopus Author ID: 7003589812. WoS ResearcherID: J-4946-2017.

44 bldg. 2, Vavilova Str., Moscow 119333

unesco.gromova@gmail.comhttps://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

Торшин Иван Юрьевич - к.ф.-м.н., к.х.н. Scopus Author ID: 7003300274. WoS ResearcherID: C-7683-2018.

119333 Москва, ул. Вавилова, д. 44, корп. 2

Ivan Yu. Torshin - MD, PhD in Physics and Mathematics, PhD in Chemistry. Scopus Author ID: 7003300274. WoS ResearcherID: C-7683-2018.

44 bldg. 2, Vavilova Str., Moscow 119333

https://orcid.org/0000-0001-5309-0087ТапильскаяН. И.TapilskayaN. I.

Наталья Игоревна Тапильская - д.м.н., проф. Scopus Author ID: 23013489000. WoS ResearcherID: A-7504-2016.

199034 Санкт-Петербург, Менделеевская линия, д. 3

Natalia I. Tapilskaya - MD, Dr Sci Med, Prof. Scopus Author ID: 23013489000. WoS ResearcherID: A-7504-2016.

3 Mendeleevskaya Liniya, Saint Petersburg 199034

ФГУ «Федеральный исследовательский центр "Информатика и управление" Российской академии наук»РоссияFederal Research Center «Computer Science and Control», Russian Academy of SciencesRussian FederationФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»РоссияOtt Research Institute of Obstetrics, Gynecology and ReproductologyRussian Federation202512112025195737757Copyright © Gromova O.A., Torshin I.Y., Tapilskaya N.I., 20252025Громова О.А., Торшин И.Ю., Тапильская Н.И.Gromova O.A., Torshin I.Y., Tapilskaya N.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/2598

An important factor of secondary male infertility is deficiency of vitamins and microelements. In the present work, a set of studies on myoinositol (MI), D-chiroinositol (DCI), their synergists (folates, manganese ions) in maintaining gametocyte structure and functioning has been systematized. MI and DCI improve the overall and progressive sperm motility by participating in signaling cascades downstream of reproductive hormone receptors (which normalizes androgen metabolism and helps prevent insulin resistance) and improving mitochondrial function. MI and DCI affect sperm maturation/functioning, motility and oocyte fertilization including those mediating inositol-dependent signaling protein phospholipase C-zeta (PLCz) and by modulating the electric fields of gametocytes. Clinical data on MI and DCI use in male infertility suggest an improved state of the zona pellucida, plasma membrane, cytoplasm and sperm reception. Manganese ions contribute to better gametocyte functioning by acting on testosterone concentration, increasing the activity of antioxidant enzymes and mitochondrial potential. Folates lowering gametotoxic homocysteine levels promote maintaining sperm DNA integrity. It is promising to prescribe MI/DCI in combination with organic manganese salts and folates to patients with idiopathic pathospermia, especially paralleled with carbohydrate metabolism disorders (insulin resistance) and reduced antioxidant protection.

Важным фактором вторичного мужского бесплодия является дефицит витаминов и микроэлементов. В настоящей работе систематизирован комплекс исследований миоинозитола (МИ), D-хироинозитола (ДХИ), их синергистов (фолаты, ионы марганца) в поддержании структуры и функционирования гамет. МИ и ДХИ улучшают общее количество подвижных и прогрессивно подвижных сперматозоидов посредством участия в сигнальных каскадах рецепторов репродуктивных гормонов (что нормализует обмен андрогенов и способствует профилактике инсулинорезистентности) и улучшения функции митохондрий. МИ и ДХИ оказывают воздействие на созревание/функционирование сперматозоидов, их подвижность и процесс оплодотворения ооцитов, в том числе с участием инозитол-зависимого сигнального белка фосфолипазы C-дзета (англ. phospholipase C-zeta, PLCz) и посредством модуляции электрических полей гамет. Клинические данные по использованию МИ и ДХИ при мужском бесплодии указывают на улучшение состояния zona pellucida, плазматической мембраны, цитоплазмы и рецепции сперматозоидов. Ионы марганца способствуют улучшению функционирования гаметоцитов посредством влияния на концентрацию тестостерона, повышения активности антиоксидантных ферментов и мембранного потенциала митохондрий. Фолаты, снижая уровни гаметотоксичного гомоцистеина, способствуют сохранению целостности ДНК сперматозоидов. Перспективно назначение МИ/ДХИ в сочетании с органическими солями марганца и фолатами пациентам с идиопатической патоспермией, особенно на фоне нарушений обмена углеводов (инсулинорезистентность) и сниженной антиоксидантной защиты.

бесплодиеинозитолымарганецфолатысперматозоидыгаметыinfertilityinositolsmanganesefolatesspermgerm cellsАвторы заявляют об отсутствии финансовой поддержкиThe authors declare no fundingReferencesDe Luca M.N., Colone M., Gambioli R. et al. Oxidative stress and male fertility: role of antioxidants and inositols. Antioxidants (Basel). 2021;10(8):1283. https://doi.org/10.3390/antiox10081283.De Luca M.N., Colone M., Gambioli R. et al. Oxidative stress and male fertility: role of antioxidants and inositols. Antioxidants (Basel). 2021;10(8):1283. https://doi.org/10.3390/antiox10081283.Etrusco A., Laganà A.S., Chiantera V. et al. Myo-inositol in assisted reproductive technology from bench to bedside. Trends Endocrinol Metab. 2024;35(1):74–83. https://doi.org/10.1016/j.tem.2023.09.005.Etrusco A., Laganà A.S., Chiantera V. et al. Myo-inositol in assisted reproductive technology from bench to bedside. Trends Endocrinol Metab. 2024;35(1):74–83. https://doi.org/10.1016/j.tem.2023.09.005.Carlomagno G., Nordio M., Chiu T.T., Unfer V. Contribution of myo-inositol and melatonin to human reproduction. Eur J Obstet Gynecol Reprod Biol. 2011;159(2):267–72. https://doi.org/10.1016/j.ejogrb.2011.07.038.Carlomagno G., Nordio M., Chiu T.T., Unfer V. Contribution of myo-inositol and melatonin to human reproduction. Eur J Obstet Gynecol Reprod Biol. 2011;159(2):267–72. https://doi.org/10.1016/j.ejogrb.2011.07.038.Colazingari S., Treglia M., Najjar R., Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet. 2013;288(6):1405–11. https://doi.org/10.1007/s00404-013-2855-3.Colazingari S., Treglia M., Najjar R., Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet. 2013;288(6):1405–11. https://doi.org/10.1007/s00404-013-2855-3.Lisi F., Carfagna P., Oliva M.M. et al. Pretreatment with myo-inositol in non-polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study. Reprod Biol Endocrinol. 2012;10:52. https://doi.org/10.1186/1477-7827-10-52.Lisi F., Carfagna P., Oliva M.M. et al. Pretreatment with myo-inositol in non-polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study. Reprod Biol Endocrinol. 2012;10:52. https://doi.org/10.1186/1477-7827-10-52.Chiu T.T., Rogers M.S., Briton-Jones C., Haines C. Effects of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod. 2003;18(2):408–16. https://doi.org/10.1093/humrep/deg113.Chiu T.T., Rogers M.S., Briton-Jones C., Haines C. Effects of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod. 2003;18(2):408–16. https://doi.org/10.1093/humrep/deg113.Chauvin T.R., Griswold M.D. Characterization of the expression and regulation of genes necessary for myo-inositol biosynthesis and transport in the seminiferous epithelium. Biol Reprod. 2004;70(3):744–51. https://doi.org/10.1095/biolreprod.103.022731.Chauvin T.R., Griswold M.D. Characterization of the expression and regulation of genes necessary for myo-inositol biosynthesis and transport in the seminiferous epithelium. Biol Reprod. 2004;70(3):744–51. https://doi.org/10.1095/biolreprod.103.022731.Hinton B.T., White R.W., Setchell B.P. Concentrations of myo-inositol in the luminal fluid of the mammalian testis and epididymis. J Reprod Fertil. 1980;58(2):395–9. https://doi.org/10.1530/jrf.0.0580395.Hinton B.T., White R.W., Setchell B.P. Concentrations of myo-inositol in the luminal fluid of the mammalian testis and epididymis. J Reprod Fertil. 1980;58(2):395–9. https://doi.org/10.1530/jrf.0.0580395.Громова О.А., Богачева Т.Е., Торшин И.Ю. и др. Метаболическое моделирование жировой болезни печени – фактора для проградиентного течения синдрома поликистозных яичников. Вопросы гинекологии, акушерства и перинатологии. 2025;24(1):120–31. https://doi.org/10.20953/1726-1678-2025-1-120-131.Gromova O.A., Bogacheva T.E., Torshin I.Yu. et al. Metabolic modeling of fatty liver disease – a factor for the progradient course of polycystic ovary syndrome. [Metabolicheskoe modelirovanie zhirovoj bolezni pecheni – faktora dlya progradientnogo techeniya sindroma polikistoznyh yaichnikov]. Voprosy ginekologii, akusherstva i perinatologii. 2025;24(1):120–31. (In Russ.). https://doi.org/10.20953/1726-1678-2025-1-120-131.Громова О.А., Торшин И.Ю., Тетруашвили Н.К. Перспективы применения экзогенных инозитолов для поддержания состояния кожи, волос и ногтей. Гинекология. 2022;24(4):261–70. https://doi.org/10.26442/20795696.2022.4.201824.Gromova O.A., Torshin I.Yu., Tetruashvili N.K. Prospects of exogenous inositols in maintaining of skin, hair and nails condition: a review. [Perspektivy primeneniya ekzogennyh inozitolov dlya podderzhaniya sostoyaniya kozhi, volos i nogtej]. Ginekologiya. 2022;24(4):261–70. (In Russ.). https://doi.org/10.26442/20795696.2022.4.201824.Condorelli R.A., Cannarella R., Crafa A. et al. Advances in non-hormonal pharmacotherapy for the treatment of male infertility: the role of inositols. Expert Opin Pharmacother. 2022;23(9):1081–90. https://doi.org/10.1080/14656566.2022.2060076.Condorelli R.A., Cannarella R., Crafa A. et al. Advances in non-hormonal pharmacotherapy for the treatment of male infertility: the role of inositols. Expert Opin Pharmacother. 2022;23(9):1081–90. https://doi.org/10.1080/14656566.2022.2060076.Niroomand M.J., Farahavar A., Aliarabi H., Yavari M. Ram semen response to сryopreservation with extender subjected to ultrasonic vibration and myo-inositol enrichment. Reprod Domest Anim. 2025;60(7):e70091. https://doi.org/10.1111/rda.70091.Niroomand M.J., Farahavar A., Aliarabi H., Yavari M. Ram semen response to сryopreservation with extender subjected to ultrasonic vibration and myo-inositol enrichment. Reprod Domest Anim. 2025;60(7):e70091. https://doi.org/10.1111/rda.70091.Dinicola S., Unfer V., Facchinetti F. et al. Inositols: from established knowledge to novel approaches. Int J Mol Sci. 2021;22(19):10575. https://doi.org/10.3390/ijms221910575.Dinicola S., Unfer V., Facchinetti F. et al. Inositols: from established knowledge to novel approaches. Int J Mol Sci. 2021;22(19):10575. https://doi.org/10.3390/ijms221910575.Condorelli R.A., La Vignera S., Di Bari F. et al. Effects of myoinositol on sperm mitochondrial function in-vitro. Eur Rev Med Pharmacol Sci. 2011;15(2):129–34.Condorelli R.A., La Vignera S., Di Bari F. et al. Effects of myoinositol on sperm mitochondrial function in-vitro. Eur Rev Med Pharmacol Sci. 2011;15(2):129–34.Condorelli R.A., La Vignera S., Bellanca S. et al. Myoinositol: does it improve sperm mitochondrial function and sperm motility? Urology. 2012;79(6):1290–5. https://doi.org/10.1016/j.urology.2012.03.005.Condorelli R.A., La Vignera S., Bellanca S. et al. Myoinositol: does it improve sperm mitochondrial function and sperm motility? Urology. 2012;79(6):1290–5. https://doi.org/10.1016/j.urology.2012.03.005.Riera M.F., Galardo M.N., Pellizzari E.H. et al. Participation of phosphatidyl inositol 3-kinase/protein kinase B and ERK1/2 pathways in interleukin-1beta stimulation of lactate production in Sertoli cells. Reproduction. 2007;133(4):763–73. https://doi.org/10.1530/rep.1.01091.Riera M.F., Galardo M.N., Pellizzari E.H. et al. Participation of phosphatidyl inositol 3-kinase/protein kinase B and ERK1/2 pathways in interleukin-1beta stimulation of lactate production in Sertoli cells. Reproduction. 2007;133(4):763–73. https://doi.org/10.1530/rep.1.01091.Bahat A., Eisenbach M. Human sperm thermotaxis is mediated by phospholipase C and inositol trisphosphate receptor Ca2+ channel. Biol Reprod. 2010;82(3):606–16. https://doi.org/10.1095/biolreprod.109.080127.Bahat A., Eisenbach M. Human sperm thermotaxis is mediated by phospho­lipase C and inositol trisphosphate receptor Ca2+ channel. Biol Reprod. 2010;82(3):606–16. https://doi.org/10.1095/biolreprod.109.080127 .Amdani S.N., Jones C., Coward K. Phospholipase C zeta (PLCζ): oocyte activation and clinical links to male factor infertility. Adv Biol Regul. 2013;53(3):292–308. https://doi.org/10.1016/j.jbior.2013.07.005.Amdani S.N., Jones C., Coward K. Phospholipase C zeta (PLCζ): oocyte activation and clinical links to male factor infertility. Adv Biol Regul. 2013;53(3):292–308. https://doi.org/10.1016/j.jbior.2013.07.005.Kashir J., Jones C., Lee H.C. et al. Loss of activity mutations in phospholipase C zeta (PLCζ) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes. Hum Reprod. 2011;26(12):3372–87. https://doi.org/10.1093/humrep/der336.Kashir J., Jones C., Lee H.C. et al. Loss of activity mutations in phospholipase C zeta (PLCζ) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes. Hum Reprod. 2011;26(12):3372–87. https://doi.org/10.1093/humrep/der336.Kuroda Y., Kaneko S., Yoshimura Y. et al. Are there inositol 1,4,5-triphosphate (IP3) receptors in human sperm? Life Sci. 1999;65(2):135–43. https://doi.org/10.1016/s0024-3205(99)00230-1.Kuroda Y., Kaneko S., Yoshimura Y. et al. Are there inositol 1,4,5-triphosphate (IP3) receptors in human sperm? Life Sci. 1999;65(2):135–43. https://doi.org/10.1016/s0024-3205(99)00230-1.Saunders C.M., Swann K., Lai F.A. ФЛС-ζeta, a sperm-specific PLC and its potential role in fertilization. Biochem Soc Symp. 2007;(74):23–36. https://doi.org/10.1042/BSS0740023.Saunders C.M., Swann K., Lai F.A. ФЛС-ζeta, a sperm-specific PLC and its potential role in fertilization. Biochem Soc Symp. 2007;(74):23–36. https://doi.org/10.1042/BSS0740023.Ickowicz D., Finkelstein M., Breitbart H. Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases. Asian J Androl. 2012;14(6):816–21. https://doi.org/10.1038/aja.2012.81.Ickowicz D., Finkelstein M., Breitbart H. Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases. Asian J Androl. 2012;14(6):816–21. https://doi.org/10.1038/aja.2012.81.Dumollard R., Marangos P., Fitzharris G. et al. Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production. Development. 2004;131(13):3057–67. https://doi.org/10.1242/dev.01181.Dumollard R., Marangos P., Fitzharris G. et al. Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production. Development. 2004;131(13):3057–67. https://doi.org/10.1242/dev.01181.Blackmore P.F. Extragenomic actions of progesterone in human sperm and progesterone metabolites in human platelets. Steroids. 1999;64(1–2):149–56. https://doi.org/10.1016/s0039-128x(98)00109-3.Blackmore P.F. Extragenomic actions of progesterone in human sperm and progesterone metabolites in human platelets. Steroids. 1999;64(1–2):149–56. https://doi.org/10.1016/s0039-128x(98)00109-3.Aquila S., Gentile M., Middea E. et al. Leptin secretion by human ejaculated spermatozoa. J Clin Endocrinol Metab. 2005;90(8):4753–61. https://doi.org/10.1210/jc.2004-2233.Aquila S., Gentile M., Middea E. et al. Leptin secretion by human ejaculated spermatozoa. J Clin Endocrinol Metab. 2005;90(8):4753–61. https://doi.org/10.1210/jc.2004-2233.Kawai T., Morioka S., Miyata H. et al. The significance of electrical signals in maturing spermatozoa for phosphoinositide regulation through voltage-sensing phosphatase. Nat Commun. 2024;15(1):7289. https://doi.org/10.1038/s41467-024-51755-2.Kawai T., Morioka S., Miyata H. et al. The significance of electrical signals in maturing spermatozoa for phosphoinositide regulation through voltage-sensing phosphatase. Nat Commun. 2024;15(1):7289. https://doi.org/10.1038/s41467-024-51755-2.Kooyman D.L., Byrne G.W., Logan J.S. Glycosyl phosphatidylinositol anchor. Exp Nephrol. 1998;6(2):148–51. https://doi.org/10.1159/000020516.Kooyman D.L., Byrne G.W., Logan J.S. Glycosyl phosphatidylinositol anchor. Exp Nephrol. 1998;6(2):148–51. https://doi.org/10.1159/000020516.Ueda Y., Yamaguchi R., Ikawa M. et al. PGAP1 knock-out mice show otocephaly and male infertility. J Biol Chem. 2007;282(42):30373–80. https://doi.org/10.1074/jbc.M705601200.Ueda Y., Yamaguchi R., Ikawa M. et al. PGAP1 knock-out mice show otocephaly and male infertility. J Biol Chem. 2007;282(42):30373–80. https://doi.org/10.1074/jbc.M705601200.Xue J., Guo Z. Convergent synthesis of a GPI containing an acylated inositol. J Am Chem Soc. 2003;125(52):16334–9. https://doi.org/10.1021/ja0382157.Xue J., Guo Z. Convergent synthesis of a GPI containing an acylated inositol. J Am Chem Soc. 2003;125(52):16334–9. https://doi.org/10.1021/ja0382157.Flori F., Giovampaola C.D., Focarelli R. et al. Epitope analysis of immunoglobulins against gp20, a GPI-anchored protein of the human sperm surface homologous to leukocyte antigen CD52. Tissue Antigens. 2005;66(3):209–16. https://doi.org/10.1111/j.1399-0039.2005.00463.x.Flori F., Giovampaola C.D., Focarelli R. et al. Epitope analysis of immunoglobulins against gp20, a GPI-anchored protein of the human sperm surface homologous to leukocyte antigen CD52. Tissue Antigens. 2005;66(3):209–16. https://doi.org/10.1111/j.1399-0039.2005.00463.x.Boerke A., van der Lit J., Lolicato F. et al. Removal of GPI-anchored membrane proteins causes clustering of lipid microdomains in the apical head area of porcine sperm. Theriogenology. 2014;81(4):613–24. https://doi.org/10.1016/j.theriogenology.2013.11.014.Boerke A., van der Lit J., Lolicato F. et al. Removal of GPI-anchored membrane proteins causes clustering of lipid microdomains in the apical head area of porcine sperm. Theriogenology. 2014;81(4):613–24. https://doi.org/10.1016/j.theriogenology.2013.11.014.Marcello M.R., Evans J.P. Multivariate analysis of male reproductive function in Inpp5b-/- mice reveals heterogeneity in defects in fertility, sperm-egg membrane interaction and proteolytic cleavage of sperm ADAMs. Mol Hum Reprod. 2010;16(7):492–505. https://doi.org/10.1093/molehr/gaq029.Marcello M.R., Evans J.P. Multivariate analysis of male reproductive function in Inpp5b-/- mice reveals heterogeneity in defects in fertility, sperm-egg membrane interaction and proteolytic cleavage of sperm ADAMs. Mol Hum Reprod. 2010;16(7):492–505. https://doi.org/10.1093/molehr/gaq029.Hellsten E., Evans J.P., Bernard D.J. et al. Disrupted sperm function and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b. Dev Biol. 2001;240(2):641–53. https://doi.org/10.1006/dbio.2001.0476.Hellsten E., Evans J.P., Bernard D.J. et al. Disrupted sperm function and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b. Dev Biol. 2001;240(2):641–53. https://doi.org/10.1006/dbio.2001.0476.Kiani M., Mehranjani M.S., Shariatzadeh M.A. Myoinositol improves sperm parameters in diabetic rats by reducing oxidative stress and regulating apoptosis-related genes. J Mol Histol. 2025;56(3):165. https://doi.org/10.1007/s10735-025-10451-1.Kiani M., Mehranjani M.S., Shariatzadeh M.A. Myoinositol improves sperm parameters in diabetic rats by reducing oxidative stress and regulating apoptosis-related genes. J Mol Histol. 2025;56(3):165. https://doi.org/10.1007/s10735-025-10451-1.Mendoza N., Galan M.I., Molina C. et al. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol. 2020;36(5):398–401. https://doi.org/10.1080/09513590.2019.1681959.Mendoza N., Galan M.I., Molina C. et al. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol. 2020;36(5):398–401. https://doi.org/10.1080/09513590.2019.1681959.Condorelli R.A., Barbagallo F., Calogero A.E. et al. D-chiro-inositol improves sperm mitochondrial membrane potential: in vitro evidence. J Clin Med. 2020;9(5):1373. https://doi.org/10.3390/jcm9051373.Condorelli R.A., Barbagallo F., Calogero A.E. et al. D-chiro-inositol improves sperm mitochondrial membrane potential: in vitro evidence. J Clin Med. 2020;9(5):1373. https://doi.org/10.3390/jcm9051373.Ghaemi M., Seighali N., Shafiee A. et al. The effect of myo-inositol on improving sperm quality and IVF outcomes: a systematic review and meta-analysis. Food Sci Nutr. 2024;12(11):8515–24. https://doi.org/10.1002/fsn3.4427.Ghaemi M., Seighali N., Shafiee A. et al. The effect of myo-inositol on improving sperm quality and IVF outcomes: a systematic review and meta-analysis. Food Sci Nutr. 2024;12(11):8515–24. https://doi.org/10.1002/fsn3.4427.Colone M., Marelli G., Unfer V. et al. Inositol activity in oligoasthenoteratospermia – an in vitro study. Eur Rev Med Pharmacol Sci. 2010;14(10):891–6.Colone M., Marelli G., Unfer V. et al. Inositol activity in oligoasthenoteratospermia – an in vitro study. Eur Rev Med Pharmacol Sci. 2010;14(10):891–6.Morabbi A., Karimian M. Trace and essential elements as vital components to improve the performance of the male reproductive system: Implications in cell signaling pathways. J Trace Elem Med Biol. 2024;83:127403. https://doi.org/10.1016/j.jtemb.2024.127403.Morabbi A., Karimian M. Trace and essential elements as vital components to improve the performance of the male reproductive system: Implications in cell signaling pathways. J Trace Elem Med Biol. 2024;83:127403. https://doi.org/10.1016/j.jtemb.2024.127403.Zhang B.L., Zhang Z.P., Shi S.M. et al. Dynamic elementomics of single-cell ICP-MS-derived signals in normal and calcium pump PMCA4-deficient mouse epididymal sperm during capacitation. Metallomics. 2023;15(10):mfad059. https://doi.org/10.1093/mtomcs/mfad059.Zhang B.L., Zhang Z.P., Shi S.M. et al. Dynamic elementomics of single-cell ICP-MS-derived signals in normal and calcium pump PMCA4-deficient mouse epididymal sperm during capacitation. Metallomics. 2023;15(10):mfad059. https://doi.org/10.1093/mtomcs/mfad059.Громова О.А., Андреева Е.Н., Торшин И.Ю. и др. Системно-биологический анализ ролей марганца в акушерстве и гинекологии: репродуктивное здоровье женщины, регуляция менструального цикла и профилактика пороков развития плода. Вопросы гинекологии, акушерства и перинатологии. 2020;19(1):103–13. https://doi.org/10.20953/1726-1678-2020-1-103-113.Gromova O.A., Andreeva E.N., Torshin I.Yu. et al. A systemic biological analysis of the role of manganese in obstetrics and gynaecology: women’s reproductive health, menstrual cycle regulation and prevention of fetal malformations. [Sistemno-biologicheskij analiz rolej marganca v akusherstve i ginekologii: reproduktivnoe zdorov'e zhenshchiny, regulyaciya menstrual'nogo cikla i profilaktika porokov razvitiya ploda]. Voprosy ginekologii, akusherstva i perinatologii. 2020;19(1):103–13. (In Russ.). https://doi.org/10.20953/1726-1678-2020-1-103-113.Lee B., Pine M., Johnson L. et al. Manganese acts centrally to activate reproductive hormone secretion and pubertal development in male rats. Reprod Toxicol. 2006;22(4):580–5. https://doi.org/10.1016/j.reprotox.2006.03.011.Lee B., Pine M., Johnson L. et al. Manganese acts centrally to activate reproductive hormone secretion and pubertal development in male rats. Reprod Toxicol. 2006;22(4):580–5. https://doi.org/10.1016/j.reprotox.2006.03.011.Zargari S., Towhidi A., Rezayazdi K., Kastelic J. Chemical form of trace minerals (copper, zinc and manganese) fed to rams affects plasma testosterone concentrations and semen characteristics. Reprod Domest Anim. 2025;60(8):e70115. https://doi.org/10.1111/rda.70115.Zargari S., Towhidi A., Rezayazdi K., Kastelic J. Chemical form of trace minerals (copper, zinc and manganese) fed to rams affects plasma testosterone concentrations and semen characteristics. Reprod Domest Anim. 2025;60(8):e70115. https://doi.org/10.1111/rda.70115.Sharan O., Stefanyk V., Bartlewski P.M., Sharan M. The effect of supplementing freezing extender with Mn2+-, Zn2+- or Cu2+-nanosuccinate on select post-thaw characteristics of ram semen. Reprod Biol. 2024;24(3):100932. https://doi.org/10.1016/j.repbio.2024.100932.Sharan O., Stefanyk V., Bartlewski P.M., Sharan M. The effect of supplementing freezing extender with Mn2+-, Zn2+- or Cu2+-nanosuccinate on select post-thaw characteristics of ram semen. Reprod Biol. 2024;24(3):100932. https://doi.org/10.1016/j.repbio.2024.100932.Reis L.S., Ramos A.A., Camargos A.S., Oba E. Effect of manganese supplementation on the membrane integrity and the mitochondrial potential of the sperm of grazing Nelore bulls. Anim Reprod Sci. 2014;150(1–2):1–6. https://doi.org/10.1016/j.anireprosci.2014.06.033.Reis L.S., Ramos A.A., Camargos A.S., Oba E. Effect of manganese supplementation on the membrane integrity and the mitochondrial potential of the sperm of grazing Nelore bulls. Anim Reprod Sci. 2014;150(1–2):1–6. https://doi.org/10.1016/j.anireprosci.2014.06.033.Ogawa S., Ota K., Takahashi T., Yoshida H. Impact of homocysteine as a preconceptional screening factor for in vitro fertilization and prevention of miscarriage with folic acid supplementation following frozen-thawed embryo transfer: a hospital-based retrospective cohort study. Nutrients. 2023;15(17):3730. https://doi.org/10.3390/nu15173730.Ogawa S., Ota K., Takahashi T., Yoshida H. Impact of homocysteine as a preconceptional screening factor for in vitro fertilization and prevention of miscarriage with folic acid supplementation following frozen-thawed embryo transfer: a hospital-based retrospective cohort study. Nutrients. 2023;15(17):3730. https://doi.org/10.3390/nu15173730.Demir K., Caliskan S.T., Celik S. et al. The effect of Folic Acid, B12, D, and E Vitamins and Melatonin levels in the follicular fluid taken by the Intracytoplasmic Sperm Injection method on pregnancy. Pak J Med Sci. 2024;40(3Part–II):433–7. https://doi.org/10.12669/pjms.40.3.7929.Demir K., Caliskan S.T., Celik S. et al. The effect of Folic Acid, B12, D, and E Vitamins and Melatonin levels in the follicular fluid taken by the Intracytoplasmic Sperm Injection method on pregnancy. Pak J Med Sci. 2024;40(3Part–II):433–7. https://doi.org/10.12669/pjms.40.3.7929.Ren H., Wang K., Liu Z. et al. Effect of low dietary folate on mouse spermatogenesis and spindle assembly checkpoint dysfunction may contribute to folate deficiency-induced chromosomal instability in cultured mouse spermatogonia. DNA Cell Biol. 2023;42(8):515–25. https://doi.org/10.1089/dna.2023.0035.Ren H., Wang K., Liu Z. et al. Effect of low dietary folate on mouse spermatogenesis and spindle assembly checkpoint dysfunction may contribute to folate deficiency-induced chromosomal instability in cultured mouse spermatogonia. DNA Cell Biol. 2023;42(8):515–25. https://doi.org/10.1089/dna.2023.0035.Rebolledo E.M.D., Chan D., Christensen K.E. et al. Sperm DNA methylation defects in a new mouse model of the 5,10-methylenetetrahydrofolate reductase 677C>T variant and correction with moderate dose folic acid supplementation. Mol Hum Reprod. 2024;30(4):gaae008. https://doi.org/10.1093/molehr/gaae008.Rebolledo E.M.D., Chan D., Christensen K.E. et al. Sperm DNA methylation defects in a new mouse model of the 5,10-methylenetetrahydrofolate reductase 677C>T variant and correction with moderate dose folic acid supplementation. Mol Hum Reprod. 2024;30(4):gaae008. https://doi.org/10.1093/molehr/gaae008.Mustari A., Alam M., Miah M.A. et al. Retrieval action of zinc and folic acid for the restoration of normal reproductive function in bisphenol – a exposed male albino mice. Vet Med (Praha). 2022;67(9):479–86. https://doi.org/10.17221/13/2022-VETMED.Mustari A., Alam M., Miah M.A. et al. Retrieval action of zinc and folic acid for the restoration of normal reproductive function in bisphenol – a exposed male albino mice. Vet Med (Praha). 2022;67(9):479–86. https://doi.org/10.17221/13/2022-VETMED.Toghan R., Amin Y.A., Ali R.A. et al. Protective effects of Folic acid against reproductive, hematological, hepatic, and renal toxicity induced by Acetamiprid in male Albino rats. Toxicology. 2022;469:153115. https://doi.org/10.1016/j.tox.2022.153115.Toghan R., Amin Y.A., Ali R.A. et al. Protective effects of Folic acid against reproductive, hematological, hepatic, and renal toxicity induced by Acetamiprid in male Albino rats. Toxicology. 2022;469:153115. https://doi.org/10.1016/j.tox.2022.153115.Торшин И.Ю., Громова О.А. Проблемы использования фенола (гидроксибензола) и парабенов в качестве стабилизаторов фармацевтических средств: анализ с применением методов машинного обучения. ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология. 2025;18(1):125–39. https://doi.org/10.17749/2070-4909/farmakoekonomika.2024.263.Torshin I.Yu., Gromova O.A. Problems of using phenol (hydroxybenzene) and parabens as pharmaceutical stabilizers: analysis using machine learning methods. [Problemy ispol'zovaniya fenola (gidroksibenzola) i parabenov v kachestve stabilizatorov farmacevticheskih sredstv: analiz s primeneniem metodov mashinnogo obucheniya]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2025;18(1):125–39. (In Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2024.263.Fadl A.M., Abdelnaby E.A., El-Sherbiny H.R. Supplemental dietary zinc sulphate and folic acid combination improves testicular volume and haemodynamics, testosterone levels and semen quality in rams under heat stress conditions. Reprod Domest Anim. 2022;57(6):567–76. https://doi.org/10.1111/rda.14096.Fadl A.M., Abdelnaby E.A., El-Sherbiny H.R. Supplemental dietary zinc sulphate and folic acid combination improves testicular volume and haemodynamics, testosterone levels and semen quality in rams under heat stress conditions. Reprod Domest Anim. 2022;57(6):567–76. https://doi.org/10.1111/rda.14096.Boushaba S., Helis Y., Lebaal R. et al. The relationship of sperm DNA integrity with serum vitamin levels (folate and cobalamin) and food consumption in infertile men. Clin Exp Reprod Med. 2023;50(1):53–62. https://doi.org/10.5653/cerm.2022.05736.Boushaba S., Helis Y., Lebaal R. et al. The relationship of sperm DNA integrity with serum vitamin levels (folate and cobalamin) and food consumption in infertile men. Clin Exp Reprod Med. 2023;50(1):53–62. https://doi.org/10.5653/cerm.2022.05736.Michaelsen M.P., Poulsen M., Bjerregaard A.A. et al. The effect of dietary supplements on male infertility in terms of pregnancy, live birth, and sperm parameters: a systematic review and meta-analysis. Nutrients. 2025;17(10):1710. https://doi.org/10.3390/nu17101710.Michaelsen M.P., Poulsen M., Bjerregaard A.A. et al. The effect of dietary supplements on male infertility in terms of pregnancy, live birth, and sperm parameters: a systematic review and meta-analysis. Nutrients. 2025;17(10):1710. https://doi.org/10.3390/nu17101710.Li X., Zeng Y.M., Luo Y.D. et al. Effects of folic acid and folic acid plus zinc supplements on the sperm characteristics and pregnancy outcomes of infertile men: a systematic review and meta-analysis. Heliyon. 2023;9(7):e18224. https://doi.org/10.1016/j.heliyon.2023.e18224.Li X., Zeng Y.M., Luo Y.D. et al. Effects of folic acid and folic acid plus zinc supplements on the sperm characteristics and pregnancy outcomes of infertile men: a systematic review and meta-analysis. Heliyon. 2023;9(7):e18224. https://doi.org/10.1016/j.heliyon.2023.e18224.Darbandi S., Darbandi M., Khorshid H.R.K., Sengupta P. Electrophysiology of human gametes: a systematic review. World J Mens Health. 2022;40(3):442–55. https://doi.org/10.5534/wjmh.210107.Darbandi S., Darbandi M., Khorshid H.R.K., Sengupta P. Electrophysiology of human gametes: a systematic review. World J Mens Health. 2022;40(3):442–55. https://doi.org/10.5534/wjmh.210107.

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