Материалы доступны только для специалистов сферы здравоохранения.
Чтобы посмотреть материал полностью
Авторизуйтесь
или зарегистрируйтесь.
Потенциальная роль эпигенетических факторов в развитии функциональной гипоталамической аменореи
Потенциальная роль эпигенетических факторов в развитии функциональной гипоталамической аменореи
Ермакова Д.М., Рахмонова Ф.С., Долгушина Н.В. Потенциальная роль эпигенетических факторов в развитии функциональной гипоталамической аменореи. Гинекология. 2026;28(1):43–47. DOI: 10.26442/20795696.2026.1.203566
________________________________________________
Материалы доступны только для специалистов сферы здравоохранения.
Чтобы посмотреть материал полностью
Авторизуйтесь
или зарегистрируйтесь.
Аннотация
Функциональная гипоталамическая аменорея (ФГА) – состояние, возникающее в результате нарушения работы гипоталамо-гипофизарно-яичниковой оси у женщин репродуктивного возраста под воздействием факторов внешней среды, многие из которых широко известны. При этом остаются неизученными факторы, обусловливающие индивидуальную предрасположенность к развитию этого заболевания, а также определяющие длительность и тяжесть его течения. Эпигенетические модификации, изменяющие активность работы генов без изменения структуры ДНК, рассматриваются как наиболее перспективные маркеры многих заболеваний, в том числе вовлекающих систему гипоталамус-гипофиз. Патогенетическая роль некодирующих РНК, одного из ключевых эпигенетических регуляторов в генезе этих заболеваний, активно изучается. Более того, исследуется возможность применения некодирующих РНК при ряде заболеваний в качестве терапевтического агента. Целью обзора стала систематизация данных литературы о потенциальной роли микроРНК как одного из наиболее активно изучаемых эпигенетических регуляторов в патогенезе ФГА. Описаны основные виды эпигенетических модификаций и актуальные данные об их роли в развитии заболеваний, вовлекающих систему гипоталамус-гипофиз, а также ассоциированных с ФГА состояний. Изучение роли эпигенетических регуляторов, изменяющих свою активность под действием внешних факторов, в развитии ФГА крайне перспективно. Более того, необходимы дальнейшие исследования, направленные на понимание возможности применения эпигенетических регуляторов в качестве терапевтических агентов у пациенток с таким заболеванием с целью повышения эффективности их лечения и минимизации негативных последствий заболевания для репродуктивного и соматического здоровья.
Ключевые слова: функциональная гипоталамическая аменорея, эпигеном, эпигенетические модификации, микроРНК
Keywords: functional hypothalamic amenorrhea, epigenome, epigenetic modifications, microRNA
Ключевые слова: функциональная гипоталамическая аменорея, эпигеном, эпигенетические модификации, микроРНК
________________________________________________
Keywords: functional hypothalamic amenorrhea, epigenome, epigenetic modifications, microRNA
Полный текст
Список литературы
1. Roberts RE, Farahani L, Webber L, Jayasena C. Current understanding of hypothalamic amenorrhoea. Ther Adv Endocrinol Metab. 2020;11:2042018820945854. DOI:10.1177/2042018820945854
2. Behary P, Comninos AN. Bone Perspectives in Functional Hypothalamic Amenorrhoea: An Update and Future Avenues. Front Endocrinol (Lausanne). 2022;13:923791. DOI:10.3389/fendo.2022.923791
3. Meczekalski B, Katulski K, Czyzyk A, et al. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest. 2014;37(11):1049-56. DOI:10.1007/s40618-014-0169-3
4. Bonazza F, Politi G, Leone D, et al. Psychological factors in functional hypothalamic amenorrhea: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:981491. DOI:10.3389/fendo.2023.981491
5. Perakakis N, Upadhyay J, Ghaly W, et al. Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function. Metabolism. 2018;85:240-9. DOI:10.1016/j.metabol.2018.05.003
6. Young J. Does Genetic Susceptibility of the Gonadotropic Axis Explain the Variable Impact of Stressors Causing Functional Hypothalamic Amenorrhea? J Clin Endocrinol Metab. 2021;106(3):e1473-5. DOI:10.1210/clinem/dgaa677
7. Щуко А.Г., Веселов А.А., Юрьева Т.Н., и др. Эпигенетика и способы ее реализации. Сибирский научный медицинский журнал. 2017;37(4):26-36 [Shchuko AG, Veselov AA, Yurieva TN, et al. Epigenetics and methods of its realization. Sibirskii Nauchnyi Meditsinskii Zhurnal. 2017;37(4):26-36 (in Russian)].
8. Holliday R. Mechanisms for the control of gene activity during development. Biol Rev Camb Philos Soc. 1990;65(4):431-71. DOI:10.1111/j.1469-185x.1990.tb01233.x
9. Klibaner-Schiff E, Simonin EM, Akdis CA, et al. Environmental exposures influence multigenerational epigenetic transmission. Clin Epigenetics. 2024;16(1):145. DOI:10.1186/s13148-024-01762-3
10. Neumann A, Sammallahti S, Cosin-Tomas M, et al. Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium. Genome Med. 2025;17(1):39. DOI:10.1186/s13073-025-01451-7
11. Kurian JR, Terasawa E. Epigenetic control of gonadotropin releasing hormone neurons. Front Endocrinol (Lausanne). 2013;4:61. DOI:10.3389/fendo.2013.00061
12. Gao L, Emperle M, Guo Y, et al. Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms. Nat Commun. 2020;11(1):3355. DOI:10.1038/s41467-020-17109-4
13. Papadogkonas G, Papamatheakis DA, Spilianakis C. 3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells. Front Immunol. 2022;13:921375. DOI:10.3389/fimmu.2022.921375
14. Fontana L, Garzia E, Marfia G, et al. Epigenetics of functional hypothalamic amenorrhea. Front Endocrinol (Lausanne). 2022;13:953431. DOI:10.3389/fendo.2022.953431
15. Derghal A, Djelloul M, Trouslard J, Mounien L. An Emerging Role of micro-RNA in the Effect of the Endocrine Disruptors. Front Neurosci. 2016;10:318. DOI:10.3389/fnins.2016.00318
16. Refael T, Melamed P. Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs. Endocrinology. 2021;162(8):bqab116. DOI:10.1210/endocr/bqab116
17. Iyer AK, Brayman MJ, Mellon PL. Dynamic chromatin modifications control GnRH gene expression during neuronal differentiation and protein kinase C signal transduction. Mol Endocrinol. 2011;25(3):460-73. DOI:10.1210/me.2010-0403
18. Borçoi AR, Mendes SO, Gasparini Dos Santos J, et al. Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association. J Psychiatr Res. 2020;121:24-30. DOI:10.1016/j.jpsychires.2019.10.011
19. Billah MM, Guo C, Mizuno K, et al. DNA methylation studies in mouse models of depression: a systematic review. Epigenomics. 2025;17(12):837-49. DOI:10.1080/17501911.2025.2525750
20. Miller O, Shakespeare-Finch J, Bruenig D, Mehta D. DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. Psychol Trauma. 2020;12(7):750-5. DOI:10.1037/tra0000574
21. Voisin S, Seale K, Jacques M, et al. Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle. Aging Cell. 2024;23(1):e13859. DOI:10.1111/acel.13859
22. Chambers J, Roscoe CMP, Chidley C, et al. Molecular Effects of Physical Activity and Body Composition: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2025;22(4):637. DOI:10.3390/ijerph22040637
23. Ding R, Su D, Zhao Q, et al. The role of microRNAs in depression. Front Pharmacol. 2023;14:1129186. DOI:10.3389/fphar.2023.1129186
24. de Souza PC, Warren Bezerra TP, de Oliveira ILR, et al. MicroRNAs in neuroplasticity: a comprehensive review of mechanisms and therapeutic strategies for neurodegenerative diseases. Neuroscience. 2025;585:97-106. DOI:10.1016/j.neuroscience.2025.08.034
25. Eiras MC, Pinheiro DP, Romcy KAM, et al. Polycystic Ovary Syndrome: the Epigenetics Behind the Disease. Reprod Sci. 2022;29(3):680-94. DOI:10.1007/s43032-021-00516-3
26. Li X, Qiu J, Liu H, et al. MicroRNA-33a negatively regulates myoblast proliferation by targeting IGF1, follistatin and cyclin D1. Biosci Rep. 2020;40(6):BSR20191327. DOI:10.1042/BSR20191327
27. de Toledo F, de Mendonça M, Martins AR, et al. MyomiRs as Markers of Insulin Resistance and Decreased Myogenesis in Skeletal Muscle of Diet-Induced Obese Mice. Front Endocrinol (Lausanne). 2016;7:76. DOI:10.3389/fendo.2016.00076
28. Ahmed K, LaPierre MP, Gasser E, et al. Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility. J Clin Invest. 2017;127(3):1061-74. DOI:10.1172/JCI90031
29. Wang CJ, Guo HX, Han DX, et al. Pituitary tissue-specific miR-7a-5p regulates FSH expression in rat anterior adenohypophyseal cells. PeerJ. 2019;7:e6458. DOI:10.7717/peerj.6458
30. Li L, Zhang J, Lu C, et al. MicroRNA-7a2 Contributes to Estrogen Synthesis and Is Modulated by FSH via the JNK Signaling Pathway in Ovarian Granulosa Cells. Int J Mol Sci. 2022;23(15):8565. DOI:10.3390/ijms23158565
31. Xian X, Cai LL, Li Y, et al. Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression. J Nanobiotechnology. 2022;20(1):122. DOI:10.1186/s12951-022-01332-w
32. Garaffo G, Conte D, Provero P, et al. The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system. Mol Cell Neurosci. 2015;68:103-19. DOI:10.1016/j.mcn.2015.04.007
33. Han DX, Sun XL, Xu MQ, et al. Roles of differential expression of microRNA-21-3p and microRNA-433 in FSH regulation in rat anterior pituitary cells. Oncotarget. 2017;8(22):36553-65. DOI:10.18632/oncotarget.16615
34. Fu X, Dong B, Tian Y, et al. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids. J Clin Invest. 2015;125(6):2497-509. DOI:10.1172/JCI75438
35. Xu H, Du X, Xu J, et al. Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function. PLoS Biol. 2020;18(2):e3000603. DOI:10.1371/journal.pbio.3000603
36. Li Y, Fan C, Wang L, et al. MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies. J Clin Invest. 2021;131(16):853. DOI:10.1172/JCI148853
37. Li X, Xiao J, Fan Y, et al. miR-29 family regulates the puberty onset mediated by a novel Gnrh1 transcription factor TBX21. J Endocrinol. 2019;242(3):185-97. DOI:10.1530/JOE-19-0082
38. Guo Y, Wu Y, Shi J, et al. miR-29a/b1 Regulates the Luteinizing Hormone Secretion and Affects Mouse Ovulation. Front Endocrinol (Lausanne). 2021;12:636220. DOI:10.3389/fendo.2021.636220
39. Trajkovski M, Hausser J, Soutschek J, et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 2011;474(7353):649-53. DOI:10.1038/nature10112
40. Fabová Z, Loncová B, Harrath AH, Sirotkin AV. Does the miR-105-1-Kisspeptin Axis Promote Ovarian Cell Functions? Reprod Sci. 2024;31(8):2293-308. DOI:10.1007/s43032-024-01554-3
41. Liu R, Wang M, Li E, et al. Dysregulation of microRNA-125a contributes to obesity-associated insulin resistance and dysregulates lipid metabolism in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(5):158640. DOI:10.1016/j.bbalip.2020.158640
42. Avendaño MS, Perdices-Lopez C, Guerrero-Ruiz Y, et al. The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin. Metabolism. 2024;157:155932. DOI:10.1016/j.metabol.2024.155932
43. van der Zee YY, Eijssen LMT, Mews P, et al. Blood miR-144-3p: a novel diagnostic and therapeutic tool for depression. Mol Psychiatry. 2022;27(11):4536-49. DOI:10.1038/s41380-022-01712-6
44. Fan C, Li Y, Lan T, et al. Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression. Mol Ther. 2022;30(3):1300-14. DOI:10.1016/j.ymthe.2021.11.006
45. Han DX, Xiao Y, Wang CJ, et al. Regulation of FSH expression by differentially expressed miR-186-5p in rat anterior adenohypophyseal cells. PLoS One. 2018;13(3):e0194300. DOI:10.1371/journal.pone.0194300
46. Li X, Xiao J, Li K, Zhou Y. MiR-199-3p modulates the onset of puberty in rodents probably by regulating the expression of Kiss1 via the p38 MAPK pathway. Mol Cell Endocrinol. 2020;518:110994. DOI:10.1016/j.mce.2020.110994
47. Hasuwa H, Ueda J, Ikawa M, Okabe M. miR-200b and miR-429 function in mouse ovulation and are essential for female fertility. Science. 2013;341(6141):71-3. DOI:10.1126/science.1237999
48. Ye RS, Li M, Li CY, et al. miR-361-3p regulates FSH by targeting FSHB in a porcine anterior pituitary cell model. Reproduction. 2017;153(3):341-9. DOI:10.1530/REP-16-0373
49. Li H, Li X, Zhang D, et al. MiR-375 potentially enhances GnRH expression by targeting Sp1 in GT1-7 cells. In Vitro Cell Dev Biol Anim. 2021;57(4):438-47. DOI:10.1007/s11626-020-00447-4
50. Wang HQ, Wang WH, Chen CZ, et al. Regulation of FSH Synthesis by Differentially Expressed miR-488 in Anterior Adenohypophyseal Cells. Animals (Basel). 2021;11(11):3262. DOI:10.3390/ani11113262
51. Zhou Y, Tong L, Wang M, et al. miR-505-3p is a repressor of puberty onset in female mice. J Endocrinol. 2019;240(3):379-92. DOI:10.1530/JOE-18-0533
52. Troppmann B, Kossack N, Nordhoff V, et al. MicroRNA miR-513a-3p acts as a co-regulator of luteinizing hormone/chorionic gonadotropin receptor gene expression in human granulosa cells. Mol Cell Endocrinol. 2014;390(1-2):65-72. DOI:10.1016/j.mce.2014.04.003
53. Song J, Luo S, Li SW. miRNA-592 is downregulated and may target LHCGR in polycystic ovary syndrome patients. Reprod Biol. 2015;15(4):229-37. DOI:10.1016/j.repbio.2015.10.005
54. Ju M, Yang L, Zhu J, et al. MiR-664-2 impacts pubertal development in a precocious-puberty rat model through targeting the NMDA receptor-1. Biol Reprod. 2019;100(6):1536-48. DOI:10.1093/biolre/ioz044
55. Dai T, Wei S, Li X, et al. A novel mechanism of kisspeptin regulating ovarian granulosa cell function via down-regulating let-7b to activate ERK/PI3K-Akt pathway in Tan sheep. Domest Anim Endocrinol. 2025;92:106947. DOI:10.1016/j.domaniend.2025.106947
2. Behary P, Comninos AN. Bone Perspectives in Functional Hypothalamic Amenorrhoea: An Update and Future Avenues. Front Endocrinol (Lausanne). 2022;13:923791. DOI:10.3389/fendo.2022.923791
3. Meczekalski B, Katulski K, Czyzyk A, et al. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest. 2014;37(11):1049-56. DOI:10.1007/s40618-014-0169-3
4. Bonazza F, Politi G, Leone D, et al. Psychological factors in functional hypothalamic amenorrhea: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:981491. DOI:10.3389/fendo.2023.981491
5. Perakakis N, Upadhyay J, Ghaly W, et al. Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function. Metabolism. 2018;85:240-9. DOI:10.1016/j.metabol.2018.05.003
6. Young J. Does Genetic Susceptibility of the Gonadotropic Axis Explain the Variable Impact of Stressors Causing Functional Hypothalamic Amenorrhea? J Clin Endocrinol Metab. 2021;106(3):e1473-5. DOI:10.1210/clinem/dgaa677
7. Shchuko AG, Veselov AA, Yurieva TN, et al. Epigenetics and methods of its realization. Sibirskii Nauchnyi Meditsinskii Zhurnal. 2017;37(4):26-36 (in Russian).
8. Holliday R. Mechanisms for the control of gene activity during development. Biol Rev Camb Philos Soc. 1990;65(4):431-71. DOI:10.1111/j.1469-185x.1990.tb01233.x
9. Klibaner-Schiff E, Simonin EM, Akdis CA, et al. Environmental exposures influence multigenerational epigenetic transmission. Clin Epigenetics. 2024;16(1):145. DOI:10.1186/s13148-024-01762-3
10. Neumann A, Sammallahti S, Cosin-Tomas M, et al. Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium. Genome Med. 2025;17(1):39. DOI:10.1186/s13073-025-01451-7
11. Kurian JR, Terasawa E. Epigenetic control of gonadotropin releasing hormone neurons. Front Endocrinol (Lausanne). 2013;4:61. DOI:10.3389/fendo.2013.00061
12. Gao L, Emperle M, Guo Y, et al. Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms. Nat Commun. 2020;11(1):3355. DOI:10.1038/s41467-020-17109-4
13. Papadogkonas G, Papamatheakis DA, Spilianakis C. 3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells. Front Immunol. 2022;13:921375. DOI:10.3389/fimmu.2022.921375
14. Fontana L, Garzia E, Marfia G, et al. Epigenetics of functional hypothalamic amenorrhea. Front Endocrinol (Lausanne). 2022;13:953431. DOI:10.3389/fendo.2022.953431
15. Derghal A, Djelloul M, Trouslard J, Mounien L. An Emerging Role of micro-RNA in the Effect of the Endocrine Disruptors. Front Neurosci. 2016;10:318. DOI:10.3389/fnins.2016.00318
16. Refael T, Melamed P. Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs. Endocrinology. 2021;162(8):bqab116. DOI:10.1210/endocr/bqab116
17. Iyer AK, Brayman MJ, Mellon PL. Dynamic chromatin modifications control GnRH gene expression during neuronal differentiation and protein kinase C signal transduction. Mol Endocrinol. 2011;25(3):460-73. DOI:10.1210/me.2010-0403
18. Borçoi AR, Mendes SO, Gasparini Dos Santos J, et al. Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association. J Psychiatr Res. 2020;121:24-30. DOI:10.1016/j.jpsychires.2019.10.011
19. Billah MM, Guo C, Mizuno K, et al. DNA methylation studies in mouse models of depression: a systematic review. Epigenomics. 2025;17(12):837-49. DOI:10.1080/17501911.2025.2525750
20. Miller O, Shakespeare-Finch J, Bruenig D, Mehta D. DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. Psychol Trauma. 2020;12(7):750-5. DOI:10.1037/tra0000574
21. Voisin S, Seale K, Jacques M, et al. Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle. Aging Cell. 2024;23(1):e13859. DOI:10.1111/acel.13859
22. Chambers J, Roscoe CMP, Chidley C, et al. Molecular Effects of Physical Activity and Body Composition: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2025;22(4):637. DOI:10.3390/ijerph22040637
23. Ding R, Su D, Zhao Q, et al. The role of microRNAs in depression. Front Pharmacol. 2023;14:1129186. DOI:10.3389/fphar.2023.1129186
24. de Souza PC, Warren Bezerra TP, de Oliveira ILR, et al. MicroRNAs in neuroplasticity: a comprehensive review of mechanisms and therapeutic strategies for neurodegenerative diseases. Neuroscience. 2025;585:97-106. DOI:10.1016/j.neuroscience.2025.08.034
25. Eiras MC, Pinheiro DP, Romcy KAM, et al. Polycystic Ovary Syndrome: the Epigenetics Behind the Disease. Reprod Sci. 2022;29(3):680-94. DOI:10.1007/s43032-021-00516-3
26. Li X, Qiu J, Liu H, et al. MicroRNA-33a negatively regulates myoblast proliferation by targeting IGF1, follistatin and cyclin D1. Biosci Rep. 2020;40(6):BSR20191327. DOI:10.1042/BSR20191327
27. de Toledo F, de Mendonça M, Martins AR, et al. MyomiRs as Markers of Insulin Resistance and Decreased Myogenesis in Skeletal Muscle of Diet-Induced Obese Mice. Front Endocrinol (Lausanne). 2016;7:76. DOI:10.3389/fendo.2016.00076
28. Ahmed K, LaPierre MP, Gasser E, et al. Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility. J Clin Invest. 2017;127(3):1061-74. DOI:10.1172/JCI90031
29. Wang CJ, Guo HX, Han DX, et al. Pituitary tissue-specific miR-7a-5p regulates FSH expression in rat anterior adenohypophyseal cells. PeerJ. 2019;7:e6458. DOI:10.7717/peerj.6458
30. Li L, Zhang J, Lu C, et al. MicroRNA-7a2 Contributes to Estrogen Synthesis and Is Modulated by FSH via the JNK Signaling Pathway in Ovarian Granulosa Cells. Int J Mol Sci. 2022;23(15):8565. DOI:10.3390/ijms23158565
31. Xian X, Cai LL, Li Y, et al. Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression. J Nanobiotechnology. 2022;20(1):122. DOI:10.1186/s12951-022-01332-w
32. Garaffo G, Conte D, Provero P, et al. The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system. Mol Cell Neurosci. 2015;68:103-19. DOI:10.1016/j.mcn.2015.04.007
33. Han DX, Sun XL, Xu MQ, et al. Roles of differential expression of microRNA-21-3p and microRNA-433 in FSH regulation in rat anterior pituitary cells. Oncotarget. 2017;8(22):36553-65. DOI:10.18632/oncotarget.16615
34. Fu X, Dong B, Tian Y, et al. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids. J Clin Invest. 2015;125(6):2497-509. DOI:10.1172/JCI75438
35. Xu H, Du X, Xu J, et al. Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function. PLoS Biol. 2020;18(2):e3000603. DOI:10.1371/journal.pbio.3000603
36. Li Y, Fan C, Wang L, et al. MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies. J Clin Invest. 2021;131(16):853. DOI:10.1172/JCI148853
37. Li X, Xiao J, Fan Y, et al. miR-29 family regulates the puberty onset mediated by a novel Gnrh1 transcription factor TBX21. J Endocrinol. 2019;242(3):185-97. DOI:10.1530/JOE-19-0082
38. Guo Y, Wu Y, Shi J, et al. miR-29a/b1 Regulates the Luteinizing Hormone Secretion and Affects Mouse Ovulation. Front Endocrinol (Lausanne). 2021;12:636220. DOI:10.3389/fendo.2021.636220
39. Trajkovski M, Hausser J, Soutschek J, et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 2011;474(7353):649-53. DOI:10.1038/nature10112
40. Fabová Z, Loncová B, Harrath AH, Sirotkin AV. Does the miR-105-1-Kisspeptin Axis Promote Ovarian Cell Functions? Reprod Sci. 2024;31(8):2293-308. DOI:10.1007/s43032-024-01554-3
41. Liu R, Wang M, Li E, et al. Dysregulation of microRNA-125a contributes to obesity-associated insulin resistance and dysregulates lipid metabolism in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(5):158640. DOI:10.1016/j.bbalip.2020.158640
42. Avendaño MS, Perdices-Lopez C, Guerrero-Ruiz Y, et al. The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin. Metabolism. 2024;157:155932. DOI:10.1016/j.metabol.2024.155932
43. van der Zee YY, Eijssen LMT, Mews P, et al. Blood miR-144-3p: a novel diagnostic and therapeutic tool for depression. Mol Psychiatry. 2022;27(11):4536-49. DOI:10.1038/s41380-022-01712-6
44. Fan C, Li Y, Lan T, et al. Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression. Mol Ther. 2022;30(3):1300-14. DOI:10.1016/j.ymthe.2021.11.006
45. Han DX, Xiao Y, Wang CJ, et al. Regulation of FSH expression by differentially expressed miR-186-5p in rat anterior adenohypophyseal cells. PLoS One. 2018;13(3):e0194300. DOI:10.1371/journal.pone.0194300
46. Li X, Xiao J, Li K, Zhou Y. MiR-199-3p modulates the onset of puberty in rodents probably by regulating the expression of Kiss1 via the p38 MAPK pathway. Mol Cell Endocrinol. 2020;518:110994. DOI:10.1016/j.mce.2020.110994
47. Hasuwa H, Ueda J, Ikawa M, Okabe M. miR-200b and miR-429 function in mouse ovulation and are essential for female fertility. Science. 2013;341(6141):71-3. DOI:10.1126/science.1237999
48. Ye RS, Li M, Li CY, et al. miR-361-3p regulates FSH by targeting FSHB in a porcine anterior pituitary cell model. Reproduction. 2017;153(3):341-9. DOI:10.1530/REP-16-0373
49. Li H, Li X, Zhang D, et al. MiR-375 potentially enhances GnRH expression by targeting Sp1 in GT1-7 cells. In Vitro Cell Dev Biol Anim. 2021;57(4):438-47. DOI:10.1007/s11626-020-00447-4
50. Wang HQ, Wang WH, Chen CZ, et al. Regulation of FSH Synthesis by Differentially Expressed miR-488 in Anterior Adenohypophyseal Cells. Animals (Basel). 2021;11(11):3262. DOI:10.3390/ani11113262
51. Zhou Y, Tong L, Wang M, et al. miR-505-3p is a repressor of puberty onset in female mice. J Endocrinol. 2019;240(3):379-92. DOI:10.1530/JOE-18-0533
52. Troppmann B, Kossack N, Nordhoff V, et al. MicroRNA miR-513a-3p acts as a co-regulator of luteinizing hormone/chorionic gonadotropin receptor gene expression in human granulosa cells. Mol Cell Endocrinol. 2014;390(1-2):65-72. DOI:10.1016/j.mce.2014.04.003
53. Song J, Luo S, Li SW. miRNA-592 is downregulated and may target LHCGR in polycystic ovary syndrome patients. Reprod Biol. 2015;15(4):229-37. DOI:10.1016/j.repbio.2015.10.005
54. Ju M, Yang L, Zhu J, et al. MiR-664-2 impacts pubertal development in a precocious-puberty rat model through targeting the NMDA receptor-1. Biol Reprod. 2019;100(6):1536-48. DOI:10.1093/biolre/ioz044
55. Dai T, Wei S, Li X, et al. A novel mechanism of kisspeptin regulating ovarian granulosa cell function via down-regulating let-7b to activate ERK/PI3K-Akt pathway in Tan sheep. Domest Anim Endocrinol. 2025;92:106947. DOI:10.1016/j.domaniend.2025.106947
2. Behary P, Comninos AN. Bone Perspectives in Functional Hypothalamic Amenorrhoea: An Update and Future Avenues. Front Endocrinol (Lausanne). 2022;13:923791. DOI:10.3389/fendo.2022.923791
3. Meczekalski B, Katulski K, Czyzyk A, et al. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest. 2014;37(11):1049-56. DOI:10.1007/s40618-014-0169-3
4. Bonazza F, Politi G, Leone D, et al. Psychological factors in functional hypothalamic amenorrhea: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:981491. DOI:10.3389/fendo.2023.981491
5. Perakakis N, Upadhyay J, Ghaly W, et al. Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function. Metabolism. 2018;85:240-9. DOI:10.1016/j.metabol.2018.05.003
6. Young J. Does Genetic Susceptibility of the Gonadotropic Axis Explain the Variable Impact of Stressors Causing Functional Hypothalamic Amenorrhea? J Clin Endocrinol Metab. 2021;106(3):e1473-5. DOI:10.1210/clinem/dgaa677
7. Щуко А.Г., Веселов А.А., Юрьева Т.Н., и др. Эпигенетика и способы ее реализации. Сибирский научный медицинский журнал. 2017;37(4):26-36 [Shchuko AG, Veselov AA, Yurieva TN, et al. Epigenetics and methods of its realization. Sibirskii Nauchnyi Meditsinskii Zhurnal. 2017;37(4):26-36 (in Russian)].
8. Holliday R. Mechanisms for the control of gene activity during development. Biol Rev Camb Philos Soc. 1990;65(4):431-71. DOI:10.1111/j.1469-185x.1990.tb01233.x
9. Klibaner-Schiff E, Simonin EM, Akdis CA, et al. Environmental exposures influence multigenerational epigenetic transmission. Clin Epigenetics. 2024;16(1):145. DOI:10.1186/s13148-024-01762-3
10. Neumann A, Sammallahti S, Cosin-Tomas M, et al. Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium. Genome Med. 2025;17(1):39. DOI:10.1186/s13073-025-01451-7
11. Kurian JR, Terasawa E. Epigenetic control of gonadotropin releasing hormone neurons. Front Endocrinol (Lausanne). 2013;4:61. DOI:10.3389/fendo.2013.00061
12. Gao L, Emperle M, Guo Y, et al. Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms. Nat Commun. 2020;11(1):3355. DOI:10.1038/s41467-020-17109-4
13. Papadogkonas G, Papamatheakis DA, Spilianakis C. 3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells. Front Immunol. 2022;13:921375. DOI:10.3389/fimmu.2022.921375
14. Fontana L, Garzia E, Marfia G, et al. Epigenetics of functional hypothalamic amenorrhea. Front Endocrinol (Lausanne). 2022;13:953431. DOI:10.3389/fendo.2022.953431
15. Derghal A, Djelloul M, Trouslard J, Mounien L. An Emerging Role of micro-RNA in the Effect of the Endocrine Disruptors. Front Neurosci. 2016;10:318. DOI:10.3389/fnins.2016.00318
16. Refael T, Melamed P. Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs. Endocrinology. 2021;162(8):bqab116. DOI:10.1210/endocr/bqab116
17. Iyer AK, Brayman MJ, Mellon PL. Dynamic chromatin modifications control GnRH gene expression during neuronal differentiation and protein kinase C signal transduction. Mol Endocrinol. 2011;25(3):460-73. DOI:10.1210/me.2010-0403
18. Borçoi AR, Mendes SO, Gasparini Dos Santos J, et al. Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association. J Psychiatr Res. 2020;121:24-30. DOI:10.1016/j.jpsychires.2019.10.011
19. Billah MM, Guo C, Mizuno K, et al. DNA methylation studies in mouse models of depression: a systematic review. Epigenomics. 2025;17(12):837-49. DOI:10.1080/17501911.2025.2525750
20. Miller O, Shakespeare-Finch J, Bruenig D, Mehta D. DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. Psychol Trauma. 2020;12(7):750-5. DOI:10.1037/tra0000574
21. Voisin S, Seale K, Jacques M, et al. Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle. Aging Cell. 2024;23(1):e13859. DOI:10.1111/acel.13859
22. Chambers J, Roscoe CMP, Chidley C, et al. Molecular Effects of Physical Activity and Body Composition: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2025;22(4):637. DOI:10.3390/ijerph22040637
23. Ding R, Su D, Zhao Q, et al. The role of microRNAs in depression. Front Pharmacol. 2023;14:1129186. DOI:10.3389/fphar.2023.1129186
24. de Souza PC, Warren Bezerra TP, de Oliveira ILR, et al. MicroRNAs in neuroplasticity: a comprehensive review of mechanisms and therapeutic strategies for neurodegenerative diseases. Neuroscience. 2025;585:97-106. DOI:10.1016/j.neuroscience.2025.08.034
25. Eiras MC, Pinheiro DP, Romcy KAM, et al. Polycystic Ovary Syndrome: the Epigenetics Behind the Disease. Reprod Sci. 2022;29(3):680-94. DOI:10.1007/s43032-021-00516-3
26. Li X, Qiu J, Liu H, et al. MicroRNA-33a negatively regulates myoblast proliferation by targeting IGF1, follistatin and cyclin D1. Biosci Rep. 2020;40(6):BSR20191327. DOI:10.1042/BSR20191327
27. de Toledo F, de Mendonça M, Martins AR, et al. MyomiRs as Markers of Insulin Resistance and Decreased Myogenesis in Skeletal Muscle of Diet-Induced Obese Mice. Front Endocrinol (Lausanne). 2016;7:76. DOI:10.3389/fendo.2016.00076
28. Ahmed K, LaPierre MP, Gasser E, et al. Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility. J Clin Invest. 2017;127(3):1061-74. DOI:10.1172/JCI90031
29. Wang CJ, Guo HX, Han DX, et al. Pituitary tissue-specific miR-7a-5p regulates FSH expression in rat anterior adenohypophyseal cells. PeerJ. 2019;7:e6458. DOI:10.7717/peerj.6458
30. Li L, Zhang J, Lu C, et al. MicroRNA-7a2 Contributes to Estrogen Synthesis and Is Modulated by FSH via the JNK Signaling Pathway in Ovarian Granulosa Cells. Int J Mol Sci. 2022;23(15):8565. DOI:10.3390/ijms23158565
31. Xian X, Cai LL, Li Y, et al. Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression. J Nanobiotechnology. 2022;20(1):122. DOI:10.1186/s12951-022-01332-w
32. Garaffo G, Conte D, Provero P, et al. The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system. Mol Cell Neurosci. 2015;68:103-19. DOI:10.1016/j.mcn.2015.04.007
33. Han DX, Sun XL, Xu MQ, et al. Roles of differential expression of microRNA-21-3p and microRNA-433 in FSH regulation in rat anterior pituitary cells. Oncotarget. 2017;8(22):36553-65. DOI:10.18632/oncotarget.16615
34. Fu X, Dong B, Tian Y, et al. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids. J Clin Invest. 2015;125(6):2497-509. DOI:10.1172/JCI75438
35. Xu H, Du X, Xu J, et al. Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function. PLoS Biol. 2020;18(2):e3000603. DOI:10.1371/journal.pbio.3000603
36. Li Y, Fan C, Wang L, et al. MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies. J Clin Invest. 2021;131(16):853. DOI:10.1172/JCI148853
37. Li X, Xiao J, Fan Y, et al. miR-29 family regulates the puberty onset mediated by a novel Gnrh1 transcription factor TBX21. J Endocrinol. 2019;242(3):185-97. DOI:10.1530/JOE-19-0082
38. Guo Y, Wu Y, Shi J, et al. miR-29a/b1 Regulates the Luteinizing Hormone Secretion and Affects Mouse Ovulation. Front Endocrinol (Lausanne). 2021;12:636220. DOI:10.3389/fendo.2021.636220
39. Trajkovski M, Hausser J, Soutschek J, et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 2011;474(7353):649-53. DOI:10.1038/nature10112
40. Fabová Z, Loncová B, Harrath AH, Sirotkin AV. Does the miR-105-1-Kisspeptin Axis Promote Ovarian Cell Functions? Reprod Sci. 2024;31(8):2293-308. DOI:10.1007/s43032-024-01554-3
41. Liu R, Wang M, Li E, et al. Dysregulation of microRNA-125a contributes to obesity-associated insulin resistance and dysregulates lipid metabolism in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(5):158640. DOI:10.1016/j.bbalip.2020.158640
42. Avendaño MS, Perdices-Lopez C, Guerrero-Ruiz Y, et al. The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin. Metabolism. 2024;157:155932. DOI:10.1016/j.metabol.2024.155932
43. van der Zee YY, Eijssen LMT, Mews P, et al. Blood miR-144-3p: a novel diagnostic and therapeutic tool for depression. Mol Psychiatry. 2022;27(11):4536-49. DOI:10.1038/s41380-022-01712-6
44. Fan C, Li Y, Lan T, et al. Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression. Mol Ther. 2022;30(3):1300-14. DOI:10.1016/j.ymthe.2021.11.006
45. Han DX, Xiao Y, Wang CJ, et al. Regulation of FSH expression by differentially expressed miR-186-5p in rat anterior adenohypophyseal cells. PLoS One. 2018;13(3):e0194300. DOI:10.1371/journal.pone.0194300
46. Li X, Xiao J, Li K, Zhou Y. MiR-199-3p modulates the onset of puberty in rodents probably by regulating the expression of Kiss1 via the p38 MAPK pathway. Mol Cell Endocrinol. 2020;518:110994. DOI:10.1016/j.mce.2020.110994
47. Hasuwa H, Ueda J, Ikawa M, Okabe M. miR-200b and miR-429 function in mouse ovulation and are essential for female fertility. Science. 2013;341(6141):71-3. DOI:10.1126/science.1237999
48. Ye RS, Li M, Li CY, et al. miR-361-3p regulates FSH by targeting FSHB in a porcine anterior pituitary cell model. Reproduction. 2017;153(3):341-9. DOI:10.1530/REP-16-0373
49. Li H, Li X, Zhang D, et al. MiR-375 potentially enhances GnRH expression by targeting Sp1 in GT1-7 cells. In Vitro Cell Dev Biol Anim. 2021;57(4):438-47. DOI:10.1007/s11626-020-00447-4
50. Wang HQ, Wang WH, Chen CZ, et al. Regulation of FSH Synthesis by Differentially Expressed miR-488 in Anterior Adenohypophyseal Cells. Animals (Basel). 2021;11(11):3262. DOI:10.3390/ani11113262
51. Zhou Y, Tong L, Wang M, et al. miR-505-3p is a repressor of puberty onset in female mice. J Endocrinol. 2019;240(3):379-92. DOI:10.1530/JOE-18-0533
52. Troppmann B, Kossack N, Nordhoff V, et al. MicroRNA miR-513a-3p acts as a co-regulator of luteinizing hormone/chorionic gonadotropin receptor gene expression in human granulosa cells. Mol Cell Endocrinol. 2014;390(1-2):65-72. DOI:10.1016/j.mce.2014.04.003
53. Song J, Luo S, Li SW. miRNA-592 is downregulated and may target LHCGR in polycystic ovary syndrome patients. Reprod Biol. 2015;15(4):229-37. DOI:10.1016/j.repbio.2015.10.005
54. Ju M, Yang L, Zhu J, et al. MiR-664-2 impacts pubertal development in a precocious-puberty rat model through targeting the NMDA receptor-1. Biol Reprod. 2019;100(6):1536-48. DOI:10.1093/biolre/ioz044
55. Dai T, Wei S, Li X, et al. A novel mechanism of kisspeptin regulating ovarian granulosa cell function via down-regulating let-7b to activate ERK/PI3K-Akt pathway in Tan sheep. Domest Anim Endocrinol. 2025;92:106947. DOI:10.1016/j.domaniend.2025.106947
________________________________________________
2. Behary P, Comninos AN. Bone Perspectives in Functional Hypothalamic Amenorrhoea: An Update and Future Avenues. Front Endocrinol (Lausanne). 2022;13:923791. DOI:10.3389/fendo.2022.923791
3. Meczekalski B, Katulski K, Czyzyk A, et al. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest. 2014;37(11):1049-56. DOI:10.1007/s40618-014-0169-3
4. Bonazza F, Politi G, Leone D, et al. Psychological factors in functional hypothalamic amenorrhea: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:981491. DOI:10.3389/fendo.2023.981491
5. Perakakis N, Upadhyay J, Ghaly W, et al. Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function. Metabolism. 2018;85:240-9. DOI:10.1016/j.metabol.2018.05.003
6. Young J. Does Genetic Susceptibility of the Gonadotropic Axis Explain the Variable Impact of Stressors Causing Functional Hypothalamic Amenorrhea? J Clin Endocrinol Metab. 2021;106(3):e1473-5. DOI:10.1210/clinem/dgaa677
7. Shchuko AG, Veselov AA, Yurieva TN, et al. Epigenetics and methods of its realization. Sibirskii Nauchnyi Meditsinskii Zhurnal. 2017;37(4):26-36 (in Russian).
8. Holliday R. Mechanisms for the control of gene activity during development. Biol Rev Camb Philos Soc. 1990;65(4):431-71. DOI:10.1111/j.1469-185x.1990.tb01233.x
9. Klibaner-Schiff E, Simonin EM, Akdis CA, et al. Environmental exposures influence multigenerational epigenetic transmission. Clin Epigenetics. 2024;16(1):145. DOI:10.1186/s13148-024-01762-3
10. Neumann A, Sammallahti S, Cosin-Tomas M, et al. Epigenetic timing effects on child developmental outcomes: a longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium. Genome Med. 2025;17(1):39. DOI:10.1186/s13073-025-01451-7
11. Kurian JR, Terasawa E. Epigenetic control of gonadotropin releasing hormone neurons. Front Endocrinol (Lausanne). 2013;4:61. DOI:10.3389/fendo.2013.00061
12. Gao L, Emperle M, Guo Y, et al. Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms. Nat Commun. 2020;11(1):3355. DOI:10.1038/s41467-020-17109-4
13. Papadogkonas G, Papamatheakis DA, Spilianakis C. 3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells. Front Immunol. 2022;13:921375. DOI:10.3389/fimmu.2022.921375
14. Fontana L, Garzia E, Marfia G, et al. Epigenetics of functional hypothalamic amenorrhea. Front Endocrinol (Lausanne). 2022;13:953431. DOI:10.3389/fendo.2022.953431
15. Derghal A, Djelloul M, Trouslard J, Mounien L. An Emerging Role of micro-RNA in the Effect of the Endocrine Disruptors. Front Neurosci. 2016;10:318. DOI:10.3389/fnins.2016.00318
16. Refael T, Melamed P. Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs. Endocrinology. 2021;162(8):bqab116. DOI:10.1210/endocr/bqab116
17. Iyer AK, Brayman MJ, Mellon PL. Dynamic chromatin modifications control GnRH gene expression during neuronal differentiation and protein kinase C signal transduction. Mol Endocrinol. 2011;25(3):460-73. DOI:10.1210/me.2010-0403
18. Borçoi AR, Mendes SO, Gasparini Dos Santos J, et al. Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association. J Psychiatr Res. 2020;121:24-30. DOI:10.1016/j.jpsychires.2019.10.011
19. Billah MM, Guo C, Mizuno K, et al. DNA methylation studies in mouse models of depression: a systematic review. Epigenomics. 2025;17(12):837-49. DOI:10.1080/17501911.2025.2525750
20. Miller O, Shakespeare-Finch J, Bruenig D, Mehta D. DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. Psychol Trauma. 2020;12(7):750-5. DOI:10.1037/tra0000574
21. Voisin S, Seale K, Jacques M, et al. Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle. Aging Cell. 2024;23(1):e13859. DOI:10.1111/acel.13859
22. Chambers J, Roscoe CMP, Chidley C, et al. Molecular Effects of Physical Activity and Body Composition: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2025;22(4):637. DOI:10.3390/ijerph22040637
23. Ding R, Su D, Zhao Q, et al. The role of microRNAs in depression. Front Pharmacol. 2023;14:1129186. DOI:10.3389/fphar.2023.1129186
24. de Souza PC, Warren Bezerra TP, de Oliveira ILR, et al. MicroRNAs in neuroplasticity: a comprehensive review of mechanisms and therapeutic strategies for neurodegenerative diseases. Neuroscience. 2025;585:97-106. DOI:10.1016/j.neuroscience.2025.08.034
25. Eiras MC, Pinheiro DP, Romcy KAM, et al. Polycystic Ovary Syndrome: the Epigenetics Behind the Disease. Reprod Sci. 2022;29(3):680-94. DOI:10.1007/s43032-021-00516-3
26. Li X, Qiu J, Liu H, et al. MicroRNA-33a negatively regulates myoblast proliferation by targeting IGF1, follistatin and cyclin D1. Biosci Rep. 2020;40(6):BSR20191327. DOI:10.1042/BSR20191327
27. de Toledo F, de Mendonça M, Martins AR, et al. MyomiRs as Markers of Insulin Resistance and Decreased Myogenesis in Skeletal Muscle of Diet-Induced Obese Mice. Front Endocrinol (Lausanne). 2016;7:76. DOI:10.3389/fendo.2016.00076
28. Ahmed K, LaPierre MP, Gasser E, et al. Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility. J Clin Invest. 2017;127(3):1061-74. DOI:10.1172/JCI90031
29. Wang CJ, Guo HX, Han DX, et al. Pituitary tissue-specific miR-7a-5p regulates FSH expression in rat anterior adenohypophyseal cells. PeerJ. 2019;7:e6458. DOI:10.7717/peerj.6458
30. Li L, Zhang J, Lu C, et al. MicroRNA-7a2 Contributes to Estrogen Synthesis and Is Modulated by FSH via the JNK Signaling Pathway in Ovarian Granulosa Cells. Int J Mol Sci. 2022;23(15):8565. DOI:10.3390/ijms23158565
31. Xian X, Cai LL, Li Y, et al. Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression. J Nanobiotechnology. 2022;20(1):122. DOI:10.1186/s12951-022-01332-w
32. Garaffo G, Conte D, Provero P, et al. The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system. Mol Cell Neurosci. 2015;68:103-19. DOI:10.1016/j.mcn.2015.04.007
33. Han DX, Sun XL, Xu MQ, et al. Roles of differential expression of microRNA-21-3p and microRNA-433 in FSH regulation in rat anterior pituitary cells. Oncotarget. 2017;8(22):36553-65. DOI:10.18632/oncotarget.16615
34. Fu X, Dong B, Tian Y, et al. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids. J Clin Invest. 2015;125(6):2497-509. DOI:10.1172/JCI75438
35. Xu H, Du X, Xu J, et al. Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function. PLoS Biol. 2020;18(2):e3000603. DOI:10.1371/journal.pbio.3000603
36. Li Y, Fan C, Wang L, et al. MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies. J Clin Invest. 2021;131(16):853. DOI:10.1172/JCI148853
37. Li X, Xiao J, Fan Y, et al. miR-29 family regulates the puberty onset mediated by a novel Gnrh1 transcription factor TBX21. J Endocrinol. 2019;242(3):185-97. DOI:10.1530/JOE-19-0082
38. Guo Y, Wu Y, Shi J, et al. miR-29a/b1 Regulates the Luteinizing Hormone Secretion and Affects Mouse Ovulation. Front Endocrinol (Lausanne). 2021;12:636220. DOI:10.3389/fendo.2021.636220
39. Trajkovski M, Hausser J, Soutschek J, et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 2011;474(7353):649-53. DOI:10.1038/nature10112
40. Fabová Z, Loncová B, Harrath AH, Sirotkin AV. Does the miR-105-1-Kisspeptin Axis Promote Ovarian Cell Functions? Reprod Sci. 2024;31(8):2293-308. DOI:10.1007/s43032-024-01554-3
41. Liu R, Wang M, Li E, et al. Dysregulation of microRNA-125a contributes to obesity-associated insulin resistance and dysregulates lipid metabolism in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(5):158640. DOI:10.1016/j.bbalip.2020.158640
42. Avendaño MS, Perdices-Lopez C, Guerrero-Ruiz Y, et al. The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin. Metabolism. 2024;157:155932. DOI:10.1016/j.metabol.2024.155932
43. van der Zee YY, Eijssen LMT, Mews P, et al. Blood miR-144-3p: a novel diagnostic and therapeutic tool for depression. Mol Psychiatry. 2022;27(11):4536-49. DOI:10.1038/s41380-022-01712-6
44. Fan C, Li Y, Lan T, et al. Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression. Mol Ther. 2022;30(3):1300-14. DOI:10.1016/j.ymthe.2021.11.006
45. Han DX, Xiao Y, Wang CJ, et al. Regulation of FSH expression by differentially expressed miR-186-5p in rat anterior adenohypophyseal cells. PLoS One. 2018;13(3):e0194300. DOI:10.1371/journal.pone.0194300
46. Li X, Xiao J, Li K, Zhou Y. MiR-199-3p modulates the onset of puberty in rodents probably by regulating the expression of Kiss1 via the p38 MAPK pathway. Mol Cell Endocrinol. 2020;518:110994. DOI:10.1016/j.mce.2020.110994
47. Hasuwa H, Ueda J, Ikawa M, Okabe M. miR-200b and miR-429 function in mouse ovulation and are essential for female fertility. Science. 2013;341(6141):71-3. DOI:10.1126/science.1237999
48. Ye RS, Li M, Li CY, et al. miR-361-3p regulates FSH by targeting FSHB in a porcine anterior pituitary cell model. Reproduction. 2017;153(3):341-9. DOI:10.1530/REP-16-0373
49. Li H, Li X, Zhang D, et al. MiR-375 potentially enhances GnRH expression by targeting Sp1 in GT1-7 cells. In Vitro Cell Dev Biol Anim. 2021;57(4):438-47. DOI:10.1007/s11626-020-00447-4
50. Wang HQ, Wang WH, Chen CZ, et al. Regulation of FSH Synthesis by Differentially Expressed miR-488 in Anterior Adenohypophyseal Cells. Animals (Basel). 2021;11(11):3262. DOI:10.3390/ani11113262
51. Zhou Y, Tong L, Wang M, et al. miR-505-3p is a repressor of puberty onset in female mice. J Endocrinol. 2019;240(3):379-92. DOI:10.1530/JOE-18-0533
52. Troppmann B, Kossack N, Nordhoff V, et al. MicroRNA miR-513a-3p acts as a co-regulator of luteinizing hormone/chorionic gonadotropin receptor gene expression in human granulosa cells. Mol Cell Endocrinol. 2014;390(1-2):65-72. DOI:10.1016/j.mce.2014.04.003
53. Song J, Luo S, Li SW. miRNA-592 is downregulated and may target LHCGR in polycystic ovary syndrome patients. Reprod Biol. 2015;15(4):229-37. DOI:10.1016/j.repbio.2015.10.005
54. Ju M, Yang L, Zhu J, et al. MiR-664-2 impacts pubertal development in a precocious-puberty rat model through targeting the NMDA receptor-1. Biol Reprod. 2019;100(6):1536-48. DOI:10.1093/biolre/ioz044
55. Dai T, Wei S, Li X, et al. A novel mechanism of kisspeptin regulating ovarian granulosa cell function via down-regulating let-7b to activate ERK/PI3K-Akt pathway in Tan sheep. Domest Anim Endocrinol. 2025;92:106947. DOI:10.1016/j.domaniend.2025.106947
Авторы
Д.М. Ермакова, Ф.С. Рахмонова*, Н.В. Долгушина
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России, Москва, Российская Федерация
*f_rakhmonova@oparina4.ru
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation
*f_rakhmonova@oparina4.ru
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России, Москва, Российская Федерация
*f_rakhmonova@oparina4.ru
________________________________________________
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation
*f_rakhmonova@oparina4.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.