{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T23:05:13Z","timestamp":1769727913986,"version":"3.49.0"},"reference-count":60,"publisher":"Endocrinology Research Centre","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p>Neuroendocrine regulation of reproductive function represents a complex system based on the integration of signals between the central nervous system and peripheral organs. In recent years, particular attention has been given to the role of neuropeptides \u2014 such as kisspeptin, brain-derived neurotrophic factor (BDNF), and orexins \u2014 in the pathogenesis of disorders associated with menstrual irregularities. This review provides a detailed analysis of the molecular mechanisms underlying neuropeptide regulation in functional hypothalamic amenorrhea (FHA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS).<\/jats:p>\n                  <jats:p>Recent experimental studies are summarized, including stress-induced models of persistent estrous cycle arrest in laboratory animals and simulation of PCOS and POI using dietary and pharmacological interventions, respectively. Additionally, the review highlights publications demonstrating the significant role of impaired neuropeptide signaling in the development of reproductive disorders in women.<\/jats:p>\n                  <jats:p>The integration of fundamental research with clinical practice not only enhances our understanding of the pathophysiology of amenorrhea but also opens promising avenues for the development of novel therapeutic strategies, such as the use of kisspeptin agonists or other agents aimed at restoring reproductive function in women with various forms of menstrual dysfunction.<\/jats:p>","DOI":"10.14341\/probl13641","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:40:10Z","timestamp":1769686810000},"page":"100-109","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":0,"title":["Neuroendocrine regulation of the reproductive system: integration of research of neuropeptide and experimental pathophysiology of amenorrhea of different genesis (literature review)"],"prefix":"10.14341","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8189-1384","authenticated-orcid":true,"given":"Y. S.","family":"Evseeva","sequence":"first","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0696-5367","authenticated-orcid":true,"given":"Y. S.","family":"Absatarova","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8425-0020","authenticated-orcid":true,"given":"E. N.","family":"Andreeva","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre;\r\nRussian University of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9002-1662","authenticated-orcid":true,"given":"V. A.","family":"Ioutsi","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7418-0222","authenticated-orcid":true,"given":"S. A.","family":"Roumiantsev","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre;\r\nPirogov National Research Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7177-0254","authenticated-orcid":true,"given":"E. V.","family":"Sheremetyeva","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-7420","authenticated-orcid":true,"given":"O. R.","family":"Grigoryan","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-7877","authenticated-orcid":true,"given":"G. A.","family":"Melnichenko","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref1","unstructured":"https:\/\/rosstat.gov.ru\/free_doc\/new_site\/RPN22\/reports.html"},{"key":"ref2","unstructured":"Rossijskoe obshhestvo akusherov-ginekologov. Klinicheskie rekomendacii. Amenoreja. Moscow: Ministerstvo zdravoohranenija RF; 2021. (In Russ.)."},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Koysombat K, Tsoutsouki J, Patel AH, et al. Kisspeptin and neurokinin B: roles in reproductive health. Physiological reviews. 2025;105(2):707-764. doi: https:\/\/doi\/org\/10.1152\/physrev.00015.2024","DOI":"10.1152\/physrev.00015.2024"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"de Roux N, Genin E, Carel JC, et al. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(19):10972-10976. doi: https:\/\/doi\/org\/10.1073\/pnas.1834399100","DOI":"10.1073\/pnas.1834399100"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Roberts RE, Farahani L, Webber L, Jayasena C. Current understanding of hypothalamic amenorrhoea. Therapeutic advances in endocrinology and metabolism. 2020;11:2042018820945854. doi: https:\/\/doi\/org\/10.1177\/2042018820945854","DOI":"10.1177\/2042018820945854"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nature reviews. Endocrinology. 2018;14(5):270-284. doi: https:\/\/doi\/org\/10.1038\/nrendo.2018.24","DOI":"10.1038\/nrendo.2018.24"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Li M, Zhu Y, Wei J, et al. The global prevalence of premature ovarian insufficiency: a systematic review and meta-analysis. Climacteric.2023;26(2):95-102. doi: https:\/\/doi\/org\/10.1080\/13697137.2022.2153033","DOI":"10.1080\/13697137.2022.2153033"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Patel AH, Koysombat K, Pierret A, et al. Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential. Annals of the New York Academy of Sciences. 2024;1540(1):21-46. doi: https:\/\/doi\/org\/10.1111\/nyas.15220","DOI":"10.1111\/nyas.15220"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Chakravarthi VP, Khristi V, Ghosh S, et al. ESR2 is essential for gonadotropin-induced Kiss1 expression in granulosa cells. Endocrinology. 2018;159:3860\u201373. doi: https:\/\/doi\/org\/10.1210\/en.2018-00608","DOI":"10.1210\/en.2018-00608"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Chakravarthi VP, Ghosh S, Housami SM, et al. ER\u03b2 regulated ovarian kisspeptin plays an important role in oocyte maturation. Molecular and cellular endocrinology. 2021;527:111208. doi: https:\/\/doi\/org\/10.1016\/j.mce.2021.111208","DOI":"10.1016\/j.mce.2021.111208"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Ruohonen ST, Poutanen M, Tena-Sempere M. Role of kisspeptins in the control of the hypothalamic-pituitary-ovarian axis: old dogmas and new challenges. Fertility and sterility. 2020; 114:465\u201374. doi: https:\/\/doi\/org\/10.1016\/j.fertnstert.2020.06.038","DOI":"10.1016\/j.fertnstert.2020.06.038"},{"key":"ref12","unstructured":"\u0426\u0438\u0440\u043a\u0438\u043d \u0412.\u0418., \u0422\u0440\u0443\u0445\u0438\u043d\u0430 \u0421.\u0418., \u0422\u0440\u0443\u0445\u0438\u043d \u0410.\u041d. \u041e\u043a\u0441\u0438\u0442\u043e\u0446\u0438\u043d: \u0441\u0438\u043d\u0442\u0435\u0437, \u0432\u044b\u0434\u0435\u043b\u0435\u043d\u0438\u0435, \u043c\u0435\u0442\u0430\u0431\u043e\u043b\u0438\u0437\u043c \u0438 \u0440\u0435\u0433\u0443\u043b\u044f\u0446\u0438\u044f \u044d\u0442\u0438\u0445 \u043f\u0440\u043e\u0446\u0435\u0441\u0441\u043e\u0432 (\u043e\u0431\u0437\u043e\u0440). \/\/ \u0416\u0443\u0440\u043d\u0430\u043b \u043c\u0435\u0434\u0438\u043a\u043e-\u0431\u0438\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0439. \u2013 2018. \u2013 \u0422.6. \u2013 \u21163 \u2013 \u0421.270\u2013283. [Tsirkin VI, Trukhina SI, Trukhin A.N. Oksitotsin: sintez, vydelenie, metabolizm i regulyatsiya etikh protsessov (obzor) \/\/ Zhurnal mediko-biologicheskikh issledovanii. 2018;6(3):270-283. (in Russ.)] doi: https:\/\/doi\/org\/10.17238\/issn2542-1298.2018.6.3.270"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Matsui H, Asami T. Effects and therapeutic potentials of kisspeptin analogs: regulation of the hypothalamic-pituitarygonadal axis. Neuroendocrinology. 2014;99(1):49-60. doi: https:\/\/doi\/org\/10.1159\/000357809","DOI":"10.1159\/000357809"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Kotanidou S, Nikolettos N, Kritsotaki N, et al. Kisspeptins Regulating Fertility: Potential Future Therapeutic Approach in Infertility Treatment. Journal of clinical medicine. 2025;14(10):3284. doi: https:\/\/doi\/org\/10.3390\/jcm14103284","DOI":"10.3390\/jcm14103284"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Absatarova Yu.S., Evseeva Yu.S., Andreeva E.N., et al. Difficulties of differential diagnosis of functional hypothalamic amenorrhea and polycystic ovary syndrome: a systematic review. Problems of Endocrinology. 2025;71(1):83-91. (In Russ.) doi: https:\/\/doi\/org\/10.14341\/probl13529","DOI":"10.14341\/probl13529"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Podfigurna, A., Szeliga, A., & Meczekalski, B. Serum kisspeptin and corticotropin\u2010releasing hormone levels in patients with functional hypothalamic amenorrhea. Gynecological and Reproductive Endocrinology and Metabolism. 2020; 1(1), 37\u201342. doi: https:\/\/doi\/org\/10.53260\/grem.201017","DOI":"10.1007\/978-3-030-14358-9_3"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Podfigurna A, Maciejewska-Jeske M, Meczekalski B, Genazzani AD. Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea. Endocrine. 2020;70(3):635\u2013643. doi: https:\/\/doi\/org\/10.1007\/s12020-020-02481-4","DOI":"10.1007\/s12020-020-02481-4"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Szeliga A, Podfigurna A, Bala G, Meczekalski B. Decreased neurokinin B as a risk factor of functional hypothalamic amenorrhea. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. 2023;39(1):2216313. doi: https:\/\/doi\/org\/10.1080\/09513590.2023.2216313","DOI":"10.1080\/09513590.2023.2216313"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Ozawa H. Kisspeptin neurons as an integration center of reproductive regulation: Observation of reproductive function based on a new concept of reproductive regulatory nervous system. Reproductive medicine and biology. 2021;21(1):e12419. doi: https:\/\/doi\/org\/10.1002\/rmb2.12419","DOI":"10.1002\/rmb2.12419"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Yang JA, Song CI, Hughes JK, et al. Acute Psychosocial Stress Inhibits LH Pulsatility and Kiss1 Neuronal Activation in Female Mice. Endocrinology. 2017;158(11):3716-3723. doi: https:\/\/doi\/org\/10.1210\/en.2017-00301","DOI":"10.1210\/en.2017-00301"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Kinsey-Jones JS, Li XF, Knox AM, et al. Down-regulation of hypothalamic kisspeptin and its receptor, Kiss1r, mRNA expression is associated with stress-induced suppression of luteinising hormone secretion in the female rat. Journal of neuroendocrinology. 2009;21(1):20-29. doi: https:\/\/doi\/org\/10.1111\/j.1365-2826.2008.01807.x","DOI":"10.1111\/j.1365-2826.2008.01807.x"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Abdelkareem AO, Alotaibi FT, AlKusayer GM, et al. Immunoreactivity of Kisspeptin and Kisspeptin Receptor in Eutopic and Ectopic Endometrial Tissue of Women With and Without Endometriosis. Reproductive sciences (Thousand Oaks, Calif.). 2020;27(9):1731-1741. doi: https:\/\/doi\/org\/10.1007\/s43032-020-00167-w","DOI":"10.1007\/s43032-020-00167-w"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Abdelkareem AO, Gebril SM, AbdelHafez FF, et al. Kisspeptin and kisspeptin receptor immunoreactivity in euploid and aneuploid choriodecidual tissues of recurrent pregnancy losses. F&S science. 2023;4(1):56-64. doi: https:\/\/doi\/org\/10.1016\/j.xfss.2022.10.002","DOI":"10.1016\/j.xfss.2022.10.002"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Szeliga A, Rudnicka E, Maciejewska-Jeske M, et al. Neuroendocrine Determinants of Polycystic Ovary Syndrome. International journal of environmental research and public health. 2022;19(5):3089. doi: https:\/\/doi\/org\/10.3390\/ijerph19053089","DOI":"10.3390\/ijerph19053089"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Witchel SF, Tena-Sempere M. The Kiss1 system and polycystic ovary syndrome: lessons from physiology and putative pathophysiologic implications. Fertility and sterility. 2013;100(1):12-22. doi: https:\/\/doi\/org\/10.1016\/j.fertnstert.2013.05.024","DOI":"10.1016\/j.fertnstert.2013.05.024"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Varikasuvu SR, Prasad VS, Vamshika VC, et al. Circulatory metastin\/kisspeptin-1 in polycystic ovary syndrome: a systematic review and meta-analysis with diagnostic test accuracy. Reproductive biomedicine online. 2019;39(4):685-697. doi: https:\/\/doi\/org\/10.1016\/j.rbmo.2019.04.018","DOI":"10.1016\/j.rbmo.2019.04.018"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Akad M, Socolov R, Furnic\u0103 C, et al. Kisspeptin Variations in Patients with Polycystic Ovary Syndrome-A Prospective Case Control Study. Medicina (Kaunas, Lithuania). 2022;58(6):776. doi: https:\/\/doi\/org\/10.3390\/medicina58060776","DOI":"10.3390\/medicina58060776"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Ruohonen ST, Gaytan F, Usseglio Gaudi A, et al. Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure. Human reproduction (Oxford, England). 2022;37(4):806-821. doi: https:\/\/doi\/org\/10.1093\/humrep\/deab287","DOI":"10.1093\/humrep\/deab287"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Mattson MP, Duan W, Wan R, Guo Z. Prophylactic activation of neuroprotective stress response pathways by dietary and behavioral manipulations. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics. 2004;1(1):111-116. doi: https:\/\/doi\/org\/10.1602\/neurorx.1.1.111","DOI":"10.1602\/neurorx.1.1.111"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Wang X, Sun Z, Zhen J, Yu Q. Brain-derived neurotrophic factor from follicular fluid is positively associated with rate of mature ooocytes collected and cleavage rate in intracytoplasmic sperm injection patients. Journal of assisted reproduction and genetics. 2011;28(11):1053- 1058. doi: https:\/\/doi\/org\/10.1007\/s10815-011-9635-4","DOI":"10.1007\/s10815-011-9635-4"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Harel S, Jin S, Fisch B, et al. Tyrosine kinase B receptor and its activated neurotrophins in ovaries from human fetuses and adults. Molecular human reproduction. 2006;12(6):357-365. doi: https:\/\/doi\/org\/10.1093\/molehr\/gal033.","DOI":"10.1093\/molehr\/gal033"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Li C, Sui C, Wang W, et al. Baicalin Attenuates Oxygen-Glucose Deprivation\/Reoxygenation-Induced Injury by Modulating the BDNF-TrkB\/PI3K\/Akt and MAPK\/Erk1\/2 Signaling Axes in Neuron- Astrocyte Cocultures. Frontiers in pharmacology. 2021;12:599543. doi: https:\/\/doi\/org\/10.3389\/fphar.2021.599543","DOI":"10.3389\/fphar.2021.599543"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Qin X, Zhao Y, Zhang T, et al. TrkB agonist antibody ameliorates fertility deficits in aged and cyclophosphamide-induced premature ovarian failure model mice. Nature communications. 2022;13(1):914. doi: https:\/\/doi\/org\/10.1038\/s41467-022-28611-2","DOI":"10.1038\/s41467-022-28611-2"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Podfigurna-Stopa A, Casarosa E, Luisi M, et al. Decreased plasma concentrations of brain-derived neurotrophic factor (BDNF) in patients with functional hypothalamic amenorrhea [published correction appears in Gynecol Endocrinol. 2014 Jan;30(1):82]. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2013;29(9):817-820. doi: https:\/\/doi\/org\/10.3109\/09513590.2013.813472;","DOI":"10.3109\/09513590.2013.813472"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Begliuomini S, Casarosa E, Pluchino N, et al. Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor. Human reproduction (Oxford, England). 2007;22(4):995-1002. doi: https:\/\/doi\/org\/10.1093\/humrep\/del479","DOI":"10.1093\/humrep\/del479"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Drakopoulos P, Casarosa E, Bucci F, et al. Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea. Neuroendocrinology. 2015;101(3):256-262. doi: https:\/\/doi\/org\/10.1159\/000381456","DOI":"10.1159\/000381456"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Zhou J, Li C, Mi X, et al. BDNF secreted by mesenchymal stem cells improves aged oocyte quality and development potential by activating the ERK1\/2 pathway. Cell communication and signaling: CCS. 2025;23(1):150. doi: https:\/\/doi\/org\/10.1186\/s12964-025-02137-8","DOI":"10.1186\/s12964-025-02137-8"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Sha QQ, Dai XX, Dang Y, et al. A MAPK cascade couples maternal mRNA translation and degradation to meiotic cell cycle progression in mouse oocytes. Development (Cambridge, England). 2017;144(3):452-463. doi: https:\/\/doi\/org\/10.1242\/dev.144410","DOI":"10.1242\/dev.144410"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Kodomari I, Wada E, Nakamura S, Wada K. Maternal supply of BDNF to mouse fetal brain through the placenta. Neurochemistry international. 2009;54(2):95-98. doi: https:\/\/doi\/org\/10.1016\/j.neuint.2008.11.005","DOI":"10.1016\/j.neuint.2008.11.005"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Liu B, Liu Y, Li S, at al. Depletion of placental brain-derived neurotrophic factor (BDNF) is attributed to premature ovarian insufficiency (POI) in mice offspring. Journal of ovarian research. 2024;17(1):141. doi: https:\/\/doi\/org\/10.1186\/s13048-024-01467-4","DOI":"10.1186\/s13048-024-01467-4"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Czyzyk A, Filipowicz D, Podfigurna A, et al. Brain-derived neurotrophic factor (BDNF) plasma concentration in patients diagnosed with premature ovarian insufficiency (POI). Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. 2017;33(5):413-417. doi: https:\/\/doi\/org\/10.1080\/09513590.2017.1290073","DOI":"10.1080\/09513590.2017.1290073"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Nakabayashi M, Suzuki T, Takahashi K, et al. Orexin-A expression in human peripheral tissues. Molecular and cellular endocrinology. 2003;205(1-2):43-50. doi: https:\/\/doi\/org\/10.1016\/s0303-7207(03)00206-5","DOI":"10.1016\/S0303-7207(03)00206-5"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Yilmaz E, Celik O, Celik N, et al. Serum orexin-A (OXA) level decreases in polycystic ovarian syndrome. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2013;29(4):388-390. doi: https:\/\/doi\/org\/10.3109\/09513590.2012.754874","DOI":"10.3109\/09513590.2012.754874"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Absatarova Yu.S., Evseeva Yu.S., Andreeva E.N. Neuroendocrine features of the pathogenesis of polycystic ovary syndrome (literature review). Problems of Endocrinology. 2023;69(5):107-114. (In Russ.) doi: https:\/\/doi\/org\/10.14341\/probl13350","DOI":"10.14341\/probl13350"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Safdar M, Liang A, Rajput SA, et al. Orexin-A Regulates Follicular Growth, Proliferation, Cell Cycle and Apoptosis in Mouse Primary Granulosa Cells via the AKT\/ERK Signaling Pathway. Molecules (Basel, Switzerland). 2021;26(18):5635. doi: https:\/\/doi\/org\/10.3390\/molecules26185635","DOI":"10.3390\/molecules26185635"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Kim MR, Tilly JL. Current concepts in Bcl-2 family member regulation of female germ cell development and survival. Biochimica et biophysica acta. 2004;1644(2-3):205-210. doi: https:\/\/doi\/org\/10.1016\/j.bbamcr.2003.10.012","DOI":"10.1016\/j.bbamcr.2003.10.012"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Paulini F, Melo EO. The role of oocyte-secreted factors GDF9 and BMP15 in follicular development and oogenesis. Reproduction in domestic animals = Zuchthygiene. 2011;46(2):354-361. doi: https:\/\/doi\/org\/10.1111\/j.1439-0531.2010.01739.x","DOI":"10.1111\/j.1439-0531.2010.01739.x"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Gaytan F, Garcia-Galiano D, Dorfman MD, et al. Kisspeptin receptor haplo-insufficiency causes premature ovarian failure despite preserved gonadotropin secretion [published correction appears in Endocrinology. 2015 Sep;156(9):3402. doi: https:\/\/doi\/org\/10.1210\/en.2015-1591.]. Endocrinology. 2014;155(8):3088-3097. doi: https:\/\/doi\/org\/10.1210\/en.2014-1110","DOI":"10.1210\/en.2014-1110"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Velasco I, Franssen D, Daza-Due\u00f1as S, et al. Dissecting the KNDy hypothesis: KNDy neuron-derived kisspeptins are dispensable for puberty but essential for preserved female fertility and gonadotropin pulsatility. Metabolism. 2023;144:155556. doi: https:\/\/doi\/org\/10.1016\/j.metabol.2023.155556","DOI":"10.1016\/j.metabol.2023.155556"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Ahmed AI, Dowidar MF, Negm AF, et al. Bone marrow mesenchymal stem cells expressing Neat-1, Hotair-1, miR-21, miR-644, and miR-144 subsided cyclophosphamide-induced ovarian insufficiency by remodeling the IGF-1-kisspeptin system, ovarian apoptosis, and angiogenesis. Journal of ovarian research. 2024 Sep 12;17(1):184. doi: https:\/\/doi\/org\/10.1186\/s13048-024-01498-x. Erratum in: J Ovarian Res. 2024 Nov 29;17(1):239. doi: https:\/\/doi\/org\/10.1186\/s13048-024-01564-4.","DOI":"10.1186\/s13048-024-01564-4"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Gusev DV, Kuznetsov SY, Ivanets TY, Chernukha GE. Differential diagnosis of various forms of functional hypothalamic amenorrhea. Gynecology. 2019;21(4):14\u201318. (In Russ.) doi: https:\/\/doi\/org\/10.26442\/20795696.2019.3.190525","DOI":"10.26442\/20795696.2019.3.190525"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Frintrop L, Trinh S, Liesbrock J, et al. Establishment of a chronic activity-based anorexia rat model. Journal of neuroscience methods. 2018;293:191-198. doi: https:\/\/doi\/org\/10.1016\/j.jneumeth.2017.09.018","DOI":"10.1016\/j.jneumeth.2017.09.018"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Osuka S, Nakanishi N, Murase T, et al. Animal models of polycystic ovary syndrome: A review of hormone-induced rodent models focused on hypothalamus-pituitary-ovary axis and neuropeptides. Reproductive medicine and biology. 2018;18(2):151-160. doi: https:\/\/doi\/org\/10.1002\/rmb2.12262","DOI":"10.1002\/rmb2.12262"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Zhang H, Yi M, Zhang Y, et al. High-fat diets exaggerate endocrine and metabolic phenotypes in a rat model of DHEA-induced PCOS. Reproduction. 2016;151(4):431\u2013441. doi: https:\/\/doi\/org\/10.1530\/REP-15-0542.","DOI":"10.1530\/REP-15-0542"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Wang MX, Yin Q, Xu X. A Rat Model of Polycystic Ovary Syndrome with Insulin Resistance Induced by Letrozole Combined with High Fat Diet. Medical science monitor : international medical journal of experimental and clinical research. 2020;26:e922136. doi: https:\/\/doi\/org\/10.12659\/MSM.922136","DOI":"10.12659\/MSM.922136"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"Ryu Y, Kim SW, Kim YY, Ku SY. Animal models for human polycystic ovary syndrome (PCOS) focused on the use of indirect hormonal perturbations: a review of the literature. International journal of molecular sciences. 2019;20(11):2720\u20132720. doi: https:\/\/doi\/org\/10.3390\/ijms20112720.","DOI":"10.3390\/ijms20112720"},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"Wu S, Divall S, Nwaopara A, et al. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes. 2014;63(4):1270\u20131282. doi: https:\/\/doi\/org\/10.2337\/db13-1514.","DOI":"10.2337\/db13-1514"},{"key":"ref58","unstructured":"Mirseyyed SF, Zavareh S, Nasiri M, Hashemi-Moghaddam H. An Experimental Study on The Oxidative Status and Inflammatory Levels of A Rat Model of Polycystic Ovary Syndrome Induced by Letrozole and A New High-Fat Diet. International journal of fertility & sterility. 2023;18(1):45-53. doi: https:\/\/doi\/org\/10.22074\/ijfs.2023.1972296.1391"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"Li D, Jia Y, Hou Y, et al. Qilin Pill Exerts Therapeutic Effect on Resection-Induced Premature Ovarian Insufficiency Rats by Inhibiting the MAPK and PI3K-AKT Signaling Pathways. Drug design, development and therapy. 2021;15:3331-3345. doi: https:\/\/doi\/org\/10.2147\/DDDT.S321010","DOI":"10.2147\/DDDT.S321010"},{"key":"ref60","doi-asserted-by":"crossref","unstructured":"Lu G, Li HX, Song ZW, et al. Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy. Stem cell research & therapy. 2024;15(1):102. doi: https:\/\/doi\/org\/10.1186\/s13287-024-03709-0","DOI":"10.1186\/s13287-024-03709-0"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/13641\/10905","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:40:36Z","timestamp":1769686836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/13641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":60,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,12,2]]}},"URL":"https:\/\/doi.org\/10.14341\/probl13641","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"value":"2308-1430","type":"electronic"},{"value":"0375-9660","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}