Immunological aspects of reproductive dysfunction in hypothalamic-pituitary dysfunction in young women (a literature review)

The article provides an overview of current data on the role of immune factors in the pathogenesis of reproductive disorders in hypothalamic-pituitary dysfunction in young women. The mechanisms of interaction between the hypothalamus, adipose tissue and the immune system are considered. It has been shown that obesity accompanying hypothalamic syndrome in 80% of cases induces chronic subclinical inflammation characterized by an imbalance of proinflammatory and anti-inflammatory cytokines, changes in the population composition of B-lymphocytes and macrophages of adipose tissue, hyperleptinemia and leptin resistance. A multilevel negative effect of immune disorders on the reproductive system is described: from suppression of GnRH secretion and impaired pituitary sensitivity to impaired folliculogenesis, decreased endometrial susceptibility and changes in immune tolerance. Special attention is paid to the age aspect – patients aged 18-25 years, in whom the effects of neuroimmunoendocrine disorders are most significant for the realization of reproductive function. A promising direction is the development of approaches to targeted modulation of the inflammatory response in order to restore fertility.

1. Bilbo S. D., Schwarz J. M. The immune system and developmental programming of brain and behavior. Frontiers in Neuroendocrinology. 2012 Aug; 33 (3): 267–286. doi: 10.1016/j.yfrne.2012.08.006.

2. Mishra S., Ashish A., Rai S. The Impact of Inflammatory Cytokines on Recurrent Pregnancy Loss: A Preliminary Investigation. Reproductive Sciences. 2025; 32: 804–814. doi: 10.1007/s43032-025-01786-x.

3. Randall T. D., Meza-Perez S. Immunity in adipose tissues: Cutting through the fat. Immunological Reviews. 2024 Jul; 324 (1): 4–10. doi: 10.1111/imr.13344.

4. Jiang Z., Tabuchi C., Gayer S. G., Bapat S. P. Immune Dysregulation in Obesity. Annual Reviews of Pathology. 2025 Jan; 20 (1): 483–509. doi: 10.1146/annurev-pathmechdis-051222-015350.

5. Valdearcos M., Douglass J. D., Robblee M. M., Dorfman M. D., Stifler D. R., Bennett M. L., Gerritse I., Fasnacht R., Barres B. A., Thaler J. P., Koliwad S. K. Microglial Inflammatory Signaling Orchestrates the Hypothalamic Immune Response to Dietary Excess and Mediates Obesity Susceptibility. Cell Metabolism. 2017 Jul 5; 26 (1): 185– 197.e3. DOI: 10.1016/j.cmet.2017.05.015.

6. Stasevich E. M., Zheremyan E. A., Kuprash D. V., Schwarz A. M. Interaction of adipocytes and B-lymphocytes in human metabolic diseases. Biokhimiya = Biochemistry. 2023; 88 (2): 335–344. doi: 10.31857/S0320972523020124 (In Russ.).

7. Srikakulapu P., McNamara C. A. B-lymphocytes and adipose tissue inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2020; 40: 1110–1122. doi: 10.1161/ATVBAHA.119.312467.

8. Svidinskaya E. A., Ageev M. B., Paleeva N. V., Mukhaeva V. A., Sosnova E. A. Menstrual dysfunction in adolescent girls who are overweight: a literature review. Arkhiv akusherstva i ginekologii im. V. F. Snegireva = V. F. Snegirev Archives of Obstetrics and Gynecology. 2022; 9 (2): 93–102. doi: 10.17816/2313-8726-2022-9-2-93-101 (In Russ.).

9. Ryzhov J. R., Shpakov A. O., Gzgzyan A. M. Leptin role in reproductive system regulation and its perspectives in assisted reproductive technologies. Problemy reproduktsii = Russian Journal of Human Reproduction. 2020; 26 (2): 53–61. doi: 10.17116/repro20202602153 (In Russ.).

10. Peredereeva E. V., Lushnikova A. A., Frykin A. D., Parokonnaya A. A. Leptin hormone and reproductive problems. Malignant Tumours. 2012; 2 (1): 35–39. doi: 10.18027/2224-5057-2012-1-35-39 (In Russ.).

11. Juan W., Ping G., Chunmei L., Meizhen P., Zhixiang D., Xian G. Correlation between leptin and IFN-γ involved in granulosa cellapoptosis in PCOS // Gynecological Endocrinology. 2020; 36. doi: 10.1080/09513590.2020.1760817.

12. Chaulin A. M., Grigorieva Yu. V. On the biological role of leptin. Scientific Review. Biological Sciences, 2021; 1: 32–38. doi: 10.17513/srbs.1222 (In Russ.).

13. Forsyth K. S., Jiwrajka N., Lovell C. D., Toothacre N. E., Anguera M. C. The conneXion between sex and immune responses. Nature Reviews Immunology. 2024 Jul; 24 (7): 487–502. doi: 10.1038/s41577-024-00996-9.

14. Hases L., Archer A., Williams C. ERβ and inflammation. Advances in experimental medicine and biology. 2022; 1390: 213–225. doi: 10.1007/978-3-031-11836-4_12.

15. Liu P., Zhang X., Hu J., Сui L., Zhao S., Jiao X., Qin Y. Dysregulated cytokine profile associated with biochemical premature ovarian insufficiency. American journal of reproductive immunology. 2020; 84 (4): e13292. doi: 10.1111/aji.13292.

16. Jiao X., Zhang X., Li N., Zhang D., Zhao S., Dang Y., Zanvit P., Jin W., Chen Z. J., Chen W., Qin Y. Treg deficiency-mediated TH 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells. Clinical and Translational Medicine. 2021 Jun; 11 (6): e448. doi: 10.1002/ctm2.448.

17. Absatarova Y. S., Evseeva Y. S., Andreeva E. N., Zuraeva Z. T., Sheremetyeva E. V., Grigoryan O. R., Mikheev R. K. Immunological status in patients with amenorrhea (literature review). Problemy endokrinologii = Problems of Endocrinology. 2024; 70 (6): 118–126. doi: 10.14341/probl13456 (In Russ.).

18. Chen Y., Wang R., Zhang N. and Xu L. The dual burden of obesity: decoding metabolism and female reproductive endocrinology. Frontiers in Physiology. 2025. 16: 1627607. doi: 10.3389/fphys.2025.1627607.