Endometriosis is one of the leading causes of female infertility and is characterized by a complex polygenic and systemic pathogenesis, including impaired endothelial function, oxidative homeostasis, and chronic inflammation. It was established that the studied polymorphisms form a unified pathogenetic network with a synergistic effect on microcirculation, inflammation, and angiogenesis. The highest risk of developing endometriosis and infertility is associated with the triad combinations NOS3C–SOD2Val–IL6C and EDN1Asn–IL1BC–IL6C. In primary infertility, the endothelial-oxidative phenotype predominates, while in secondary infertility, the inflammatory-fibrous phenotype predominates. The obtained data confirm the significance of gene-gene interactions in the pathogenesis of endometriosis and substantiate the prospects for personalized prognosis and therapy.

Endometriosis, infertility, gene-gene interactions

Adamyan, L.V., Kulakov, V.I., Andreeva, E.N. Endometriosis: A Guide for Physicians. Moscow: Meditsina, 2016, 416 p.

Adamyan, L.V., Sonova, M.M., Sidorova, I.S. Endometriosis and Infertility: Modern Aspects of Diagnosis and Treatment. Obstetrics and Gynecology, 2018, no. 5, pp. 5–12.

Zaitseva, N.V., Unanyan, A.L., Kogan, E.A. Immunoinflammatory Mechanisms of Endometriosis. Problems of Reproduction, 2019, vol. 25, no. 2, pp. 45–52.

Sidorova, I.S., Unanyan, A.L., Kogan, E.A. Minimal forms of endometriosis: clinical and diagnostic difficulties // Russian Bulletin of Obstetrician-Gynecologist. - 2017. - Vol. 17, No. 2. - Pp. 25-31.

Unanyan A.L., Sidorova I.S., Kogan E.A. Pathogenetic mechanisms of endometriosis-associated infertility // Obstetrics, Gynecology and Reproduction. - 2020. - Vol. 14, No. 3. - Pp. 245-252.

Bulun S.E. Endometriosis // New England Journal of Medicine. - 2009. - Vol. 360, No. 3. - Pp. 268-279.

Burney R.O., Giudice L.C. Pathogenesis and pathophysiology of endometriosis // Fertility and Sterility. - 2012. - Vol. 98, No. 3. - P. 511–519.

Giudice L.C. Clinical practice. Endometriosis // New England Journal of Medicine. - 2010. - Vol. 362, No. 25. - P. 2389–2398.

Hapangama D.K., Turner M.A., Drury J.A. et al. Aberrant expression of endothelial nitric oxide synthase in endometriosis // Human Reproduction. - 2011. - Vol. 26, No. 4. - P. 956–964.

Harada T., Iwabe T., Terakawa N. Role of cytokines in endometriosis-associated infertility // Fertility and Sterility. - 2001. - Vol. 76, No. 1. - P. 1–10.

Ito F., Yamada Y., Shigemitsu A. et al. Role of oxidative stress in endometriosis-associated infertility // Reproductive Sciences. — 2013. — Vol. 20, No. 12. - P. 1444–1453.

Kim S.H., Choi Y.M., Chae H.D. et al. Association of NOS3 gene polymorphisms with endometriosis in Korean women // Fertility and Sterility. — 2014. — Vol. 101, No. 1. - P. 155–162.

Lousse J.C., Defrère S., Van Langendonckt A. et al. Endothelin-1 is overexpressed in endometriosis and promotes angiogenesis. Fertility and Sterility. - 2012. - Vol. 97, No. 3. - P. 701–707.

May K.E., Villar J., Kirtley S. et al. Endothelin-1 expression in endometriosis // Human Reproduction. - 2011. - Vol. 26, No. 4. - P. 921–929.

Santulli P., Borghese B., Chouzenoux S. et al. Serum and peritoneal oxidative stress markers in endometriosis // Human Reproduction. — 2015. — Vol. 30, No. 8. - P. 1910–1919.

Vodolazkaia A., Yesilyurt B.T., Kyama C.M. et al. Cytokines and endometriosis: from pathophysiology to diagnosis // Reproductive Biology and Endocrinology. - 2012. - Vol. 10. - P. 28.

Zondervan K.T., Becker C.M., Missmer S.A. Genetic insights into endometriosis // Nature Reviews Endocrinology. — 2018. — Vol. 14, No. 7. - P. 381–393.

Zondervan K.T., Becker C.M., Missmer S.A. Endometriosis // New England Journal of Medicine. — 2020. — Vol. 382, No. 13. - P. 1244–1256.