Expression of vascular endothelial growth factor a in the endometrium in uterine factor infertility

Aim. To assess the expression of vascular endothelial growth factor A for evaluating the functional state of the endometrium in women suffering from infertility and chronic endometritis.

Materials and methods. Endometrium biopsy specimens obtained from 41 patients with uterine factor infertility (experimental group) were examined. A comparison group was composed of 39 women diagnosed with the “male factor” infertility exhibiting no infl ammatory processes of the reproductive organs. An endometrial biopsy was performed in both phases of the menstrual cycle: on days 8–10 of the follicular phase and on days 21–24 of the luteal phase. The expression of vascular endothelial growth factor receptors was evaluated on the basis of immunohistochemical staining of the biopsy specimens using monoclonal antibodies. The results of the immunohistochemical reaction were quantifi ed using the ImageJ software. A quantitative criterion — a stained area coeffi cient (per cent) representing the ratio of the immunohistochemical staining area to that of a biopsy specimen — was proposed for assessing the level of VEGF-A expression.

Results. In the chronic endometritis group, the intensity of VEGF-A expression was found to be 1.4 times higher than that in the comparison group during the proliferation phase (p < 0.001). Expression values of the secretion phase were 1.9 times higher than those in the comparison group (p < 0.01).

Conclusion. Chronic endometritis is characterized by an overexpression of VEGF-A by various endometrium cellular components. Interpretation of immunohistochemical stains using the method of computer morphometry allows quantitative indicators characterizing the intensity of angiogenesis marker expression in the endometrium during the menstrual cycle to be obtained. The level of VEGF-A expression can be used as an additional marker improving the quality of biopsy diagnostics in patients with infertility. 

1. Uccelli A., Wolff T., Valente P., Di Maggio N., Pellegrino M., Gürke L., Banfi A., Gianni-Barrera R. Vascular endothelial growth factor biology for regenerative angiogenesis. Swiss. Med. Wkly. 2019; 149: w20011. DOI: 10.4414/smw.2019.20011

2. Bergantino F., Guariniello S., Raucci R., Colonna G., De Luca A., Normanno N., Costantini S. Structure-fluctuation-function relationships of seven pro-angiogenic isoforms of VEGFA, important mediators of tumorigenesis. Biochim. Biophys. Acta. 2015; 1854(5): 410–425. DOI: 10.1016/j.bbapap.2015.01.005

3. Nefedova N.A., Kharlova O.A., Danilova N.V., Malkov P.G., Gaifullin N.M. Markers of angiogenesis in tumor growth. Arkhiv Patologii. 2016; 2: 55–62 (In Russ., English abstract). DOI: 10.17116/patol201678255-62

4. Kellet E.P., Shurshalina A.V., Korneeva E.I. The role of endometrium in reproductive failures. Problemy Reproduktsii. 2010; 16(2): 16–20 (In Russ.).

5. Kozyreva E.V., Davidjan L.U., Kometova V.V. Chronic endometritis in the aspect of infertility and pregnancy loss. Ul’janovskij Mediko-Biologicheskij Zhurnal. 2017; 2: 56–62 (In Russ, English abstract). DOI: 10.23648/UMBJ.2017.26.6218

6. Cicinelli E., Matteo M., Trojano G., Mitola P.C., Tinelli R., Vitagliano A., Crupano F.M., Lepera A., Miragliotta G., Resta L. Chronic endometritis in patients with unexplained infertility: Prevalence and effects of antibiotic treatment on spontaneous conception. Am. J. Reprod. Immunol. 2018; 79(1): e12782. DOI: 10.1111/aji.12782

7. Krutova V.A., Chulkova A.М., Vanyan D.L., Chuprinenko L.M., Kasparyan R.A., Kopytko E.E., Dyakova T.G. Neoadjuvant diagnosis and management of chronic endometritis. Kubanskij Nauchnyj Medicinskij Vestnik. 2018; 25(1): 23–29 (In Russ., English abstract). DOI: 10.25207/1608-6228-2018-25-1-23-29

8. Su M.T., Lin S.H., Chen Y.C., Kuo P.L. Gene-gene interactions and gene polymorphisms of VEGF-A and EG-VEGF gene systems in recurrent pregnancy loss. J. Assist. Reprod, Genet. 2014; 31(6): 699–705. DOI: 10.1007/s10815-014-0223-2

9. Schneider C.A., Rasband W.S., Eliceiri K.W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods. 2012; 9(7): 671–675.

10. Kogan E.A., Demura T.A., Vodyanoy V.Y., Shurshalina A.V. Molecular and morphological aspects of endometrium receptivity malfunction in chronic endometritis. Arkhiv Patologii. 2012; 74(3): 15–27 (In Russ., English abstract).

11. Wu D., Kimura F., Zheng L., Ishida M., Niwa Y., Hirata K., Takebayashi A., Takashima A., Takahashi K., Kushima R., Zhang G., Murakami T. Chronic endometritis modifi es decidualization in human endometrial stromal cells. Reprod. Biol. Endocrinol. 2017; 15(1): 16–18. DOI 10.1186/s12958-017-0233-x

12. Likhacheva V.V., Zorina V.N., Tretyakova Y.N., Bazhenova L.G., Tretyakova T.V., Renge L.V. Current views on the chronic endometritis pathogenesis. Rossiiskiy Vestnik Akushera-Ginekologa. 2017; 4: 25–32 (In Russ., English abstract).

13. Kimura F., Takebayashi A., Ishida M., Nakamura A., Kitazawa J., Morimune A., Hirata K., Takahashi A., Tsuji S., Takashima A., Amano T., Tsuji S., Ono T., Kaku S., Kasahara K., Moritani S., Kushima R., Murakami T. Review: Chronic endometritis and its effect on reproduction. J. Obstet. Gynaecol. Res. 2019; 45(5): 951– 960. DOI: 10.1111/jog.13937

14. Kovalenko Y.A., Krutova V.A., Naumova N.V., Chuprinenko L.M. The effectiveness of in vitro fertilization and embryo transfer in women suffering from non-specific chronic endometritis. Kubanskij Nauchnyj Medicinskij Vestnik. 2017; (6): 59–64 (In Russ., English abstract). DOI: 10.25207/1608-6228-2017-24-6- 59-64