Morphological assessment of the ovarians after single and fractional local electron iradiation

Abstract

BACKGROUND: When malignant neoplasms of the pelvic organs are irradiated, healthy ovarian tissues can get into the irradiation area. So, among all physico-chemical factors, ionizing radiation is the most common cause of ovarian failure, which has a negative impact on fertility. Conducting research in this area is especially important in connection with the active introduction of electron therapy in the protocols for the treatment of malignant neoplasms of the small pelvis with the need to find ways to prevent and treat post-radiation ovarian lesions. In addition, one of the main tasks of modern radiobiology is the creation of experimental animal models in order to reveal the mechanisms of radiation exposure with subsequent extrapolation of the results obtained to humans in order to level the side effects of radiation therapy and select optimal doses.

AIM: The aim of the study was a morphofunctional assessment of the ovaries after local electron irradiation in single and fractional modes.

MATERIALS AND METHODS: Wistar rats (n = 30) were divided into three groups: I — control (n = 10); II (n = 10) — subjected to a single local irradiation with electrons at a dose of 2 Gy; III (n = 10) — subjected to fractional local irradiation with electrons in a total dose of 20 Gy.

RESULTS: After a single local irradiation with electrons at a dose of 2 Gy, multiple hemorrhages and a decrease in the number of growing follicles with a discontinuous theca layer, which were unevenly distributed over its volume, were noted in the ovary. A statistically significant difference in the number of follicles was revealed: a decrease in the number of primordial, primary, secondary and tertiary follicles and an increase in atretic follicles. The most pronounced difference in the number of follicles between the studied groups was found in the group of fractional electron irradiation at a dose of 20 Gy: the smallest number of primordial and the largest number of atretic follicles with signs of post-radiation fibrosis.

CONCLUSIONS: The most profound damage to the ovary develops after exposure to fractional electron irradiation at a total dose of 20 Gy compared with a single exposure to ionizing radiation at a dose of 2 Gy: a reduced number of follicles, a decrease in the area and thickness of the cortical substance, as well as the thickness of the ovarian tunica, in combination with the growth of the connective tissue.

Keywords

primordial follicles / oocyte / electron irradiation / ovarian reserve / ovarian failure

References

[1] Gerbi BJ, Antolak JA, Deibel FC, et al. Recommendations for clinical electron beam dosimetry: Supplement to the recommendations of Task Group 25. Med Phys. 2009;36(7):3239–3279. DOI: 10.1118/1.3125820

[2] Gerbi B.J., Antolak J.A., Deibel F.C. et al. Recommendations for clinical electron beam dosimetry: Supplement to the recommendations of Task Group 25 // Med. Phys. 2009. Vol. 36, No. 7. P. 3239–3279. DOI: 10.1118/1.3125820

[3] Reiser E, Bazzano MV, Solano ME, et al. Unlaid eggs: ovarian damage after low-dose radiation. Cells. 2022;11(7):1219. DOI: 10.3390/cells11071219

[4] Reiser E., Bazzano M.V., Solano M.E. et al. Unlaid eggs: ovarian damage after low-dose radiation // Cells. 2022. Vol. 11, No. 7. P. 1219. DOI: 10.3390/cells11071219

[5] Immediata V, Ronchetti C, Spadaro D, et al. Oxidative stress and human ovarian response-from somatic ovarian cells to oocytes damage: a clinical comprehensive narrative review. Antioxidants (Basel). 2022;11(7):1335. DOI: 10.3390/antiox11071335

[6] Immediata V., Ronchetti C., Spadaro D. et al. Oxidative stress and human ovarian response-from somatic ovarian cells to oocytes damage: a clinical comprehensive narrative review // Antioxidants (Basel). 2022. Vol. 11, No. 7. P. 1335. DOI: 10.3390/antiox11071335

[7] Citrin DE, Mitchell JB. Mechanisms of normal tissue injury from irradiation. Semin Radiat Oncol. 2017;27(4):316–324. DOI: 10.1016/j.semradonc.2017.04.001

[8] Citrin D.E., Mitchell J.B. Mechanisms of normal tissue injury from irradiation // Semin. Radiat. Oncol. 2017. Vol. 27, No. 4. P. 316–324. DOI: 10.1016/j.semradonc.2017.04.001

[9] Lee CJ, Yoon Y. Gamma-radiation-induced follicular degeneration in the prepubertal mouse ovary. Mutat Res. 2005;578(2):247–255. DOI: 10.1016/j.mrfmmm.2005.05.019

[10] Lee C.J., Yoon Y. Gamma-radiation-induced follicular degeneration in the prepubertal mouse ovary // Mutat. Res. 2005. Vol. 578. No. 2. P. 247–255. DOI: 10.1016/j.mrfmmm.2005.05.019

[11] Reisz JA, Bansal N, Qian J, et al. Effects of ionizing radiation on biological molecules — mechanisms of damage and emerging methods of detection. Antioxid Redox Signal. 2014;21(2):260–292. DOI: 10.1089/ars.2013.5489

[12] Reisz J.A., Bansal N., Qian J. et al. Effects of ionizing radiation on biological molecules — mechanisms of damage and emerging methods of detection // Antioxid. Redox Signal. 2014. Vol. 21, No. 2. P. 260–292. DOI: 10.1089/ars.2013.5489

[13] Boots C, Jungheim E. Inflammation and human ovarian follicular dynamics. Semin Reprod Med. 2015;33(4):270–275. DOI: 10.1055/s-0035-1554928

[14] Boots C., Jungheim E. Inflammation and human ovarian follicular dynamics // Semin. Reprod. Med. 2015. Vol. 33, No. 4. P. 270–275. DOI: 10.1055/s-0035-1554928

[15] Grover AR, Kimler BF, Duncan FE. Use of a small animal radiation research platform (SARRP) facilitates analysis of systemic versus targeted radiation effects in the mouse ovary. J Ovarian Res. 2018;11(1):72. DOI: 10.1186/s13048-018-0442-8

[16] Grover A.R., Kimler B.F., Duncan F.E. Use of a small animal radiation research platform (SARRP) facilitates analysis of systemic versus targeted radiation effects in the mouse ovary // J. Ovarian Res. 2018. Vol. 11, No. 1. P. 72. DOI: 10.1186/s13048-018-0442-8

[17] He L, Long X, Yu N, et al. Premature ovarian insufficiency (POI) induced by dynamic intensity modulated radiation therapy via P13K-AKT-FOXO3a in rat models. Biomed Res Int. 2021;2021:7273846. DOI: 10.1155/2021/7273846

[18] He L., Long X., Yu N. et al. Premature ovarian insufficiency (POI) induced by dynamic intensity modulated radiation therapy via P13K-AKT-FOXO3a in rat models // Biomed. Res. Int. 2021. Vol. 2021. P. 7273846. DOI: 10.1155/2021/7273846

[19] Tan R, He Y, Zhang S, et al. Effect of transcutaneous electrical acupoint stimulation on protecting against radiotherapy- induced ovarian damage in mice. J Ovarian Res. 2019;12(1):65. DOI: 10.1186/s13048-019-0541-1

[20] Tan R., He Y., Zhang S. et al. Effect of transcutaneous electrical acupoint stimulation on protecting against radiotherapy — induced ovarian damage in mice // J. Ovarian Res. 2019. Vol. 12, No. 1. P. 65. DOI: 10.1186/s13048-019-0541-1

[21] Oktem O, Kim SS, Selek U, et al. Ovarian and uterine functions in female survivors of childhood cancers. Oncologist. 2018;23(2):214–224. DOI: 10.1634/theoncologist.2017-0201

[22] Oktem O., Kim S.S., Selek U. et al. Ovarian and uterine functions in female survivors of childhood cancers // Oncologist. 2018. Vol. 23, No. 2. P. 214–224. DOI: 10.1634/theoncologist.2017-0201

[23] Gao W, Liang JX, Ma C, et al. The protective effect of N-Acetylcysteine on ionizing radiation induced ovarian failure and loss of ovarian reserve in female mouse. Biomed Res Int. 2017;2017:4176170. DOI: 10.1155/2017/4176170

[24] Gao W., Liang J.X., Ma C. et al. The protective effect of N-Acetylcysteine on ionizing radiation induced ovarian failure and loss of ovarian reserve in female mouse // Biomed. Res. Int. 2017. Vol. 2017. P. 4176170. DOI: 10.1155/2017/4176170

[25] Alesi LR, Nguyen QN, Stringer JM, et al. The future of fertility preservation for women treated with chemotherapy. Reprod Fertil. 2023;4(2):e220123. DOI: 10.1530/RAF-22-0123

[26] Alesi L.R., Nguyen Q.N., Stringer J.M. et al. The future of fertility preservation for women treated with chemotherapy // Reprod. Fertil. 2023. Vol. 4, No. 2. P. e220123. DOI: 10.1530/RAF-22-0123

[27] Zhang S, Liu Q, Chang M, et al. Chemotherapy impairs ovarian function through excessive ROS-induced ferroptosis. Cell Death Dis. 2023;14(5):340. DOI: 10.1038/s41419-023-05859-0

[28] Zhang S., Liu Q., Chang M. et al. Chemotherapy impairs ovarian function through excessive ROS-induced ferroptosis // Cell Death Dis. 2023. Vol. 14, No. 5. P. 340. DOI: 10.1038/s41419-023-05859-0

[29] Meirow D, Biederman H, Anderson RA, Wallace WH. Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol. 2010;53(4):727–739. DOI: 10.1097/GRF.0b013e3181f96b54

[30] Meirow D., Biederman H., Anderson R.A., Wallace W.H. Toxicity of chemotherapy and radiation on female reproduction // Clin. Obstet. Gynecol. 2010. Vol. 53, No. 4. P. 727–739. DOI: 10.1097/GRF.0b013e3181f96b54

[31] Taskin MI, Yay A, Adali E, et al. Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats. Gynecol Endocrinol. 2015;31(4):272–277. DOI: 10.3109/09513590.2014.984679

[32] Taskin M.I., Yay A., Adali E. et al. Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats // Gynecol. Endocrinol. 2015. Vol. 31, No. 4. P. 272–277. DOI: 10.3109/09513590.2014.984679

[33] Land KL, Miller FG, Fugate AC, Hannon PR. The effects of endocrine-disrupting chemicals on ovarian- and ovulation-related fertility outcomes. Mol Reprod Dev. 2022;89(12):608–631. DOI: 10.1002/mrd.23652

[34] Land K.L., Miller F.G., Fugate A.C., Hannon P.R. The effects of endocrine-disrupting chemicals on ovarian- and ovulation-related fertility outcomes // Mol. Reprod. Dev. 2022. Vol. 89, No. 12. P. 608–631. DOI: 10.1002/mrd.23652

[35] Kim S, Kim SW, Han SJ, et al. Molecular mechanism and prevention strategy of chemotherapy- and radiotherapy-induced ovarian damage. Int J Mol Sci. 2021;22(14):7484. DOI: 10.3390/ijms22147484

[36] Kim S., Kim S.W., Han S.J. et al. Molecular mechanism and prevention strategy of chemotherapy- and radiotherapy-induced ovarian damage // Int. J. Mol. Sci. 2021. Vol. 22, No. 14. P. 7484. DOI: 10.3390/ijms22147484

[37] Wei J, Wang B, Wang H, et al. Radiation-induced normal tissue damage: oxidative stress and epigenetic mechanisms. Oxid Med Cell Longev. 2019;2019:3010342. DOI: 10.1155/2019/3010342

[38] Wei J., Wang B., Wang H. et al. Radiation-induced normal tissue damage: oxidative stress and epigenetic mechanisms // Oxid. Med. Cell. Longev. 2019. Vol. 2019. P. 3010342. DOI: 10.1155/2019/3010342

[39] Wang W, Craig ZR, Basavarajappa MS, et al. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway. Toxicol Appl Pharmacol. 2012;258(2):288–295. DOI: 10.1016/j.taap.2011.11.008

[40] Wang W., Craig Z.R., Basavarajappa M.S. et al. Di (2-ethylhexyl phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway // Toxicol. Appl. Pharmacol. 2012. Vol. 258, No. 2. P. 288–295. DOI: 10.1016/j.taap.2011.11.008

[41] Yan F, Zhao Q, Li Y, et al. The role of oxidative stress in ovarian aging: a review. J Ovarian Res. 2022;15(1):100. DOI: 10.1186/s13048-022-01032-x

[42] Yan F., Zhao Q., Li Y. et al. The role of oxidative stress in ovarian aging: a review // J. Ovarian Res. 2022. Vol. 15, No. 1. P. 100. DOI: 10.1186/s13048-022-01032-x

[43] Rudnicka E, Kunicki M, Calik-Ksepka A, et al. Anti-müllerian hormone in pathogenesis, diagnostic and treatment of PCOS. Int J Mol Sci. 2021;22(22):12507. DOI: 10.3390/ijms222212507

[44] Rudnicka E., Kunicki M., Calik-Ksepka A. et al. Anti-müllerian hormone in pathogenesis, diagnostic and treatment of PCOS // Int. J. Mol. Sci. 2021. Vol. 22, No. 22. P. 12507. DOI: 10.3390/ijms222212507

[45] Chatziandreou E, Eustathiou A, Augoulea A, et al. Antimüllerian hormone as a tool to predict the age at menopause. Geriatrics (Basel). 2023;8(3):57. DOI: 10.3390/geriatrics8030057

[46] Chatziandreou E., Eustathiou A., Augoulea A. et al. Antimüllerian hormone as a tool to predict the age at menopause // Geriatrics (Basel). 2023. Vol. 8, No. 3. P. 57. DOI: 10.3390/geriatrics8030057

[47] Onder GO, Balcioglu E, Baran M, et al. The different doses of radiation therapy-induced damage to the ovarian environment in rats. Int J Radiat Biol. 2021;97(3):367–375. DOI: 10.1080/09553002.2021.1864497

[48] Onder G.O., Balcioglu E., Baran M. et al. The different doses of radiation therapy-induced damage to the ovarian environment in rats // Int. J. Radiat. Biol. 2021. Vol. 97, No. 3. P. 367–375. DOI: 10.1080/09553002.2021.1864497

RIGHTS & PERMISSIONS

Eco-Vector