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. Epub 2021 Jan 6.

Abstract

Purpose: The sequelae of premature loss of ovarian function can undoubtedly have undesirable effects for a woman although radiotherapy is one of the most relevant treatment modalities for various types of malignancies. The aim of this study was to determine the effect of different doses of radiation on ovarian folliculogenesis, inflammation, and apoptotic markers.

Materials and methods: For this purpose, 40 healthy Wistar albino female rats divided into four groups: 1) Control group; 2) those that were exposed to total body 1 Gy of gamma rays; 3) those that were exposed to the total body 5 Gy of gamma rays, and 4) those that were exposed to total body 10 Gy of gamma rays. External irradiation to the total body was given with gamma irradiation delivered by the Co60 teletherapy machine. The day after radiation application the rats were sacrificed and the ovaries were removed in all groups. Histopathologic examination, follicle counting, and classification were performed in the ovarian tissues. The expression of AMH, TNF-α, IL1-β, Bax, and Bcl-2 was detected. The stained sections were examined for caspase 3 positive apoptotic cell numbers.

Results: The recorded results revealed that increased radiation dose induced obvious ovarian injuries that were indicated by histopathological, and immunohistochemical alterations, including elevation of ovarian injury markers. A significantly lower number of total and primordial follicles was detected with increasing radiation dose compared with the control group. According to our immunohistochemical results, 10 Gy of gamma rays group had the lowest AMH expression levels, while had the highest TNF-α, IL1-β expression level compared to the control group. When the groups were evaluated in terms of apoptosis, it was seen that the number of caspase 3 positive cells and Bax immunoreactivity intensity increased with radiation dose. In contrast, Bcl-2 immunoreactivity intensity decreased with increasing radiation dose compared with the control group.

Conclusions: We demonstrate here that dose rate plays an important role when estimating the relation between exposure to an increased dose of ionizing radiation and the risk of ovarian disease. According to these results, certain factors have to be optimized before introducing them into clinics.

Keywords: Radiation; apoptosis; ovary; pro-inflammatory cytokines.

MeSH terms

  • Animals
  • Anti-Mullerian Hormone / blood
  • Apoptosis
  • Dose-Response Relationship, Radiation
  • Female
  • Interleukin-1beta / analysis
  • Ovarian Follicle / pathology
  • Ovarian Follicle / radiation effects*
  • Radiotherapy Dosage
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Anti-Mullerian Hormone