Difference of oocyte radiosensitivity as a function of the follicle stage in a mouse model

• Published in: Reproductive biomedicine online
• Main Authors: Puy, Vincent, Barroca, Vilma, Messiaen, Sebastien, Menard, Veronique, Torres, Claire, Devanand, Caroline, Moison, Delphine, Lewandowski, Daniel, Martini, Emmanuelle, Frydman, Nelly, Livera, Gabriel
• Format: Journal Article
• Language: English
• Published: Elsevier 28-06-2021
• Subjects: Life Sciences; folliculogenesis; (3-5): fertility; oocyte; embryonic loss; radiation; (3-5): fertility folliculogenesis oocyte radiation embryonic loss
• ISSN: 1472-6483; 1472-6491

Objective. To study the effects of radiation on female fertility. Design. Experimental study of ovarian follicles radiosensitivity in a murine model. Setting. University Laboratory. Animals. NMRI and C57Bl6 mice. Interventions. To analyse ovarian follicle radiosensitivity, total body irradiation was performed on 8 days post-partum (dpp) mice with a single exposure to various doses (0.02; 0.1; 0.5; 2; 8 Gy) and type of radiation (X and ). We assessed fertility of irradiated (2 Gy) and sham treated mice by scoring pups after mating. Main outcome measures. Radiation effects were assessed by quantification of oocytes using histology, immunostaining and 3D approaches in ovaries of irradiated and sham treated mice. Fertility assessment was performed by counting the number of pups per mice and reporting the fetal abortion rate. Results. Primordial follicles (PF) were highly radiosensitive compared to growing follicles (GF) with a total loss observed from 0.5 Gy and onwards. We calculated a DL50 for PF equal to 47 mGy and 38 mGy for  and X-rays respectively. We show that PF oocytes are sensitive to radiation doses at least over 80 fold lower than doses killing GF (0.1 versus 8 Gy). Radiation exposure with 2 Gy induced the same quantity of DNA damage in both follicle populations. Surviving oocytes from GF were able to complete folliculogenesis similarly as sham treated mice. After mating, both the non-irradiated and the irradiated females sired a first litter. However, the rate of early fetal abortion was about 3 times higher in irradiated mothers compared to the non-irradiated ones. No more pups were obtained from irradiated females from further mating as the ovarian reserve was depleted in response to radiation. Conclusions. Both X and gamma radiations drastically reduced fertility lifespan and altered the quality of pregnancies. Our results emphasize the need for fertility preservation before radiation exposure and call for reassessing the use cryopreserved oocytes.