Differential sensitivity of inbred mouse strains to ovarian damage in response to low-dose total body irradiation

• Published in: Biology of reproduction Vol. 102; no. 1; pp. 133 - 144
• Main Authors: Quan, Natalie, Harris, Lacey R, Halder, Ritika, Trinidad, Camille V, Johnson, Brian W, Horton, Shulamit, Kimler, Bruce F, Pritchard, Michele T, Duncan, Francesca E
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 12-02-2020; Oxford University Press
• Subjects: Animals; Female; Fertility; fertility preservation; follicle; Gene expression; Gene Expression - radiation effects; Hyaluronic Acid - metabolism; Mice, Inbred Strains; Osteopontin - genetics; Osteopontin - metabolism; ovarian reserve; Ovaries; ovary; Ovary - metabolism; Ovary - radiation effects; Physiological aspects; Radiation; Reproductive health; RESEARCH ARTICLE; Rodents; Species Specificity; Whole-Body Irradiation; United States; ovary; fertility preservation; ovarian reserve; radiation; follicle
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/ioz164

Radiation induces ovarian damage and accelerates reproductive aging. Inbred mouse strains exhibit differential sensitivity to lethality induced by total body irradiation (TBI), with the BALB/cAnNCrl (BALB/c) strain being more sensitive than the 129S2/SvPasCrl (129) strain. However, whether TBI-induced ovarian damage follows a similar pattern of strain sensitivity is unknown. To examine this possibility, female BALB/c and 129 mice were exposed to a single dose of 1 Gy (cesium-137 γ ) TBI at 5 weeks of age, and ovarian tissue was harvested for histological and gene expression analyses 2 weeks post exposure. Sham-treated mice served as controls. 1 Gy radiation nearly eradicated the primordial follicles and dramatically decreased the primary follicles in both strains. In contrast, larger growing follicles were less affected in the 129 relative to BALB/c strain. Although this TBI paradigm did not induce detectable ovarian fibrosis in either of the strains, we did observe strain-dependent changes in osteopontin (Spp1) expression, a gene involved in wound healing, inflammation, and fibrosis. Ovaries from BALB/c mice exhibited higher baseline Spp1 expression that underwent a significant decrease in response to radiation relative to ovaries from the 129 strain. A correspondingly greater change in the ovarian matrix, as evidenced by reduced ovarian hyaluronan content, was also observed following TBI in BALB/c mice relative to 129 mice. These early changes in the ovary may predispose BALB/c mice to more pronounced late effects of TBI. Taken together, our results demonstrate that aspects of ovarian damage mirror other organ systems with respect to overall strain-dependent radiation sensitivity. Summary sentence The ovarian response to low-dose total body radiation is mouse strain dependent.