Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
Biol Reprod. 2020 Feb 12;102(1):133-144. 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.
辐射会导致卵巢损伤并加速生殖衰老。近交系小鼠对全身照射（TBI）诱导的致死作用表现出不同的敏感性，BALB/cAnNCrl（BALB/c）品系比 129S2/SvPasCrl（129）品系更为敏感。然而，TBI 诱导的卵巢损伤是否遵循类似的品系敏感性模式尚不清楚。为了检验这种可能性，将 5 周龄雌性 BALB/c 和 129 小鼠暴露于 1 Gy（铯-137γ）TBI 单次剂量下，暴露后 2 周收获卵巢组织进行组织学和基因表达分析。假处理小鼠作为对照。1 Gy 辐射几乎根除了原始卵泡，并显著减少了两种品系的初级卵泡。相比之下，129 品系的较大生长卵泡受影响较小。尽管这种 TBI 范式在两种品系中均未诱导出可检测到的卵巢纤维化，但我们确实观察到了与品系相关的骨桥蛋白（Spp1）表达变化，该基因参与伤口愈合、炎症和纤维化。BALB/c 小鼠的卵巢表现出更高的基础 Spp1 表达，与 129 品系的卵巢相比，Spp1 表达在辐射后显著下降。在 BALB/c 小鼠中，TBI 后还观察到卵巢基质的相应更大变化，表现为卵巢透明质酸含量降低。BALB/c 小鼠的这些早期卵巢变化可能使它们更容易受到 TBI 的更明显的晚期影响。总之，我们的结果表明，卵巢损伤的某些方面与其他器官系统一样，与整体品系依赖性辐射敏感性有关。
