Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
Cells. 2024 Jan 29;13(3):249. doi: 10.3390/cells13030249.
An adverse perinatal environment can increase long-term cancer risk, although the precise nature of associated perinatal triggers remain unknown. Sleep apnea is a common condition during pregnancy, characterized by recurrent cessations in breathing during sleep, and the potential consequences of sleep apnea during pregnancy as it relates to breast cancer risk in offspring have not been explored. To model sleep apnea, Sprague-Dawley dams were exposed during gestation to nightly intermittent hypoxia (GIH) or normoxia (GNx), and the mammary glands of female offspring were examined. GIH offspring demonstrated increased epithelial stem and progenitor cell populations, which are associated with diminished transforming growth factor beta (TGFβ) activity. Elevations in adipose tissue stem cells in the mammary gland were also identified in GIH offspring. In aging females, mammary tumors formed in GIH offspring. These tumors displayed a dramatic increase in stroma compared to tumors from GNx offspring, as well as distinct patterns of expression of stem cell-related pathways. Together, these results suggest that exposure to sleep apnea during pregnancy leads to lasting changes in the mammary glands of female offspring. Increased stem and progenitor cell populations as a result of GIH exposure could enhance long-term breast cancer risk, as well as alter the clinical behavior of resulting breast tumors.
不良的围产期环境会增加长期患癌风险，尽管相关围产期触发因素的确切性质仍不清楚。睡眠呼吸暂停是妊娠期间的常见病症，其特征是睡眠期间呼吸反复停止，而睡眠呼吸暂停在妊娠期间与后代乳腺癌风险之间的潜在后果尚未得到探索。为了模拟睡眠呼吸暂停，将 Sprague-Dawley 孕鼠暴露于夜间间歇性缺氧（GIH）或常氧（GNx）中，并检查雌性后代的乳腺。GIH 后代表现出上皮干细胞和祖细胞群体增加，这与转化生长因子 β（TGFβ）活性降低有关。还在 GIH 后代的乳腺中鉴定出脂肪组织干细胞的升高。在老年雌性中，GIH 后代形成了乳腺肿瘤。与来自 GNx 后代的肿瘤相比，这些肿瘤的基质明显增加，并且与干细胞相关途径的表达模式明显不同。总之，这些结果表明，妊娠期间暴露于睡眠呼吸暂停会导致雌性后代乳腺发生持久变化。由于 GIH 暴露导致的干细胞和祖细胞群体增加可能会增加长期患乳腺癌的风险，并改变由此产生的乳腺肿瘤的临床行为。
