St-Cyr Sophie, Abuaish Sameera, Sivanathan Shathveekan, McGowan Patrick O
Department of Biological Sciences and Center for Environmental Epigenetics and Development, Department of Cell and Systems Biology, University of Toronto, Scarborough Campus, 1265 Military Trail, Toronto, ON, Canada.
Department of Biological Sciences and Center for Environmental Epigenetics and Development, Department of Cell and Systems Biology, University of Toronto, Scarborough Campus, 1265 Military Trail, Toronto, ON, Canada; Department of Psychology, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
Horm Behav. 2017 Aug;94:1-12. doi: 10.1016/j.yhbeh.2017.06.005. Epub 2017 Jun 20.
Prenatal stress mediated through the mother can lead to long-term adaptations in stress-related phenotypes in offspring. This study tested the long-lasting effect of prenatal exposure to predator odor, an ethologically relevant and psychogenic stressor, in the second half of pregnancy. As adults, the offspring of predator odor-exposed mothers showed increased anxiety-like behaviors in commonly used laboratory tasks assessing novelty-induced anxiety, increased defensive behavior in males and increased ACTH stress reactivity in females in response to predator odor. Female offspring from predator odor-exposed dams showed increased transcript abundance of glucocorticoid receptor (NR3C1) on the day of birth and FK506 binding protein 5 (FKBP5) in adulthood in the amygdala. The increase in FKBP5 expression was associated with decreased DNA methylation in Fkbp5 intron V. These results indicate a sex-specific response to maternal programming by prenatal predator odor exposure and a potential epigenetic mechanism linking these responses with modifications of the stress axis in females. These results are in accordance with the mismatch hypothesis stating that an animal's response to cues within its life history reflects environmental conditions anticipated during important developmental periods and should be adaptive when these conditions are concurring.
通过母亲介导的产前应激可导致后代与应激相关表型的长期适应性变化。本研究测试了孕期后半段暴露于捕食者气味（一种与行为学相关的心理应激源）的长期影响。成年后，暴露于捕食者气味的母亲的后代在评估新奇性诱导焦虑的常用实验室任务中表现出类似焦虑的行为增加，雄性的防御行为增加，雌性对捕食者气味的促肾上腺皮质激素应激反应性增加。暴露于捕食者气味的母鼠的雌性后代在出生当天杏仁核中糖皮质激素受体（NR3C1）的转录本丰度增加，成年后FK506结合蛋白5（FKBP5）增加。FKBP5表达的增加与Fkbp5内含子V中DNA甲基化的减少有关。这些结果表明，产前暴露于捕食者气味会导致对母体编程的性别特异性反应，以及一种潜在的表观遗传机制，将这些反应与雌性应激轴的改变联系起来。这些结果符合错配假说，即动物对其生命史中线索的反应反映了重要发育时期预期的环境条件，当这些条件一致时应该是适应性的。
