（圖片來自網絡）

　　越來越多證據表明DNA並不是親代將遺傳信息傳遞到子代的唯一方式。親代在一生當中經曆的許多事件都會對遺傳信息的傳遞產生影響。

　　最近，來自賓夕法尼亞大學的研究人員在國際學術期刊PNAS上發表了一項最新研究進展，他們在分子水平上發現了應激如何改變雄性小鼠的精子，並通過這種方式影響其後代對應激的應答情況。他們還發現這種變化是通過表觀遺傳學的方式或microRNA進行傳遞的，並非通過改變DNA。

　　在早期研究中，研究人員已經證實在交配之前通過更換籠盒或進行狐狸尿（捕獵者氣味）暴露處理雄性小鼠，使其處於應激狀態，其後代對應激的應答情況會存在障礙。研究人員將受到應激的雄性小鼠和未受到應激的雄性小鼠的精子進行對比分析，發現在應激小鼠精子中有9種microRNA表達出現升高。

　　為進一步證實這一結果，研究人員將這9種microRNA通過顯微注射的方式注入小鼠受精卵，隨後植入正常雌性小鼠體內進行繁殖，並以假注射或注射單個microRNA作為對照。當子代小鼠成年後，研究人員檢測了這些小鼠對應激的應答情況。研究人員表示，檢測結果與他們之前觀察到的結果完全匹配。

　　當接受多microRNA注射的小鼠受到輕微應激，它們體內可的鬆水平更低，同時在室旁核中存在幾百個基因出現顯著的表達變化，這表明這些小鼠在早期神經發育過程中存在非常廣泛的變化。

　　研究人員對這幾個microRNA的靶向mRNA進行了分析，結果表明來自母親卵細胞的mRNA受到了microRNA的攻擊，並導致這些受到攻擊的mRNA水平發生下降，研究人員還特別指出，這些受到影響的mRNA主要編碼參與染色質重塑的蛋白分子。

　　研究人員表示，他們接下來準備對導致microRNA釋放的上遊因子進行進一步研究以及是否能夠通過給予獎勵等方式對上述過程進行幹預，防止雄性親代將異常應激反應傳遞給下一代。

　　doi: 10.1073/pnas.1508347112

　　Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

　　Ali B. Rodgers, Christopher P. Morgan, N. Adrian Leu, and Tracy L. Bale

　　Epigenetic signatures in germ cells, capable of both responding to the parental environment and shaping offspring neurodevelopment, are uniquely positioned to mediate transgenerational outcomes. However, molecular mechanisms by which these marks may communicate experience-dependent information across generations are currently unknown. In our model of chronic paternal stress, we previously identified nine microRNAs (miRs) that were increased in the sperm of stressed sires and associated with reduced hypothalamic-pituitary-adrenal (HPA) stress axis reactivity in offspring. In the current study, we rigorously examine the hypothesis that these sperm miRs function postfertilization to alter offspring stress responsivity and, using zygote microinjection of the nine specific miRs, demonstrated a remarkable recapitulation of the offspring stress dysregulation phenotype. Further, we associated long-term reprogramming of the hypothalamic transcriptome with HPA axis dysfunction, noting a marked decreased in the expression of extracellular matrix and collagen gene sets that may reflect an underlying change in blood-brain barrier permeability. We conclude by investigating the developmental impact of sperm miRs in early zygotes with single-cell amplification technology, identifying the targeted degradation of stored maternal mRNA transcripts including sirtuin 1 and ubiquitin protein ligase E3a, two genes with established function in chromatin remodeling, and this potent regulatory function of miRs postfertilization likely initiates a cascade of molecular events that eventually alters stress reactivity. Overall, these findings demonstrate a clear mechanistic role for sperm miRs in the transgenerational transmission of paternal lifetime experiences.