Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts.
Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts.
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DOI：
10.1186/s12864-016-3366-y
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发表时间：
2016-12-08
期刊：
影响因子：
4.4
通讯作者：
Leroy JL
中科院分区：
文献类型：
--
作者：
Desmet KL;Van Hoeck V;Gagné D;Fournier E;Thakur A;O'Doherty AM;Walsh CP;Sirard MA;Bols PE;Leroy JL
与高产奶牛负能量平衡和女性肥胖相关的代谢应激是生育力下降的危险因素。非酯化脂肪酸（NEFA）参与了这种发病机制，因为它们危害卵母细胞和胚胎发育。越来越多的证据表明，母体代谢紊乱可能会扰乱后代的表观遗传编程，例如 DNA 甲基化。卵母细胞成熟和早期胚胎发育与甲基化变化同时发生，并且都对不利环境敏感。因此，我们研究了升高的 NEFA 浓度是否会影响卵母细胞和胚胎中 DNA 甲基化的建立和维持，从而改变转录组谱和所得囊胚的发育能力。在单独的实验中，牛卵母细胞和胚胎暴露于不同浓度的 NEFA。在第一个实验中，卵母细胞在含有以下成分的培养基中体外成熟 24 小时：1）生理（“BASAL”）浓度的油酸（OA）、棕榈酸（PA）和硬脂（SA）酸或 2）病理生理（“HIGH COMBI”）浓度的 OA、PA 和 SA。在第二个实验中，受精卵在 BASAL 或 HIGH COMBI 条件下体外培养 6.5 天。通过评估卵裂和囊胚率来评估发育能力。使用微阵列分析所得囊胚的整体基因表达和 DNA 甲基化。通过焦磷酸测序重新评估 DNA 甲基化数据。与 BASAL 暴露的卵母细胞和胚胎相比，HIGH COMBI 暴露的卵母细胞和胚胎发育成囊胚的能力较低（分别为 19.3% 与 23.2% 和 18.2% 与 25.3% 相比）（P < 0.05）。与暴露于 BASAL 的卵母细胞和胚胎相比，暴露于 HIGH COMBI 的卵母细胞和胚胎产生的囊胚的 DNA 甲基化和转录组指纹发生了改变。与成熟相比，培养期间暴露后基因表达和甲基化的差异更加明显，表明受精卵更容易受到不利环境的影响。受影响的主要基因网络与脂质和碳水化合物代谢、细胞死亡、免疫反应和代谢紊乱有关。总体而言，尽管获得了受影响途径的清晰概述，但囊胚之间甲基化的高度变异使得很难得出有关单个基因甲基化的结论。这可能为了解在患有脂肪分解疾病的母亲的后代中观察到的晚年胚胎丢失和代谢疾病的高发生率提供线索。
Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts. Bovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological (“BASAL”) concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological (“HIGH COMBI”) concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. Overall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.
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影响因子：
4.8
作者：
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影响因子：
3.6
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影响因子：
3.6
作者：
Aardema, Hilde;Lolicato, Francesca;Gadella, Bart M.
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Gadella, Bart M.