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产前和产后轻度营养不足会影响周期性奶牛生殖道中的基因表达。

Pre- and post-partum mild underfeeding influences gene expression in the reproductive tract of cyclic dairy cows.

作者信息

Valour D, Hue I, Degrelle S A, Déjean S, Marot G, Dubois O, Germain G, Humblot P, Ponter A A, Charpigny G, Grimard B

机构信息

INRA, UMR1198 Biologie du Développement et Reproduction, F-78350, Jouy-en-Josas, France.

出版信息

Reprod Domest Anim. 2013 Jun;48(3):484-99. doi: 10.1111/rda.12113. Epub 2012 Nov 7.

Abstract

Undernutrition before and after calving has a detrimental effect on the fertility of dairy cows. The effect of nutritional stress was previously reported to influence gene expression in key tissues for metabolic health and reproduction such as the liver and the genital tract early after calving, but not at breeding, that is, between 70 and 90 days post-partum. This study investigated the effects of pre- and post-partum mild underfeeding on global gene expression in the oviduct, endometrium and corpus luteum of eight multiparous Holstein cows during the early and middle phases of an induced cycle 80 days post-partum. Four control cows received 100% of energy and protein requirements during the dry period and after calving, while four underfed received 80% of control diet. Oestrous synchronization treatment was used to induce ovulation on D80 post-partum. Oviducts, ovaries and the anterior part of each uterine horn were recovered surgically 4, 8, 12 and 15 days after ovulation. Corpora lutea were dissected from the ovaries, and the endometrium was separated from the stroma and myometrium in each uterine horn. The oviduct segments were comprised of ampulla and isthmus. RNAs from ipsi- and contralateral samples were pooled on an equal weight basis. In each tissue, gene expression was assessed on a custom bovine 10K array. No differentially expressed gene (DEG) in the corpus luteum was identified between underfed and control, conversely to 293 DEGs in the oviduct vs 1 in the endometrium under a false discovery rate (FDR) < 0.10 and 1370 DEGs vs 3, respectively, under FDR < 0.15. Additionally, we used dedicated statistics (regularized canonical correlation analysis) to correlate the post-partum patterns of six plasma metabolites and hormones related to energy metabolism measured weekly between calving and D80 with gene expression. High correlations were observed between post-partum patterns of IGF-1, insulin, β-hydroxybutyrate and the expression in the oviduct of genes related to reproductive system disease, connective tissue disorders and metabolic disease. Moreover, we found special interest in the literature to retinoic acid-related genes (e.g. FABP5/CRABP2) that might indicate abnormalities in post-partum tissue repair mechanisms. In conclusion, this experiment highlights relationships between underfeeding and gene expression in the oviduct and endometrium after ovulation in cyclic Holstein cows. This might help to explain the effect of mild undernutrition on fertilization failure and early embryonic mortality in post-partum dairy cows.

摘要

产犊前后的营养不足会对奶牛的繁殖力产生不利影响。营养应激的影响此前据报道会在产犊后早期影响代谢健康和繁殖的关键组织如肝脏和生殖道中的基因表达,但在配种时,即产后70至90天之间则不会。本研究调查了产后80天诱导周期的早期和中期,产前和产后轻度饲喂不足对8头经产荷斯坦奶牛输卵管、子宫内膜和黄体中全局基因表达的影响。4头对照奶牛在干奶期和产犊后接受100%的能量和蛋白质需求,而4头饲喂不足的奶牛接受对照日粮的80%。采用发情同步处理在产后第80天诱导排卵。在排卵后4、8、12和15天通过手术采集输卵管、卵巢和每个子宫角的前部。从卵巢中分离黄体,从每个子宫角的基质和肌层中分离子宫内膜。输卵管段由壶腹和峡部组成。同侧和对侧样本的RNA按等重量混合。在每个组织中,在定制的牛10K阵列上评估基因表达。在饲喂不足组和对照组之间未在黄体中鉴定出差异表达基因(DEG),相反,在错误发现率(FDR)<0.10时,输卵管中有293个DEG,而子宫内膜中只有1个,在FDR<0.15时,分别为1370个DEG和3个。此外,我们使用专门的统计方法(正则化典型相关分析)将产犊至产后第80天期间每周测量的与能量代谢相关的六种血浆代谢物和激素的产后模式与基因表达相关联。观察到胰岛素样生长因子-1、胰岛素、β-羟基丁酸的产后后模式与生殖系统疾病、结缔组织疾病和代谢疾病相关基因在输卵管中的表达之间存在高度相关性。此外,我们在文献中对可能表明产后组织修复机制异常的视黄酸相关基因(如FABP5/CRABP2)特别感兴趣。总之,本实验突出了周期性荷斯坦奶牛排卵后输卵管和子宫内膜中饲喂不足与基因表达之间的关系。这可能有助于解释轻度营养不足对产后奶牛受精失败和早期胚胎死亡的影响。

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