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在哺乳期前 14 周的不同喂养水平对奶牛犊牛血液端粒长度和线粒体 DNA 拷贝数的影响。

Effects of different feeding levels during a 14-week preweaning phase in dairy heifer calves on telomere length and mitochondrial DNA copy number in blood.

机构信息

Institute of Animal Science, Physiology Unit, University of Bonn, Katzenburgweg 7, 53115 Bonn, Germany.

Educational and Research Centre for Animal Husbandry, Hofgut Neumühle, 67728 Münchweiler an der Alsenz, Germany.

出版信息

J Dairy Sci. 2022 Oct;105(10):8509-8522. doi: 10.3168/jds.2022-21891. Epub 2022 Aug 31.

Abstract

Telomeres cap the ends of eukaryotic chromosomes, and the telomere length (TL) is related to cellular age. The mitochondrial DNA copy number (mtDNAcn) reflects the abundance of mitochondria in a cell. In addition to generating energy, mitochondria are also the main producers of reactive oxygen species, which in turn can accelerate TL attrition and impair mitochondrial function. Nutrition in early life could influence mtDNAcn and TL in later life. In the present study, we investigated the effects of feeding different levels of milk replacer (MR) on TL shortening and energetic status by examining mtDNAcn of heifers during their first year of life. In this study, whole blood samples were obtained from German Holstein heifer calves 36 to 48 h after birth (wk 1) and at wk 12 and wk 16 of life (n = 37), as well as from 31 calves when reaching 1 yr of age. Calves were fed either a high level of MR (14% solids) at 10 L/d (1.4 kg of MR/d; n = 18) or a restrictive low level at 5.7 L/d (0.8 kg of MR/d; n = 19) until linear weaning in wk 13 to 14 of life. Additional whole blood samples were taken from their respective dams 36 to 48 h after calving. Relative TL (qT) and mtDNAcn in cells from whole blood were measured by multiplex quantitative PCR. The greatest qT values were observed in neonates (36-48 h after birth), with decreasing qT values thereafter. Delta qT values were calculated as ΔqT = qT (first year of life) - initial qT (36-48 h after birth). We found no effect of the feeding regimen on qT values, but qT decreased with age. The mtDNAcn was lowest in neonates, increased until wk 12 of life, and then remained at a constant level until after weaning (wk 16). After the first year of life, mtDNAcn was decreased and returned to levels comparable to those of the neonatal stage. No differences in mtDNAcn were detectable between feeding groups within each time point. When comparing the values of qT and mtDNAcn between the calves and their dams after calving (36-48 h after birth and after calving), greater values were observed in calves than in dams. Delta qT values were negative in all but 2 calves (on the restricted diet), indicating that the change in TL with age was not uniform among individual animals, whereas no difference in mean ΔqT values occurred between the feeding groups. Additional analyses of the correlation between qT, mtDNAcn, and various indicators of oxidative status from birth until wk 16 of life did not indicate major interactions between oxidative status, qT and mtDNAcn. The results of this study support an age-dependent decrease of TL in calves independent of the MR feeding level and show the dynamic changes of mtDNAcn in early life.

摘要

端粒位于真核染色体的末端,端粒长度 (TL) 与细胞年龄有关。线粒体 DNA 拷贝数 (mtDNAcn) 反映了细胞中线粒体的丰度。除了产生能量外,线粒体还是活性氧物质的主要产生者,而活性氧物质反过来又可以加速 TL 损耗并损害线粒体功能。生命早期的营养可以影响生命后期的 mtDNAcn 和 TL。在本研究中,我们通过检查生命第一年中奶牛的 mtDNAcn,研究了不同水平的代乳料(MR)喂养对 TL 缩短和能量状态的影响。在这项研究中,我们在出生后 36 至 48 小时(第 1 周)、第 12 周和第 16 周以及 31 头小牛达到 1 岁时,从德国荷斯坦奶牛小牛中获得全血样本。小牛要么每天喂食高水平的 MR(14%固形物)10 升(1.4 公斤 MR/d;n=18),要么每天喂食低水平的限制型 MR(5.7 升/d;0.8 公斤 MR/d;n=19),直到生命第 13 至 14 周线性断奶。还从各自的母畜中采集了额外的全血样本,在产后 36 至 48 小时。通过多重定量 PCR 测量全血细胞中的相对 TL(qT)和 mtDNAcn。在新生儿(出生后 36-48 小时)中观察到最大的 qT 值,此后 qT 值逐渐降低。Delta qT 值的计算方法为 ΔqT = qT(生命的第一年)-初始 qT(出生后 36-48 小时)。我们发现喂养方案对 qT 值没有影响,但 qT 值随年龄增长而下降。mtDNAcn 在新生儿中最低,直到第 12 周生命期增加,然后在断奶(第 16 周)后保持稳定水平。在生命的第一年之后,mtDNAcn 减少并恢复到与新生儿阶段相当的水平。在每个时间点,在喂食组之间均未检测到 mtDNAcn 的差异。当比较产后(出生后 36-48 小时和产后)小牛与其母畜之间的 qT 和 mtDNAcn 值时,小牛中的值大于母畜中的值。除了 2 头(在限制饮食组)以外,所有小牛的 Delta qT 值均为负值,这表明 TL 随年龄的变化在个体动物之间并不均匀,而两组之间的平均 Delta qT 值没有差异。在生命的第 16 周之前,对 qT、mtDNAcn 与出生至第 16 周的各种氧化状态指标之间的相关性进行的进一步分析表明,氧化状态、qT 和 mtDNAcn 之间没有主要相互作用。这项研究的结果支持了 TL 在小牛中随年龄增长而独立于 MR 喂养水平而降低的结论,并显示了 mtDNAcn 在生命早期的动态变化。

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