Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice
Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice
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DOI：
10.1113/jp278270
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发表时间：
2019-10-15
影响因子：
5.5
通讯作者：
Watkins, Adam J.
中科院分区：
文献类型：
--
作者：
Morgan, Hannah L.;Paganopoulou, Panaigota;Watkins, Adam J.
虽然母亲的饮食对成年后代健康的影响是很好的特点，父亲的饮食对他的后代的健康的作用仍然定义不清。我们建立了超最佳父亲低蛋白饮食对后代血管稳态的意义，并定义了精子和精浆对心血管健康的特定编程影响。雄性C57 BL 6小鼠喂食对照正常蛋白质饮食（NPD; 18%蛋白质）或等热量低蛋白质饮食（LPD; 9%蛋白质）至少7周。使用人工授精，结合输精管切除的男性交配，我们产生的后代来自NPD或LPD精子（无精浆），但在NPD或LPD精浆（无精子）的存在下。我们观察到，无论是LPD精子或精液在概念损害成年后代血管功能的反应，血管收缩剂和扩张剂。血管功能的这些变化的基础是血清，肺和肾脏血管紧张素转换酶（ACE）活性的显着变化，建立在F1后代从3周龄，保持到成年期，目前也在少年F2后代。此外，我们观察到多种中央肾素-血管紧张素系统调节剂在成年后代肾脏的差异表达。最后，父亲的饮食修改了成年F1雄性睾丸中DNA甲基化、组蛋白修饰和RNA甲基化的中央表观遗传调节因子的表达谱。这些新数据揭示了次优父亲营养对后代心血管健康的影响，通过精子和精浆特异性机制在连续几代中对后代心血管功能进行编程。
Although the impact of maternal diet on adult offspring health is well characterized, the role that a father's diet has on his offspring's health remains poorly defined. We establish the significance of a sup-optimal paternal low protein diet for offspring vascular homeostasis and define the sperm and seminal plasma specific programming effects on cardiovascular health. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 7 weeks. Using artificial insemination, in combination with vasectomized male mating, we generated offspring derived from either NPD or LPD sperm (devoid of seminal plasma) but in the presence of NPD or LPD seminal plasma (devoid of sperm). We observed that either LPD sperm or seminal fluid at conception impaired adult offspring vascular function in response to both vasoconstrictors and dilators. Underlying these changes in vascular function were significant changes in serum, lung and kidney angiotensin-converting enzyme (ACE) activity, established in F1 offspring from 3 weeks of age, maintained into adulthood and present also within juvenile F2 offspring. Furthermore, we observed differential expression of multiple central renin-angiotensin system regulators in adult offspring kidneys. Finally, paternal diet modified the expression profiles of central epigenetic regulators of DNA methylation, histone modifications and RNA methylation in adult F1 male testes. These novel data reveal the impact of sub-optimal paternal nutrition on offspring cardiovascular well-being, programming offspring cardiovascular function through both sperm and seminal plasma specific mechanisms over successive generations.