Relationship between diet and sex of offspring

描述（由申请人提供）：在哺乳动物中，改变母亲所吃食物的质量或数量是否会影响所生后代的性别比例，目前存在相当大的争议。在最初的实验中，我们比较了来自NIH瑞士和CF 1的近亲繁殖小鼠的幼崽的性别比例，这些小鼠喂食两种营养完全的饮食，它们的脂肪含量不同。第一组总甘油三酯含量低，但碳水化合物含量高（LF，低脂肪饮食），而第二组以猪油的形式提供60%的卡路里（VHF，高脂肪饮食）。饮食对产仔数量和妊娠期长短都没有影响，但高脂肪饮食的母亲生的儿子比女儿多，而且雄性偏向的比例很高，而低脂肪饮食的母亲则相反。性别比例偏斜与饮食有关，与母亲体重无关。然而，年龄是一个重要的变量。只有成熟的老鼠提供的性别比例在第一次怀孕时受到饮食的严重扭曲。第一个目标是产生关于饮食的性质和时间与性别比之间关系的信息。目标将是；1)在小鼠受孕前和妊娠早期只饲喂一段时间的饲粮时，观察幼鼠的性别比例；2)以分析性别偏倚现象的遗传基础为长期目标，通过对具有不同遗传背景的几个近交系小鼠进行测试，证实观察结果的普遍性；3)测试增加饮食中n-3不饱和脂肪酸的量是否会影响后代的性别比例，就像人类所建议的那样；4)确定减少VHF日粮小鼠的热量摄入是否会导致幼鼠性别比向下调整。第二个目标将是确定繁殖女性性别比例的失衡何时发生，并了解可能导致这种失衡的机制。实验将显示y精子在VHF小鼠的生殖道中到达或使卵母细胞受精方面是否比x精子有优势，同样，x精子在LF小鼠中是否有优势。我们将测试是否在受精后而不是之前根据性别选择受孕，如果是这样，选择过程是在植入之前还是之后进行。最后，我们将研究实验饮食是否会导致血清激素、血液电解质和代谢物的变化，以及生殖道环境的改变，从而使一种性别的概念可能比另一种性别在子宫内具有竞争优势。我们的观察结果可能会对人类生育能力的控制产生重大影响，为一系列实验室和农场动物提供一种根据喂养方式调整后代性别的实用方法，并为哺乳动物性别分配过程的存在提供进一步的证据，这一过程取决于食物资源的可用性和质量。

DESCRIPTION (provided by applicant): There is considerable controversy whether in mammals altering the quality or quantity of food eaten by the mother can bias the sex ratio of offspring born. In initial experiments we compared the sex ratio of pups from NIH Swiss and CF 1 outbred mice fed two nutritionally complete diets that differed in their content of fat. The first was low in total triglyceride but high in carbohydrate (LF, low fat diet), while the second provided 60% of the calories as lard (VHF, very high fat). The diets had no effect on either litter size or gestation length, but mothers on high fat produced many more sons than daughters and a striking proportion of male-biased litters, while the reverse was true on the low fat diet. The sex ratio skewing correlated with diet and was independent of maternal weight. Age was an important variable, however. Only mature mice provided sex ratios that were highly skewed by diet at first pregnancy. The first goal will be to generate information on the relationship between the nature and timing of the diet and sex ratio. The aims will be to; 1) follow sex ratios of pups when mice are provided the diets only for a limited period during the period preceding conception and during early pregnancy; 2) confirm the generality of the observations by testing several inbred strains of mouse with different genetic backgrounds with the long term goal of analyzing the genetic basis of the sex biasing phenomenon; 3) test whether increasing the amount of n-3 unsaturated fatty acids in the diet influences sex ratio of offspring, as has been suggested for humans; 4) determine whether reducing the caloric intake of mice on the VHF diet causes a downwards readjustment of the sex ratio of pups. A second goal will be to determine when the skewing in sex ratios in bred females occurs and to understand what mechanisms might be responsible. The experiments will show whether Y-sperm have some advantage over X-sperm in either reaching or fertilizing oocytes in the reproductive tract of VHF mice, and, likewise, whether X-sperm have some advantage in LF mice. We shall test whether conceptuses are selected according to sex after fertilization rather than before, and, if so, whether the selection process occurs prior to or subsequent to implantation. Finally, we shall examine whether the experimental diets cause changes in serum hormones, blood electrolytes and metabolites, and alterations in the reproductive tract environment in such a manner that conceptuses of one sex might have an in utero competitive advantage over the other. Our observations could have major implications for control of human fertility, provide a practical way of adjusting the sex of progeny for a range of laboratory and farm animals according to how they are fed, and lend further credence for the controversial existence of a process of sex allocation in mammals that depends on the availability and quality of food resources.