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.
