Striking variation in the sex ratio of pups born to mice according to whether maternal diet is high in fat or carbohydrate

Abstract

In female mammals, it remains controversial whether maternal diet and particularly the source and availability of energy can influence sex of offspring born. Outbred female mice were fed ad libitum from 30 days to approximately 45 wk of age on defined, complete diets that differed only in their relative content of fat and carbohydrate to determine whether calorie source influenced litter size and sex ratio of pups. Diet 1 (very high in saturated fat, VHF) provided 60% of calories as fat, mainly lard. Diet 2 (low in saturated fat, LF) was low in fat (10% of calories) but high in carbohydrate. Mice delivered four litters of pups, resulting in a total of 1,048 young born over 108 pregnancies. Gestation length and litter size did not differ between VHF and LF groups and did not change as mice aged. Sex ratio of pups (fraction male) born to mothers on VHF diet was unusually high (0.67) and to mothers on LF diet very low (0.39) over litters 2, 3, and 4. This skewing of sex ratio was related to diets fed and not to body mass of mothers. Age of mothers was an important variable, however. Mice that were first bred at 10 wk of age delivered similar numbers of sons and daughters, whereas virgin mice bred later than 20 wk of age produced litters that were skewed toward males or females according to diet. The data show that the source of calories provided in a nutritionally complete diet to mature female mice can influence sex of offspring born.

Figure 1

Changes in mean body weight of female mice on the VHF and LF diets. The information is from one of the two studies from which the data in Table 2 were obtained. Two groups of eight mice were initially introduced to the diets when they were 30 days of age and maintained on the VHF (upper line) and LF (lower line) diets for ≈40 wk, during which time the mice delivered four sets of pups: a, male introduced; b, mean day of delivery; *, first parity 1; **, second parity; ***, third parity; ****, fourth parity. Pups were weaned at 21 days. The graph illustrates the rapid increase in body mass accompanying pregnancy, as well as the fall in weight after delivery and after weaning of pups. The number of mice successfully bred decreased from n = 8 for litters 1–3 to n = 5 for litter 4 when the mice in both groups proved difficult to breed. The results from the duplicate study were essentially indistinguishable from the one described here.

Figure 2

Frequency distribution of sex ratio (fraction males) within litters at parity 2, 3, and 4 for the VHF and LF dietary groups in the experiment described in Table 2. Each of the bars on that graph represents the number of litters with a sex ratio within the range ±0.05 of the number on the x axis; i.e., a value of 0.1 means there were no VHF litters with sex ratio between 0.05 and 0.15, whereas for LF there were two. Similarly, there were eight litters with a ratio between 0.75 and 0.85 on the VHF diet and one on the LF diet. Two VHF litters were entirely male and one LF litter was entirely female.