Effects of Diets Enriched in Omega-3 and Omega-6 Polyunsaturated Fatty Acids on Offspring Sex-Ratio and Maternal Behavior in Mice1

Abstract

There have been many trials describing the effects of polyunsaturated fatty acids (PUFA) on fecundity, neonatal development, and maternal behavior in humans, but few controlled studies in rodents. We examined the effects of a maternal diet high in omega 3 (N-3) or omega 6 (N-6) PUFA on NIH Swiss mice. Female mice were ad libitum fed one of three complete and balanced diets (N-3, enriched in menhaden oil; N-6, enriched in corn oil; C, control diet, Purina 5015) from age 4 wk until the end of the study. Mice were bred at approximately 19 wk and 27 wk of age, providing a total of 838 pups from 129 litters in two experiments. After weaning their pups from parity 1, behavior of dams was assessed on elevated-plus and open-field mazes. Although the fraction of male pups from the N-3 and C groups was not different from 0.5, dams on the N-6 diet birthed more daughters than sons (213 vs. 133; P < 0.001). Although maternal stress has been reported to favor birth of daughters, the behavior of N-6 dams was not different from controls. By contrast, the N-3 dams displayed greater anxiety, spending less time in the open arms and more time in the closed arms of the elevated maze and traveling less distance and exhibiting less exploratory behavior in the open field (P < 0.05). N-3 dams tended to produce smaller litters than C dams, and N-3-suckled pups gained less weight (P < 0.05). In conclusion, the N-3 diet had negative effects on murine fecundity and maternal behavior, whereas the N-6 diet favored birth of daughters.

Can mammalian mothers influence the sex of their offspring peri-conceptually?

“…Then, further investigation on the effect of high-fat diets (which involved discriminating between diets high in the omega 3 and omega 6 components of polyunsaturated fatty acids) found that the sex ratios were reversed (Fountain et al 2008). The mice fed the high-fat diet enriched with omega 6 gave birth to a significantly higher number of female offspring.…”

“…Recognising that testosterone underpins a tendency to dominant behaviour (Bouissou 1978, Christiansen 1998, Grant & France 2001, researchers who favoured the maternal dominance hypothesis sought an association between female testosterone and offspring sex ratio (Grant & Irwin 2005, Grant et al 2008, Helle et al 2008, Shargal et al 2008, while those opting for the good condition hypothesis sought links in the area of diet (Rosenfeld et al 2003, Rosenfeld & Roberts 2004, Cameron et al 2008, Mathews et al 2008, and, more explicitly, unsaturated fats , polyunsaturated fatty acids (Fountain et al 2008, Green et al 2008 and glucose (Kimura et al 2005).…”

“…More recently, experimental interventions have demonstrated a significant effect of pre-conceptual maternal diet on the sex ratio , Fountain et al 2008, Green et al 2008. Female mice fed a very high saturated fat diet had significantly more male offspring than either control or restricted fat diet females.…”

Sex differences in developmental programming models

“…Detecting a sex ratio skew in laboratory models of developmental programming is not straightforward, as many models cull litters to a standardised number of males and females, or a set low number of single sex offspring in order to maximise the plane of nutrition (Khan et al 2003, Chen et al 2008, Tarry-Adkins et al 2010) but do not report pre-culling litter size or gender distributions. Interestingly, however, a few studies have shown that the sex ratio in rodent models can be altered by changing maternal diet (Rosenfeld et al 2003, Rosenfeld & Roberts 2004, and a similar effect has been noted with calorie restriction (Meikle & Drickamer 1986) and increased fats in the maternal diet (Fountain et al 2008). It has been demonstrated that a mouse model utilising a maternal high-fat diet, which may be taken as a proxy for a nutrient-rich plentiful environment, produced litters skewed towards excess males (male fraction 0.67) whereas a low-fat diet in the same animals skewed the ratio towards excess female offspring (male fraction 0.39) (Rosenfeld et al 2003).…”

Disruption of adult expression of sexually selected traits by developmental exposure to bisphenol A

“…Two weeks after the Barnes Maze testing, exploratory and anxiety-related behaviors were assessed by using the EPM (66). Additional information is provided in SI Materials and Methods.…”