Critical periods of susceptibility to short-term energy challenge during pregnancy: Impact on fertility and offspring development

Abstract

In female mammals, reproduction is tightly regulated by energy status and food availability. Although acute energetic challenges inhibit female reproductive behavior and gonadotropin secretion, less attention has been given to the effects of short-term energetic challenge on pregnancy and gestation. Furthermore, species differences in pregnancy physiology necessitate more detailed analyses of specific pregnancy models. Here, we studied musk shrews, which display induced ovulation and obligate delayed implantation, and whose reproductive physiology is tightly linked to metabolic status. We tested whether acute energetic challenges of varied degrees given at specific pregnancy stages (including before and after delayed implantation) have different effects on gestational outcome and offspring postnatal development. We found that 48 h of either 40% or 50% food restriction, which reduced body weight and strongly inhibited sexual behavior, had minimal effects on pregnancy success and litter dynamics when administered early in gestation (pre-implantation). However, <30% of females experiencing short-term food restriction later in gestation successfully gave birth (versus > or =70% of ad-libitum fed controls), and the pups of these food-restricted females exhibited a 30% slower postnatal growth trajectory. Interestingly, although pregnancy success and litter dynamics were unaffected by food restriction before implantation, gestation length was increased by metabolic challenges experienced at this time, indicating that energy status may regulate the timing of implantation. We conclude that 1) there are critical periods of pregnancy, particularly after implantation, when short-term, mild energetic challenges have significant impacts on fertility and offspring postnatal development, and 2) delayed implantation may have evolved, in part, as a buffering mechanism to prevent pregnancy failure during impaired energy balance in early gestation.

Figure 1

Schematic of the major physiological events and stages of gestation in female musk shrews (28). Double arrows above the horizontal bar depict 2 day periods when food restriction (40% or 50% decrease) was administered in the present experiments. P4, progesterone.

Figure 2

Mean ± S.E.M. body weights (A) and daily food intake (B) of female musk shrews over the course of pregnancy. Shrews were fed ad-libitum throughout the experiment or food-restricted (FR) for 48 h (40% or 50% decrease) just prior to mating with a stud male. Day of mating is considered beginning of pregnancy (E0).

Figure 3

(A) Mean ± S.E.M. body weights of female musk shrews over the course of pregnancy. Shrews were fed ad-libitum throughout gestation or moderately food-restricted for 48 h at various time points (40% decrease). Day of mating is considered beginning of pregnancy (E0). (B) Mean ± S.E.M. % increase in body weight (BW) from the beginning of pregnancy (E0) to last week of gestation (E28). * Significantly lower than ad-libitum fed controls.

Figure 4

(A) Percent of mated female shrews successfully delivering litters after moderate food restriction. Females were either maintained on an ad-libitum fed regimen for the entire duration of pregnancy or were food restricted 40% for 48 h at specific stages of gestation. (B–D) Parameters of gestation and litters of pregnant females exposed to 40% food restriction for 48 h during different stages of gestation. (B) Mean ± S.E.M. duration of gestation. (C) Mean ± S.E.M. litter size. (D). Mean ± S.E.M. individual pup body weight (BW) on postnatal day 5. For all panels: * Significantly different from ad-libitum fed controls.

Figure 5

(A) Mean ± S.E.M. body weights of female shrews that were fed ad-libitum throughout gestation or severely food-restricted for 48 h at various time points (fed 50% of daily food intake). Day of mating is considered beginning of pregnancy (E0). (B) Mean ± S.E.M. % increase in body weight (BW) from the beginning of pregnancy (E0) to last week of gestation (E28). * Significantly lower than ad-libitum fed controls.

Figure 6

(A) Percent of mated female shrews successfully delivering litters after severe food restriction. Females were either maintained on an ad-libitum fed regimen for the entire duration of pregnancy or were food restricted for 48 h (50% decrease) at specific stages of gestation. (B) Mean ± S.E.M. duration of gestation. For both panels: * Significantly different from ad-libitum fed controls.

Figure 7

Litter parameters and offspring development after pregnant females were exposed to 48 h of 50% food restriction at different stages of gestation. (A) Mean ± S.E.M. litter size. (B) Mean ± S.E.M. individual pup body weight (BW) on postnatal day 2. (C) Mean ± S.E.M. individual pup body weight (BW) on postnatal day 5. (D). Mean ± S.E.M. growth rate of pups (g/day) from postnatal day 2 to postnatal day 5. For all panels: * Significantly different from ad-libitum fed controls.