title: 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.
authors.affiliation: Dept. of Reproductive Medicine, University of California, San Diego, La Jolla, CA, 92093, United States. akauffman@ucsd.edu
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kauffman
authors.forename: Karolina
authors.initials: K
authors.lastname: Bojkowska
authors.forename: Emilie F
authors.initials: EF
authors.lastname: Rissman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D004198:Disease Susceptibility; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005260:Female; D005298:Fertility / Q000502:physiology*; D047109:Fetal Development / Q000502:physiology*; D008098:Litter Size; D008297:Male; D009752:Nutritional Status; D011247:Pregnancy / Q000502:physiology*; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal; D012726:Sexual Behavior, Animal; D012788:Shrews; D013997:Time Factors