Differential Effects Of High-fat Diets Before Pregnancy And/or During Pregnancy On Fetal Growth Development

Background Obesity in women of childbearing age has become one of the major public health problems.Maternal obesity during pregnancy elevated risk of infertility,early pregnancy loss,stillbirth and preterm delivery.Numerous studies demonstrated that maternal obesity before pregnancy causes large for gestational age(LGA);however,animal studies have shown that the intrauterine environment associated with obesity can reduce fetal weight.The relationship between maternal obesity and fetal birth weight remains unclear.High-fat diets are a common dietary pattern to induce obesity.Therefore,it is especially interesting whether HFD at different stages disturbs fetal growth development.Objective The aim of the study was to investigate the effects of high-fat diets before pregnancy and/or during pregnancy on fetal development.Methods CD-1 female mice were fed with standard diets(SD)or high-fat diets(HFD).After 12 weeks,females were housed overnight with CD-1 males for mating purposes.Then,Females were checked next morning,and the presence of a vaginal plug was regarded as gestational day(GD)0.Pregnant mice in the SD group and HFD group were randomly divided into two groups: One group of previous diets,another group of exchange diets.All pregnant mice were anesthetized using a mixture of isoflurane and oxygen and then sacrificed on GD16.Fetal weight and crown-rump length were measured.Maternal serum,amniotic fluid and placentas were collected.Results Body weight of HFD-fed mice was significantly increased after 12 weeks of HFD as compared with SD-fed mice.Fertility rate was significantly decreased in HFD-fed mice as compared with SD-fed mice.There was no significant difference on the numbers of resorptions,dead fetuses,live fetuses and implantation sites per litter among different groups.Fetal weight and crown-rump length were increased in SD + HFD-fed mice,whereas were decreased in HFD + SD-fed mice.CRP and TNF-? in maternal serum and amniotic fluid were measured.In all HFD-fed groups,the levels of CRP and TNF-? in maternal serum and amniotic fluid were elevated.Placenta weight was elevated in SD + HFD-fed but not in HFD + SD-fed mice.Further analysis showed that Blood sinusoid areas,the number of CD34-positive cells,a marker of vascular endothelial cells,and the number of Ki67-positive cells,a marker of cell proliferation,were elevated in placental labyrinth layer of SD + HFD-fed mice,but decreased in HFD + SD-fed mice.The expressions of placental nutrient transporter genes were measured using real-time RTPCR.Placental Fatp1,a fatty acid transporter gene,was up-regulated in SD + HFD-fed mice.By contrary,placental fatp1,and snat2,a sodium-coupled neutral amino acid transporter 2,were down-regulated in HFD + SD-fed mice.Moreover,the levels of placental FATP4 and SNAT2 were up-regulated in SD + HFD-fed mice.Conclusions HFD before pregnancy and HFD during pregnancy differentially disturbs fetal growth development.HFD-before pregnancy-induced fetal SGA might be partially attributed to inflammatory cytokines.By contrary,HFD-during pregnancy-induced fetal overweight may be partially attributed to the increase of placental fatty acid transport capacity.