The fetal period represents an important window of susceptibility for later obesity and metabolic disease. Maternal vitamin D deficiency (VDD) during pregnancy is a global concern that may have long-lasting consequences on offspring metabolic health. We sought to determine whether a VDD in utero environment affects fetal adipose tissue development and offspring metabolic disease predisposition in adulthood. Furthermore, we sought to explore the extent to which the VDD intrauterine environment interacts with genetic background or postnatal environment to influence metabolic health. Eight-week-old P0 female C57BL/6J mice were fed either a VDD diet or sufficient diet (VDS) from four weeks before pregnancy (periconception) then bred to male A vy /a mice. Females were maintained on the diets throughout gestation. At weaning, A vy /a and a/a male F1 offspring were randomized to low-fat (LFD) or high-fat diet (HFD) until 19 weeks of age, at which point serum and adipose tissue were harvested for analyses. Mice born to VDD dams weighed less at weaning than offspring born to VDS dams but experienced rapid weight gain in the four weeks post weaning, and acquired a greater ratio of perigonadal (PGAT) to subcutaneous (SQAT) than control offspring. Additionally, these mice were more susceptible to HFD-induced adipocyte hypertrophy. Offspring of VDD dams also had greater expression of Pparg transcript. These novel findings demonstrate that in utero VDD, an easily correctable but highly prevalent health concern, predisposes offspring to long-term adipose tissue consequences and possible adverse metabolic health complications.
Anthony M Belenchia, Sarah A Johnson, Mark R Ellersieck, Cheryl S Rosenfeld and Catherine A Peterson
J J Whyte, A P Alexenko, A M Davis, M R Ellersieck, E D Fountain and C S Rosenfeld
We examined the effects of three maternal diets (very high fat (VHF), low fat (LF), and control (Purina 5015)) on serum steroids, free fatty acids (FFA), and vaginal pH in National Institutes of Health Swiss mice. Females were fed (VHF, n = 33; LF, n = 33; 5015, n = 48) from 4 to 16 weeks of age. Following breeding, female serum was collected at 0.5 (pre-implantation, early diestrus) or 8.5 (post-implantation, mid-diestrus) days post-coitus (dpc). The serum concentrations of 17β-estradiol, testosterone, progesterone, and FFA were analyzed at both collection points, and vaginal pH at 0.5 dpc. Striking differences in steroids and FFA were observed at 0.5 dpc among the groups. Estradiol was higher in the VHF (14.1 ± 3.0 pg/ml), compared with LF mice (5.2 ± 2.3 pg/ml; P≤ 0.05). In contrast, 0.5 dpc testosterone was lower in the VHF (10.5 ± 3.0 pg/ml) versus the LF group (32.7 ± 8.4 pg/ml; P≤ 0.05). At 8.5 dpc, progesterone was higher in the VHF (89.6 ± 6.7 ng/ml) versus the 5015 group (60.1 ± 4.9 ng/ml; P≤ 0.05). VHF mice had higher FFA concentrations at 0.5 dpc (1.0 ± 0.2 mmol/l) than LF and control mice (0.5 ± 0.1 and 0.6 ± 0.1 mmol/l respectively; P≤ 0.05). At 8.5 dpc, VHF females had higher serum FFA (0.8 ± 0.1 mmol/l) than LF and control females (0.4 ± 0.1 and 0.6 ± 0.1 mmol/l; P≤ 0.05). Mean vaginal pH of VHF females (6.41 ± 0.09) was lower than 5015 females (6.76 ± 0.10; P≤ 0.05). These diet-induced alterations in serum steroid and FFA concentrations might affect several reproductive processes, including preferential fertilization by one class of sperm over the other and sex bias in pre- and post-implantational embryonic development.