cholecalciferol and Fetal-Growth-Retardation

Maternal and perinatal undernutrition affects the lung development of litters and it may produce long-lasting alterations in respiratory health. This can be demonstrated using animal models and epidemiological studies. During pregnancy, maternal diet controls lung development by direct and indirect mechanisms. For sure, food intake and caloric restriction directly influence the whole body maturation and the lung. In addition, the maternal food intake during pregnancy controls mother, placenta, and fetal endocrine systems that regulate nutrient uptake and distribution to the fetus and pulmonary tissue development. There are several hormones involved in metabolic regulations, which may play an essential role in lung development during pregnancy. This review focuses on the effect of metabolic hormones in lung development and in how undernutrition alters the hormonal environment during pregnancy to disrupt normal lung maturation. We explore the role of GLP-1, ghrelin, and leptin, and also retinoids and cholecalciferol as hormones synthetized from diet precursors. Finally, we also address how metabolic hormones altered during pregnancy may affect lung pathophysiology in the adulthood.

Topics: Animals; Cholecalciferol; Female; Fetal Development; Fetal Growth Retardation; Ghrelin; Glucagon-Like Peptide 1; Hormones; Humans; Leptin; Lung; Malnutrition; Maternal Nutritional Physiological Phenomena; Pregnancy; Retinoids; Tretinoin

Vitamin D deficiency has been associated with adverse pregnant outcomes. Several studies investigated the effects of maternal vitamin D3 supplementation on fetal development with inconsistent results. The aim of this study was to investigate the effects of maternal supplementation with different doses of vitamin D3 on fetal development. Pregnant mice were administered with different doses of cholecalciferol (0, 2,000, 10,000, 40,000 IU/kg/day) by gavage throughout pregnancy. Fetal weight and crown-rump length were measured. Placental proliferation and mesenchymal characteristics were detected. HTR-8/SVneo cells were incubated in the absence or presence of calcitriol (500 nmol/L) to evaluate the effects of active vitamin D3 on migration and invasion of human trophoblast cells. Although a low dose of cholecalciferol was safe, fetal weight and crown-rump length were decreased in dams treated with high-dose cholecalciferol throughout pregnancy. Placental weight and labyrinth thickness were reduced in mice administered with high-dose cholecalciferol. An obvious calcification was observed in placentae of mice administered with high-dose cholecalciferol. Ki67-positive cells, a marker of placental proliferation, were reduced in mice administered with high-dose cholecalciferol. N-cadherin and vimentin, two mesenchymal markers, were decreased in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. MMP-2 and MMP-9, two matrix metalloproteinases, were downregulated in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. In addition, trophoblast migration and invasion were suppressed by calcitriol. Supplementation with high-dose cholecalciferol induces fetal growth restriction partially through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition.

Topics: Animals; Cell Proliferation; Cholecalciferol; Epithelial-Mesenchymal Transition; Female; Fetal Growth Retardation; Humans; Mice; Placenta; Pregnancy; Trophoblasts; Vitamins

We investigated associations between serum 25-hydroxyvitamin D (25(OH)D) in pregnancy and birth weight and other neonatal anthropometric measures. The present study was a population-based, multiethnic cohort study of 719 pregnant women (59 % ethnic minorities) in Oslo, Norway, delivering a singleton neonate at term and with birth weight measurements. In a representative sample, anthropometric measurements were taken. Maternal 25(OH)D was measured at gestational weeks 15 and 28. Women with 25(OH)D <37 nmol/l were recommended vitamin D3 supplementation. Separate linear regression analyses were performed to model the associations between 25(OH)D and each of the outcomes: birth weight, crown-heel length, head circumference, abdominal circumference, sum of skinfolds, mid-upper arm circumference and ponderal index. In early pregnancy, 51 % of the women were vitamin D deficient (25(OH)D<50 nmol/l). In univariate analyses and in models adjusting for maternal age, parity, education, prepregnancy BMI, season, gestational age and neonate sex, maternal 25(OH)D was significantly associated with birth weight, head circumference, abdominal circumference and ponderal index (P<0·05 for all), when used as a continuous variable and categorised (consistently low, consistently high, increasing and decreasing level). However, after adjusting for ethnicity, 25(OH)D was no longer associated with any of the outcomes. Sex-specific associations for abdominal circumference and sum of skinfolds were found (P for interaction<0·05). In conclusion, in a multiethnic cohort of pregnant women with high prevalence of vitamin D deficiency, we found no independent relation between maternal vitamin D levels and any of the neonatal anthropometric measures, and the strong association between ethnicity and neonatal outcomes was not affected by maternal vitamin D status.

Topics: 25-Hydroxyvitamin D 2; Adult; Birth Weight; Body Composition; Calcifediol; Cholecalciferol; Cohort Studies; Dietary Supplements; Female; Fetal Development; Fetal Growth Retardation; Humans; Infant, Newborn; Longitudinal Studies; Male; Maternal Nutritional Physiological Phenomena; Norway; Nutritional Status; Pregnancy; Pregnancy Complications; Prevalence; Prospective Studies; Vitamin D Deficiency

It is increasingly recognized that vitamin D3 (VitD3) has an anti-inflammatory activity. The present study investigated the effects of maternal VitD3 supplementation during pregnancy on LPS-induced placental inflammation and fetal intrauterine growth restriction (IUGR). All pregnant mice except controls were intraperitoneally injected with LPS (100 μg/kg) daily from gestational day (GD)15-17. In VitD3 + LPS group, pregnant mice were orally administered with VitD3 (25 μg/kg) before LPS injection. As expected, maternal LPS exposure caused placental inflammation and fetal IUGR. Interestingly, pretreatment with VitD3 repressed placental inflammation and protected against LPS-induced fetal IUGR. Further analysis showed that pretreatment with VitD3, which activated placental vitamin D receptor (VDR) signaling, specifically suppressed LPS-induced activation of nuclear factor kappa B (NF-κB) and significantly blocked nuclear translocation of NF-κB p65 subunit in trophoblast gaint cells of the labyrinth layer. Conversely, LPS, which activated placental NF-κB signaling, suppressed placental VDR activation and its target gene expression. Moreover, VitD3 reinforced physical interaction between placental VDR and NF-κB p65 subunit. The further study demonstrates that VitD3 inhibits placental NF-κB signaling in VDR-dependent manner. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity. Overall, the present study provides evidence for roles of VDR as a key regulator of placental inflammation.

Topics: Animals; Cholecalciferol; Female; Fetal Growth Retardation; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Placenta; Placenta Diseases; Pregnancy; Receptors, Calcitriol; Signal Transduction; Transcription Factor RelA