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Developmental Vitamin D Deficiency in Pregnant Rats Does Not Induce Preeclampsia.

ABSTRACT: Preeclampsia is a pregnancy disorder characterized by hypertension. Epidemiological studies have associated preeclampsia with an increased risk of neurodevelopmental disorders in offspring, such as autism and schizophrenia. Preeclampsia has also been linked with maternal vitamin D deficiency, another candidate risk factor also associated with autism. Our laboratory has established a gestational vitamin-D-deficient rat model that shows consistent and robust behavioural phenotypes associated with autism- and schizophrenia-related animal models. Therefore, we explored here whether this model also produces preeclampsia as a possible mediator of behavioural phenotypes in offspring. We showed that gestational vitamin D deficiency was not associated with maternal blood pressure or proteinuria during late gestation. Maternal and placental angiogenic and vasculogenic factors were also not affected by a vitamin-D-deficient diet. We further showed that exposure to low vitamin D levels did not expose the placenta to oxidative stress. Overall, gestational vitamin D deficiency in our rat model was not associated with preeclampsia-related features, suggesting that well-described behavioural phenotypes in offspring born to vitamin-D-deficient rat dams are unlikely to be mediated via a preeclampsia-related mechanism.

SUBMITTER: Ali A

PROVIDER: S-EPMC8707812 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Developmental Vitamin D Deficiency in Pregnant Rats Does Not Induce Preeclampsia.

Ali Asad A Alexander Suzanne S Ko Pauline P Cuffe James S M JSM Whitehouse Andrew J O AJO McGrath John J JJ Eyles Darryl D

Nutrients 20211126 12

Preeclampsia is a pregnancy disorder characterized by hypertension. Epidemiological studies have associated preeclampsia with an increased risk of neurodevelopmental disorders in offspring, such as autism and schizophrenia. Preeclampsia has also been linked with maternal vitamin D deficiency, another candidate risk factor also associated with autism. Our laboratory has established a gestational vitamin-D-deficient rat model that shows consistent and robust behavioural phenotypes associated with ...[more]

PMID: 34959804

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Project description:BackgroundAutism spectrum disorder (ASD) is a group of neurodevelopmental disorders which are more common in males. The 'prenatal sex steroid' hypothesis links excessive sex-steroid exposure during foetal life with the behavioural differences observed in ASD. However, the reason why sex steroid exposure may be excessive remains unclear. Epidemiological studies have identified several environmental risk factors associated with ASD, including developmental vitamin D (DVD) deficiency. We have demonstrated in an animal model that DVD-deficiency is associated with a hyper-inflammatory response in placentas from male but not female foetuses. Vitamin D also regulates the expression of several steroidogenic enzymes in vitro. Therefore using this animal model, we have examined whether DVD-deficiency leads to increased sex-steroid levels in both the maternal and foetal compartments.MethodsFemale rats are fed a vitamin D deficient diet from 6 weeks before mating until tissue collection at embryonic day 18. We examined the levels of testosterone, androstenedione and corticosterone in maternal plasma, foetal brains and amniotic fluid. We further examined gene expressions of steroidogenic enzymes and DNA methylation of aromatase promoters in foetal brains as a potential molecular mechanism regulating testosterone expression.ResultsWe show that DVD-deficiency increases testosterone levels in maternal blood. We also show elevated levels of testosterone and androstenedione in the amniotic fluid of female but not male DVD-deficient foetuses. Testosterone levels were also elevated in DVD-deficient male brains. Vitamin D, like other steroid-related hormones, regulates gene expression via methylation. Therefore we examined whether the significant elevation in testosterone in male brains was due to such a potential gene-silencing mechanism. We show that the promoter of aromatase was hyper-methylated compared to male controls.LimitationsA reduction in aromatase, in addition to causing excessive testosterone, could also lead to a reduction in estradiol which was not examined here.ConclusionsThis study is the first to show how an epidemiologically established environmental risk factor for ASD may selectively elevate testosterone in male embryonic brains. These findings provide further mechanistic support for the prenatal sex steroid theory of ASD.

Project description:Hematopoiesis, a process that results in the differentiation of all blood lineages, is essential throughout life. The production of 1x1012 blood cells per day, including 200x109 erythrocytes, is highly dependent on nutrient consumption. Notably though, the relative requirements for micronutrients during the perinatal period, a critical developmental window for immune cell and erythrocyte differentiation, have not been extensively studied. More specifically, the impact of the vitamin C/ascorbate micronutrient on perinatal as compared to adult hematopoiesis has been difficult to assess in animal models. Even though humans cannot synthesize ascorbate, due to a pseudogenization of the L-gulono-γ-lactone oxidase (GULO) gene, its generation from glucose is an ancestral mammalian trait. Taking advantage of a Gulo-/- mouse model, we show that ascorbic acid deficiency profoundly impacts perinatal hematopoiesis, resulting in a hypocellular bone marrow (BM) with a significant reduction in hematopoietic stem cells, multipotent progenitors, and hematopoietic progenitors. Furthermore, myeloid progenitors exhibited differential sensitivity to vitamin C levels; common myeloid progenitors and megakaryocyte-erythrocyte progenitors were markedly reduced in Gulo-/- pups following vitamin C depletion in the dams, whereas granulocyte-myeloid progenitors were spared, and their frequency was even augmented. Notably, hematopoietic cell subsets were rescued by vitamin C repletion. Consistent with these data, peripheral myeloid cells were maintained in ascorbate-deficient Gulo-/- pups while other lineage-committed hematopoietic cells were decreased. A reduction in B cell numbers was associated with a significantly reduced humoral immune response in ascorbate-depleted Gulo-/- pups but not adult mice. Erythropoiesis was particularly sensitive to vitamin C deprivation during both the perinatal and adult periods, with ascorbate-deficient Gulo-/- pups as well as adult mice exhibiting compensatory splenic differentiation. Furthermore, in the pathological context of hemolytic anemia, vitamin C-deficient adult Gulo-/- mice were not able to sufficiently increase their erythropoietic activity, resulting in a sustained anemia. Thus, vitamin C plays a pivotal role in the maintenance and differentiation of hematopoietic progenitors during the neonatal period and is required throughout life to sustain erythroid differentiation under stress conditions.

Project description:Vitamin A plays an important role in the periods of rapid cellular growth and differentiation, especially during pregnancy, which is supplied by the mother to the fetus. The aim of this study is to assess the prevalence and potential influence factors of prenatal VAD of Chinese pregnant women.China National Nutrition and Health Survey 2010-2013(CHNNS2010-2013) is a nationally representative cross-sectional study. It involved the random selection of 150 districts (urban) or counties (rural). Each site randomly selected 30 pregnant women. Because volume of blood and incomplete data was taken into consideration,the final sample was formed by 1209 participants. Serum retinol concentrations were measured by high performance liquid chromatography. Characteristics of the pregnant women were collected by a questionnaire. Comparing retinol level across categories of independent variables was tested by the Mann-Whitney U test. Logistic and linear regression analyses were used to identify influence factors of Chinese pregnant women.The mean serum retinol level of the pregnant women was 1.63 μmol/L (95 % CI 1.60-1.67) and 64[5.3 % (95 % CI 4.03-6.56)] had VAD. The odds of VAD were significantly higher among the pregnant women in the poor rural areas and without college or university education and low- income. Pregnant women in the second and third trimester had 2.40 (95 % CI 1.05-5.46) and 2.82 (95 % CI 1.34-5.93) times increased odds of VAD compared with those in the first trimester respectively. Pregnant women of drinker had 3.10(1.65-5.81) times increased odds of VAD compared with those no drinker. Pregnant smokers had 5.68 (95 % CI 2.23-14.49) times higher odds of VAD compared with pregnant with non-smoker without passive smoking.VAD is of mild public-health issue in Chinese pregnant women. Such as : in the poor rural areas and without received college or university education and low- income and advanced gestational age and unhealthy lifestyles of pregnant women such as smoking and drinking. These were pertinent influence factors of VAD.

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Developmental Vitamin D Deficiency in Pregnant Rats Does Not Induce Preeclampsia.

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Developmental Vitamin D Deficiency in Pregnant Rats Does Not Induce Preeclampsia.

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