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Maternal protein restriction differentially alters the expression of AQP1, AQP9 and VEGFr-2 in the epididymis of rat offspring.

ABSTRACT: BACKGROUND:Maternal protein restriction causes sperm alterations in the offspring, most of which are associated with epididymal functions. Because fluid reabsorption/secretion dynamics in the epididymal environment play important roles in the process of sperm maturation and concentration, we investigated the effects of maternal protein restriction on the expression of aquaporins (AQP1 and AQP9), vascular endothelial growth factor (VEGFa), and its receptor VEGFr-2 in different stages of postnatal epididymal development. METHODS:Pregnant rats were divided into groups that received normoprotein (17% protein) and low-protein diets (6% protein) during gestation and lactation. After weaning, male rats only received the standard diet and were euthanized at the predetermined ages of 21, 44 and 120 days. RESULTS:Maternal protein restriction decreased AQP1 and AQP9 expression in the initial segment and caput epididymis compared to the increased expression of these proteins observed in the corpus and cauda at all ages. Although protein restriction reduced the microvasculature density (MVD) on postnatal day (PND) 21 and 44, the MVD was unaltered on PND 120. CONCLUSIONS:Maternal protein restriction changed the structure or function of the offspring's epididymis, specifically by affecting fluid dynamics and vasculogenesis in important stages of epididymis development.

SUBMITTER: Cavariani MM

PROVIDER: S-EPMC6387270 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Maternal protein restriction differentially alters the expression of AQP1, AQP9 and VEGFr-2 in the epididymis of rat offspring.

Cavariani Marilia Martins MM de Mello Santos Talita T Pereira Dhrielly Natalia DN de Almeida Chuffa Luiz Gustavo LG Felipe Pinheiro Patricia Fernanda PF Scarano Wellerson Rodrigo WR Domeniconi Raquel Fantin RF

International journal of molecular sciences 20190122 3

<h4>Background</h4>Maternal protein restriction causes sperm alterations in the offspring, most of which are associated with epididymal functions. Because fluid reabsorption/secretion dynamics in the epididymal environment play important roles in the process of sperm maturation and concentration, we investigated the effects of maternal protein restriction on the expression of aquaporins (AQP1 and AQP9), vascular endothelial growth factor (VEGFa), and its receptor VEGFr-2 in different stages of p ...[more]

PMID: 30678254

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Project description:BackgroundMaternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms.ObjectivesThe aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring.MethodsWistar rat dams were fed a control [normal-protein (NP); 17% protein] or an LP (8% protein) diet during pregnancy and lactation, and their male offspring were studied at 30 d of age. Direct measurements of baseline arterial blood pressure (ABP), heart rate (HR), and respiratory frequency (Rf) as well as peripheral chemoreflex activation (potassium cyanide: 0.04%) were recorded in pups while they were awake. In addition, recordings of the phrenic nerve (PN) and thoracic sympathetic nerve (tSN) activities were obtained from the in situ preparations. Hypoxia-inducible factor 1α (HIF-1α) expression was also evaluated in carotid bifurcation through a Western blotting assay.ResultsAt 30 d of age, unanesthetized LP rats exhibited enhanced resting Rf (P = 0.001) and similar ABP and HR compared with the NP rats. Despite their similar baseline ABP values, LP rats exhibited augmented low-frequency variability (∼91%; P = 0.01). In addition, the unanesthetized LP rats showed enhanced pressor (P = 0.01) and tachypnoeic (P = 0.03) responses to peripheral chemoreflex activation. The LP rats displayed elevated baseline tSN activity (∼86%; P = 0.02) and PN burst frequency (45%; P = 0.01) and amplitude (53%; P = 0.001) as well as augmented sympathetic (P = 0.01) and phrenic (P = 0.04) excitatory responses to peripheral chemoreflex activation compared with the NP group. Furthermore, LP rats showed an increase of ∼100% in HIF-1α protein density in carotid bifurcation compared with NP rats.ConclusionSympathetic-respiratory overactivity and amplified peripheral chemoreceptor responses, potentially through HIF-1α-dependent mechanisms, precede the onset of hypertension in juvenile rats exposed to protein undernutrition during gestation and lactation.

Project description:The risk of obesity (OB) in adulthood is strongly influenced by maternal body composition. Here we examined the hypothesis that maternal OB influences white adipose tissue (WAT) transcriptome and increases propensity for adipogenesis in the offspring, prior to the development of OB, using an established model of long-term metabolic programming. Employing an overfeeding-based rat model, in which exposure to OB is limited to preconception and gestation alone, we conducted global transcriptomic profiling in WAT, and gene/protein expression analysis of lipogenic and adipogenic pathways and examined adipogenic differentiation of WAT stromal-vascular cells ex vivo. Using reduced representation bisulfite sequencing we also evaluated genome-scale changes in DNA methylation in offspring WAT. Maternal OB led to extensive changes in expression of genes (± 1.8-fold, P ? .05), revealing a distinct up-regulation of lipogenic pathways in WAT. mRNA expression of a battery of sterol regulatory element-binding protein-1-regulated genes was increased in OB-dam offspring, which were confirmed by immunoblotting. In conjunction with lipogenic gene expression, OB-dam offspring showed increased glucose transporter-4 mRNA/protein expression and greater AKT phosphorylation following acute insulin challenge, suggesting sensitization of insulin signaling in WAT. Offspring of OB dams also exhibited increased in vivo expression of adipogenic regulators (peroxisome proliferator-activated receptor-?, CCAAT enhancer binding protein ? [C/EBP-?] and C/EBP-?), associated with greater ex vivo differentiation of WAT stromal-vascular cells. These transcriptomic changes were associated with alterations in DNA methylation of CpG sites and CGI shores, proximal to developmentally important genes, including key pro-adipogenic factors (Zfp423 and C/EBP-?). Our findings strongly suggest that the maternal OB in utero alters adipocyte commitment and differentiation via epigenetic mechanisms.

Dataset Information

Maternal protein restriction differentially alters the expression of AQP1, AQP9 and VEGFr-2 in the epididymis of rat offspring.

Publications

Maternal protein restriction differentially alters the expression of AQP1, AQP9 and VEGFr-2 in the epididymis of rat offspring.

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