The placenta acts a regulator of nutrient composition and supply from mother to fetus and is the source of hormonal signals that affect maternal and fetal metabolism. Thus, appropriate development of the placenta is crucial for normal fetal development. We investigated the effect of gestational protein restriction (GPR) on placental morphology and mitochondrial function on day 19 of gestation. Pregnant dams were divided into two groups: normal (NP 17 % casein) or low-protein diet (LP 6 % casein). The placentas were processed for biochemical, histomorphometric and ultrastructural analysis. The integrity of rat placental mitochondria (RPM) isolated by conventional differential centrifugation was measured by oxygen uptake (Clark-type electrode). LP animals presented an increase in adipose tissue and triacylglycerol and a decrease in serum insulin levels. No alterations were observed in body, liver, fetus, or placenta weight. There was also no change in serum glucose, total protein, or lipid content. Gestational protein restriction had tissue-specific respiratory effects, with the observation of a small change in liver respiration (~13 %) and considerable respiratory inhibition in placenta samples (~37 %). The higher oxygen uptake by RPM in the LP groups suggests uncoupling between respiration and oxidative phosphorylation. In addition, ultrastructural analysis of junctional zone giant cells from LP placenta showed a disorganized cytoplasm, with loss of integrity of most organelles and intense vacuolization. The present results led us to hypothesize that GPR alters placental structure and morphology, induces sensitivity to insulin, mitochondrial abnormalities and suggests premature aging of the placenta. Further studies are needed to test this hypothesis.

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We recently showed that gestational protein restriction (GPR) alters the structure of the rat placenta on day 19 of gestation (dG). The aim of the study was to investigate the spatial and temporal immunolocalization of proliferating cell antigen Ki67 in normal and GPR placental development. Pregnant Wistar rats were divided into two groups: normal (NP, 17 % casein) or low-protein diet (LP, 6 % casein). Placentas and fetus were collected and weighed at 15, 17, 19 and 21 dG. Morphological, morphometric and ultrastructural analyses were performed. Immunoperoxidase was used to identify nuclear antigen Ki67 in placental sections. We observed a significant reduction in the number of trophoblast giant cells and glycogen cells in the LP group. Placental weight was significantly reduced only at 17 dG in the LP group, in parallel to a decrease in glycogen cells. From 15 to 21 dG, the thickness of the junctional zone (JZ) decreased in NP and LP animals, while that of the labyrinth zone (LZ) increased in parallel to a reduction in the number of proliferating cells in this LZ zone. GPR significantly inhibits cell proliferation in the JZ, especially at 15 and 17 dG. The ultrastructural appearance of the cytoplasm of giant and cytotrophoblastic cells indicates degeneration from 15 to 21 dG and this effect is enhanced in LP animals suggesting early aging. Offspring of NP dams were significantly heavier than offspring of LP dams at 21 dG. GPR causes modifications in specific regions of the placenta, cell proliferation inhibition and fetal growth restriction.

BackgroundThe dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood.ObjectivesThe aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60).MethodsPregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis.ResultsLP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression.ConclusionGPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium.

Poor nutrition during pregnancy causes permanent metabolic and/or structural adaptation in offspring. The adrenal gland produces various steroid hormones during pregnancy. Thus, this study aimed to evaluate the influence of diet during pregnancy on the adrenal glands of Wistar rats. For this, 10-week-old pregnant Wistar rats (p, n=15) and non-pregnant rats (np, n=15) were divided into three groups and received a normoproteic control diet (C, 17% casein, n=5), isocaloric low-protein diet (PR, 6% casein, n=5), or 50% calorie restriction (CR, 50% of the diet consumed by group C), over a period of 21 days. On the 21st day of gestation (21dG, p groups) or on the 21st day of diet (np groups), after anesthetic deepening, the right adrenal gland was collected, weighed (total mass), and prepared for inclusion in Paraplast for histomorphometric and immunohistochemical analysis (Ki-67, glucocorticoid receptors (GR), and mineralocorticoid receptor (MR)) in the different areas of the gland. Data, expressed as the mean and SD, were evaluated by one-way analysis of variance with Tukey's post-test (p < 0.05). CR in pregnancy increased the amount of GR, MR, and Ki-67 receptors in the adrenal gland. The npRC group showed highest GR staining compared to the animals that received a normal diet. Protein restriction in pregnancy decreases adrenal MR. The results allowed us to conclude that even without altering the weight of the adrenal glands, the pRC group suffered the most from stress during the study, suggesting that CR associated with pregnancy can cause morphofunctional changes in the adrenal glands.

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