Improvement in glucose metabolism in adult male offspring of maternal mice fed diets supplemented with inulin via regulation of the hepatic long noncoding RNA profile.

Maternal overnutrition during pregnancy and lactation is an important risk factor for the later development of metabolic disease, especially diabetes, among mothers and their offspring. As a fructan-type plant polysaccharide, inulin has prebiotic functions and is widely used as a natural antidiabetic supplement. However, to date, the mechanism of maternal inulin treatment in the livers of offspring has not been addressed, especially with respect to long noncoding RNAs (lncRNAs). In this study, female C57BL6/J mice were fed either a high-fat diet (HFD) with or without inulin supplementation or a standard rodent diet (SD) during gestation and lactation. After the offspring were weaned, they were fed a SD for 5 weeks. At 8 weeks of age, the glucose metabolism indexes of the offspring were assessed, and their livers were collected to assay lncRNA and mRNA profiles to investigate the effects of early maternal inulin intervention on offspring. Our results indicate that male offspring from HFD-fed dams displayed glucose intolerance and an insulin resistance phenotype at 8 weeks of age. Early maternal inulin intervention improved glucose metabolism in male offspring of mothers fed a HFD during gestation and lactation. The lncRNA and mRNA profile data revealed that compared with the offspring from HFD dams, offspring from the early inulin intervention dams had 99 differentially expressed hepatic lncRNAs and 529 differentially expressed mRNAs. The differentially expressed lncRNA-mRNA coexpression analysis demonstrated that early maternal inulin intervention may change hepatic lncRNA expression in offspring; there lncRNAs are involved in metabolic pathways and the AMP-activated protein kinase signaling pathway. Importantly, the early maternal inulin intervention alleviated glucose metabolism by inhibiting the lncRNA Serpina4-ps1/let-7b-5p/Ppargc1a as a competing endogenous RNA in male offspring.

Maternal pregnancy vitamin D supplementation increases offspring bone formation in response to mechanical loading: Findings from a MAVIDOS Trial sub-study.

The Maternal Vitamin D Osteoporosis (MAVIDOS) trial reported higher total body bone mineral content in winter-born infants of mothers receiving vitamin D supplementation [1000 IU/day cholecalciferol] compared with placebo from 14 weeks gestation until delivery. This sub-study aimed to determine whether antenatal vitamin D supplementation altered postnatal bone formation in response to mechanical stimulation. Thirty-one children born to MAVIDOS participants randomised to either placebo (n=19) or cholecalciferol (n=12) were recruited at age 4-5 years. Children received whole body vibration (WBV) for 10 minutes on 5 consecutive days. Fasting blood samples for bone homeostasis, 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and bone turnover markers (Pro-collagen Type 1 N-terminal propeptide, P1NP; Cross-linked C-telopeptide of Type I Collagen, CTX) were collected pre-WBV and on day 8 (D8). Mean changes (D) in P1NP (ng/ml) between baseline and D8 in the vitamin-D intervention and placebo groups were 40.6 and -92.6 respectively and mean changes (Δ) in CTX (ng/ml) were 0.034 (intervention) and -0.084 (placebo) respectively. Between-group DP1NP difference was 133.2ng/ml [95% CI 0.4, 266.0; p=0.049] and ΔCTX 0.05ng/ml (95% CI -0.159, 0.26ng/mL; p=0.62). Antenatal vitamin-D supplementation resulted in increased P1NP in response to WBV, suggesting early life vitamin D supplementation increases the anabolic response of bone to mechanical loading in children.

Perinatal exposure to endocrine disrupting compounds and the control of feeding behavior-An overview.

Endocrine disrupting compounds (EDC) are ubiquitous environmental contaminants that can interact with steroid and nuclear receptors or alter hormone production. Many studies have reported that perinatal exposure to EDC including bisphenol A, PCB, dioxins, and DDT disrupt energy balance, body weight, adiposity, or glucose homeostasis in rodent offspring. However, little information exists on the effects of perinatal EDC exposure on the control of feeding behaviors and meal pattern (size, frequency, duration), which may contribute to their obesogenic properties. Feeding behaviors are controlled centrally through communication between the hindbrain and hypothalamus with inputs from the emotion and reward centers of the brain and modulated by peripheral hormones like ghrelin and leptin. Discrete hypothalamic nuclei (arcuate nucleus, paraventricular nucleus, lateral and dorsomedial hypothalamus, and ventromedial nucleus) project numerous reciprocal neural connections between each other and to other brain regions including the hindbrain (nucleus tractus solitarius and parabrachial nucleus). Most studies on the effects of perinatal EDC exposure examine simple crude food intake over the course of the experiment or for a short period in adult models. In addition, these studies do not examine EDC's impacts on the feeding neurocircuitry of the hypothalamus-hindbrain, the response to peripheral hormones (leptin, ghrelin, cholecystokinin, etc.) after refeeding, or other feeding behavior paradigms. The purpose of this review is to discuss those few studies that report crude food or energy intake after perinatal EDC exposure and to explore the need for deeper investigations in the hypothalamic-hindbrain neurocircuitry and discrete feeding behaviors.

Placental adaptations to micronutrient dysregulation in the programming of chronic disease.

Poor nutrition during pregnancy is known to impair foetal development and increase the risk of chronic disease in offspring. Both macronutrients and micronutrients are required for a healthy pregnancy although significantly less is understood about the role of micronutrients in the programming of chronic disease. This is despite the fact that modern calorie rich diets are often also deficient in key micronutrients. The importance of micronutrients in gestational disorders is clearly understood but how they impact long term disease in humans requires further investigation. In contrast, animal studies have demonstrated how diets high or low in specific micronutrients influence offspring physiology. Many of these studies highlight the importance of the placenta in determining disease risk. This review will explore the effects of individual vitamins, minerals and trace elements on offspring disease outcomes and discuss several key placental adaptations that are affected by multiple micronutrients. These placental adaptations include micronutrient induced dysregulation of oxidative stress, altered methyl donor availability and its impact on epigenetic mechanisms as well as endocrine dysfunction. Critical gaps in our current knowledge and the relative importance of different micronutrients at different gestational ages will also be highlighted. Finally, this review will discuss the need for further studies to characterise the micronutrient status of Australian women of reproductive age and correlate micronutrient status to placental adaptations, pregnancy complications and offspring disease.

A short-term transition from a high-fat diet to a normal-fat diet before pregnancy exacerbates female mouse offspring obesity.

BACKGROUND/OBJECTIVES: Recent findings have highlighted the detrimental influence of maternal overnutrition and obesity on fetal development and early life development. However, there are no evidence-based guidelines regarding the optimal strategy for dietary intervention before pregnancy. SUBJECTS/METHODS: We used a murine model to study whether switching from a high-fat (HF) diet to a normal-fat (NF) diet (H1N group) 1 week before pregnancy could lead to in utero reprogramming of female offspring obesity; comparator groups were offspring given a consistent maternal HF group or NF group until weaning. After weaning, all female offspring were given the HF diet for either 9 or 12 weeks before being killed humanely. RESULTS: H1N treatment did not result in maternal weight loss before pregnancy. NF offsprings were neither obese nor glucose intolerant during the entire experimental period. H1N offsprings were most obese after the 12-week postweaning HF diet and displayed glucose intolerance earlier than HF offsprings. Our mechanistic study showed reduced adipocyte insulin receptor substrate 1 (IRS1) and hepatic IRS2 expression and increased adipocyte p-Ser(636/639) and p-Ser(612) of H1N or HF offspring compared with that in the NF offspring. Among all groups, the H1N offspring had lowest level of IRS1 and the highest levels of p-Ser(636/639) and p-Ser(612) in gonadal adipocyte. In addition, the H1N offspring further reduced the expression of Glut4 and Glut2, vs those of the HF offspring, which was lower compared with the NF offspring. There were also enhanced expression of genes inhibiting glycogenesis and decreased hepatic glycogen in H1N vs HF or NF offspring. Furthermore, we showed extremely higher expression of lipogenesis and adipogenesis genes in gonadal adipocytes of H1N offspring compared with all other groups. CONCLUSIONS: Our results suggest that a transition from an HF diet to an NF diet shortly before pregnancy, without resulting in maternal weight loss, is not necessarily beneficial and may have deleterious effects on offspring.

Polyunsaturated fatty acids and fetal brain development.

QUESTION: I have learned that one of the manufacturers of prenatal vitamins has added omega-3 fatty acids and claims that they help support fetal cognitive health and brain function. Is this based on evidence? ANSWER: The claim that polyunsaturated fatty acids help improve fetal brain and eye development has been made for more than a decade. Unfortunately it is not supported by evidence-based science. Long-term studies have failed to show such effects. Implying to women that using these products will improve the brain development of their children is unwarranted and misleading. Health Canada should clarify the contradictions in its statements about omega-3 fatty acids.

Spermatogenesis recovery in protein-restricted rats subjected to a normal protein diet after weaning.

This study investigated the pre- and postnatal effects of protein restriction (8% vs 20% crude protein) on different parameters of spermatogenesis in adult rat offspring. Body and testis weights as well as the seminiferous tubular diameter were reduced in those animals that received the protein-restricted diet after weaning, although these parameters recovered when a 20% protein diet was offered subsequently. The numbers of spermatogonia, spermatocytes, spermatids and Leydig cells were reduced in undernourished animals, whilst the Sertoli cell number did not change. Prenatal programming effect was observed only in the spermatogonial or proliferative phase of spermatogenesis. However, the intake of the normal protein diet after weaning brought many of the testicular parameters evaluated back to normal in 70-day-old rats. A significant reduction of the meiotic index, Sertoli cell supporting capacity and spermatogenic efficiency was observed in animals subjected to protein undernutrition throughout their lives. The data presented show that protein restriction impairs the normal development of the testis in different ways, depending on the period during which the restriction was imposed, and the negative effects on spermatogenesis are more severe when undernutrition occurs from conception to adulthood; however, the return to a normal protein diet after weaning recovers the spermatogenic process.

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome.

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer's disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS.

Developmental changes in embryonic hypothalamic neurons during prenatal fat exposure.

Maternal consumption of a fat-rich diet during pregnancy, which causes later overeating and weight gain in offspring, has been shown to stimulate neurogenesis and increase hypothalamic expression of orexigenic neuropeptides in these postnatal offspring. The studies here, using an in vitro model that mimics in vivo characteristics after prenatal high-fat diet (HFD) exposure, investigate whether these same peptide changes occur in embryos and if they are specific to neurons. Isolated hypothalamic neurons were compared with whole hypothalamus from embryonic day 19 (E19) embryos that were prenatally exposed to HFD and were both found to show similar increases in mRNA expression of enkephalin (ENK) and neuropeptide Y (NPY) compared with that of chow-exposed embryos, with no change in melanin-concentrating hormone, orexin, or galanin. Further examination using immunofluorescence cytochemistry revealed an increase in the number of cells expressing ENK and NPY. By plotting the fluorescence intensity of each cell as a probability density function, three different populations of neurons with low, medium, or high levels of ENK or NPY were found in both HFD and chow groups. The prenatal HFD shifted the density of neurons from the population containing low peptide levels to the population containing high peptide levels. This study indicates that neuronal culture is a useful in vitro system for studying diet effects on neuronal development and shows that prenatal HFD exposure alters the population of hypothalamic neurons containing ENK and NPY in the embryo. These changes may contribute to the increase in HFD intake and body weight observed in offspring.

Maternal micronutrient supplementation suppresses T cell chemokine receptor expression and function in F1 mice.

Prenatal environmental exposures play a critical role in determining late-life chronic disease susceptibility. However, the mechanisms linking the in utero environment and disease development in the offspring are poorly understood. Recent investigations have confirmed a central pathogenic role of T cell chemokine receptors, particularly C-C chemokine receptor (CCR) 2 and CCR5, in chronic inflammatory conditions. This study was designed to determine the effect of a synthetic prenatal micronutrient supplementation (MS) diet rich in methionine pathway metabolites on the T cell chemokine system in F1 C57Bl/6 mice. Female mice were fed either an MS or control diet 3 wk prior to mating, during pregnancy, and lactation. At 4 wk of age, F1 mice were killed for experiments or were fed the standard NIH-31 diet and allowed to age. Food consumption, maternal weight gain, and litter size were similar in dams fed the control and MS diets. However, the F1 offspring of dams fed the MS diet were smaller in size (P < 0.001). T cells from the MS F1 offspring had global hypermethylation compared with control F1 offspring (P < 0.005), corresponding to lower T cell chemokine receptor expression [CCR2 (P < 0.001), CCR5 (P < 0.001), and C-x-C chemokine receptor 3 (P < 0.01)] and cytokine expression [TNFα (P < 0.05), IL-2 (P < 0.001), and IL-4 (P < 0.01)]. Reduced T cell chemokine receptor gene expression in MS F1 mice was associated with decreased chemotaxis in vitro to C-C chemokine ligand (CCL) 2 and C-X-C chemokine ligand 10 (P < 0.01) and in vivo to CCL2 (P < 0.01). Taken together, the results suggest that epigenetic alteration through prenatal diet manipulation reduces the response to proinflammatory signals in mice.

The impact of prenatal vitamin A and zinc supplementation on growth of children up to 2 years of age in rural Java, Indonesia.

OBJECTIVE: To determine whether prenatal vitamin A and/or Zn supplementation affects postnatal growth. DESIGN: Follow-up of a randomized controlled trial monitoring growth in children from birth up to 24 months of age. SETTING: Central Java, Indonesia. SUBJECTS: Children (n 343) of mothers participating in a double-blinded, randomized controlled study of vitamin A and/or Zn supplementation during pregnancy. We report the effects of prenatal supplementation on infant growth, measured as weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and weight-for-height Z-scores (WHZ ), from 0 to 24 months, as well as differences in growth faltering among the supplementation groups. RESULTS: For HAZ, the absolute differences between the vitamin A-only and vitamin A + Zn groups at 3 and 9 months were 0·34 SD and 0·37 SD, respectively, and the absolute difference between the vitamin A-only and Zn-only groups at 18 months was 0·31 SD. Compared with placebo, none of the supplements affected growth. Defining growth faltering as a downward crossing of two or more major percentile lines, 50-75% of the children were found to be growth faltering within 9 months of age, whereas 17% and 8% scored <-2 SD for WAZ and HAZ, respectively. Prenatal supplementation did not reduce the prevalence of growth faltering. CONCLUSIONS: Prenatal vitamin A supplementation had a small but significant effect on postnatal growth of children's length until 18 months of age compared with supplementation with either vitamin A + Zn or Zn alone, but not compared with placebo. It had no effects on other anthropometric measures and did not reduce the prevalence of growth faltering. Future studies should duplicate these findings before recommendations can be made.

Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.

Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

Influence of l-carnitine on metabolism and performance of sows.

In recent years, l-carnitine has been used increasingly as a supplement in livestock animals. The present review gives an overview of the effects of dietary l-carnitine supplementation on the reproductive performance of sows. Results concerning the effect of l-carnitine supplementation during pregnancy on litter sizes are controversial. There are some studies reporting an increased number of piglets born alive per litter, while others could not find such an effect. In contrast, most studies performed show consistently that l-carnitine supplementation to a sow diet low in native carnitine during gestation increases piglet and litter weights at birth and enhances growth of litters during the suckling period. Biochemical mechanisms underlying the favourable effect of carnitine on intra-uterine growth have not been fully elucidated. There is, however, some evidence that carnitine influences the insulin-like growth factor-axis in sows and leads to greater placentae, which in turn improves intra-uterine nutrition, and stimulates oxidation of glucose in the fetuses. These effects may, at least in part, be responsible for higher birth weights of piglets. The stimulating effect of carnitine on growth of the litters might be due to an improved suckling behaviour of piglets born to l-carnitine-supplemented sows, causing the sows' milk production to rise. In conclusion, recent studies have clearly shown that dietary l-carnitine supplementation increases the reproductive performance of sows. These findings suggest that endogenous de novo synthesis of carnitine is insufficient to meet the metabolic requirement of sows during gestation.

Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews.

Abundant data are now available to evaluate relationships between seafood consumption in pregnancy and childhood and neurocognitive development. We conducted two systematic reviews utilizing methodologies detailed by the Dietary Guidelines for Americans Scientific Advisory Committee 2020-2025. After reviewing 44 publications on 106,237 mother-offspring pairs and 25,960 children, our technical expert committee developed two conclusion statements that included the following: "Moderate and consistent evidence indicates that consumption of a wide range of amounts and types of commercially available seafood during pregnancy is associated with improved neurocognitive development of offspring as compared to eating no seafood. Overall, benefits to neurocognitive development began at the lowest amounts of seafood consumed (∼4 oz/wk) and continued through the highest amounts, above 12 oz/wk, some range up to >100 oz/wk.", "This evidence does not meet the criteria for "strong evidence" only due to a paucity of randomized controlled trials that may not be ethical or feasible to conduct for pregnancy" and "Moderate and consistent evidence indicates that consumption of >4 oz/wk and likely >12 oz/wk of seafood during childhood has beneficial associations with neurocognitive outcomes." No net adverse neurocognitive outcomes were reported among offspring at the highest ranges of seafood intakes despite associated increases in mercury exposures. Data are insufficient for conclusive statements regarding lactation, optimal amounts, categories or specific species characterized by mercury content and neurocognitive development; although there is some evidence that dark/oily seafood may be more beneficial. Research was conducted in healthy women and children and is generalizable to US populations. Assessment of seafood as a whole food integrates inherently integrates any adverse effects from neurotoxicants, if any, and benefits to neurocognition from omega-3 fats, as well as other nutrients critical to optimal neurological development. Understanding of the effects of seafood consumption on neurocognition can have significant public health implications.

An abundance of seafood consumption studies presents new opportunities to evaluate effects on neurocognitive development.

The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.

Impact of PUFA on early immune and fetal development.

It has recently been reported that the increased prevalence in childhood allergy may be linked to deviations in fetal immune development. One reason may be impaired nutrient supply. Hence, a well-differentiated placenta together with an optimal fetal nutrition via the mother are important prerequisites for the establishment of a functional immune system with normal immune responses. Fatty acids and their derivatives can influence both the early immune development and immune maturation by regulating numerous metabolic processes and the gene expression of important proteins such as enzymes and cytokines. The present review summarises the impact of nutritional fatty acids on the development of the immune system as well as the fetal development. It describes the mechanisms of action of PUFA, trans fatty acids and conjugated linoleic acids in programming the fetus with regard to its risk of acquiring atopic diseases in childhood.

Prenatal supplementation with multivitamins and the incidence of pediatric cancers: clinical and methodological considerations.

Cancer is the second leading cause of death in children. Research has been undertaken to identify risk factors associated with pediatric cancers. Nevertheless one single cause has not been isolated. Recent studies have suggested that prenatal multivitamin consumption may be associated with the prevention of pediatric cancers. It has been shown previously that prenatal multivitamin ingestion is associated with a decrease in congenital anomalies. The following review summarizes the available knowledge associating prenatal multivitamin consumption with the prevention of pediatric cancers.

Effect of a low-protein diet during pregnancy on skeletal muscle mechanical properties of offspring rats.

OBJECTIVE: The main goal of the present study was to investigate the effects of a low-protein diet during gestation on the biomechanical properties of skeletal muscle of offspring rats. METHODS: Male Wistar rats were divided into two groups according to their mothers' diet during pregnancy: a control group (mothers fed with 17% protein) and a low-protein group (mothers fed with 7.8% protein; UN). At birth, all mothers received a standardized meal ad libitum. When the rats were 25 and 90 d old, the soleus and extensor digitorum longus (EDL) muscles were removed from the pups. An analysis of the contractile and series elastic component properties was carried out on both muscles. Histochemical analysis was likewise performed. RESULTS: Group UN presented muscle wasting and diminution of maximum twitch and tetanic tension on the muscle at 25 and 90 d of life. There was an increase in maximal shortening velocity in the soleus and EDL muscles at 25 and 90 d in group UN. Series elastic component stiffness was increased in the soleus muscle, although a diminution of series elastic component stiffness was observed in the EDL at 25 d. With regard to the analysis of the muscle fiber proportions at 25 and 90 d, the UN group presented an increase in the IIa fibers in the soleus, whereas there was an increase in the IIb fibers and a diminution in the IIa fibers in the EDL. CONCLUSION: Low-protein intake during a critical period of development induces changes in the structure and function of skeletal muscle. Such changes may compromise an animal's posture and locomotion.

Red blood cell metallothionein as an indicator of zinc status during pregnancy.

OBJECTIVE: We describe the levels and patterns of change in red blood cell (RBC) metallothionein (MT) during pregnancy and the neonate and relate RBCMT to other indicators of zinc and iron status. METHODS: As part of a double-masked controlled trial of prenatal zinc supplementation among 242 Peruvian pregnant women, we determined RBCMT at enrollment (10-16 wk), at 28 and 36 wk of gestation, and in the cord blood at delivery in 158 women (86 who received daily supplements containing 60 mg of iron and 250 microg of folic acid and 72 whose supplements also contained 25 mg of zinc). In addition, we measured plasma and urinary zinc concentrations, hemoglobin and serum ferritin, and, on a limited sample, RBC zinc and placental MT. RESULTS: RBCMT increased during pregnancy, and levels in the cord blood approximated maternal values at 36 wk. Only RBC zinc at 36 wk differed by supplement type (P < 0.05). Increases in RBCMT over pregnancy were, however, related to early pregnancy RBC zinc and inversely with the decline in plasma zinc from baseline to 36 wk of gestation. CONCLUSION: Changes in RBCMT throughout pregnancy were consistent with the hypothesized role of MT in regulating zinc homeostasis. RBCMT appears to not be responsive during pregnancy to changes in zinc status achieved with supplements.