Implications For Fetal Growth Research Articles

Serum levels of perchlorate and chlorate in pregnant women from south China and the related health risk with thyroid function

Perchlorate and chlorate are recognized as ubiquitously inorganic pollutants inenvrionment owing to their high solubility in water and resistance to degradation. Previous studies have confirmed the potential adverse effects of perchlorate and chlorate on human thyroid function, along with implications for fetal growth and development. The fetus grows and develops pregnant women's womb and absorbs nutrients from her body. However, there is still limited information on prenatal exposure to perchlorate and chlorate and the related health risks, especially in China. In this study, a total of 430 serum specimens obtained from pregnant females residing in Southern China were analyzed to ascertain the levels of perchlorate and chlorate, and explore the relationship between perchlorate and chlorate and thyroid function by linear regression, WQS, and QGC. The measured serum levels of perchlorate and chlorate were comparatively elevated, demonstrating median values of 0.693 μg/L and 1.36 μg/L, respectively. The estimated exposure dose of perchlorate in 19.7% of pregnant women exceeded the USEPA reference dose, indicating potential health risks. Although no significant association was found between serum perchlorate and thyroid hormone levels, the exposure to perchlorate for pregnant women in Southern China is cause for concern given their sensitivity to chemicals during pregnancy and the relatively high internal exposure levels.

Placental Cell Type Specific Transcriptional Responses to Maternal Obesity: Implications for Fetal Growth

Placental Cell Type Specific Transcriptional Responses to Maternal Obesity: Implications for Fetal Growth

Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health

Prenatal exposure to phthalates negatively affects the offspring's health. In particular, epigenetic alterations, such as DNA methylation, may connect phthalate exposure with health outcomes. Here, we evaluated the association of di-2-ethylhexyl phthalate (DEHP) exposure in utero with cord blood epigenome-wide DNA methylation in 203 mother-child pairs enrolled in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analysis demonstrated the predominant positive associations between the levels of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), in maternal blood and DNA methylation levels in cord blood. The genes annotated to the CpGs positively associated with MEHP levels were enriched for pathways related to metabolism, the endocrine system, and signal transduction. Among them, methylation levels of CpGs involved in metabolism were inversely associated with the offspring's ponderal index (PI). Further, clustering and mediation analyses suggested that multiple increased methylation changes may jointly mediate the association of DEHP exposure in utero with the offspring's PI at birth. Although further studies are required to assess the impact of these changes, this study suggests that differential DNA methylation may link phthalate exposure in utero to fetal growth and further imply that DNA methylation has predictive value for the offspring's obesity.

Controlled elevated temperatures during early-mid gestation cause placental insufficiency and implications for fetal growth in pregnant pigs

It is known that pig offspring born from pregnant pigs exposed to elevated ambient temperatures during gestation have altered phenotypes, possibly due to placental insufficiency and impaired fetal growth. Therefore, the objective of this study was to quantify the effect of maternal heat exposure during early-mid gestation, when pig placentae grow heavily, on placental and fetal development. Fifteen pregnant pigs were allocated to thermoneutral (TN; 20 °C; n = 7) or cyclic elevated temperature conditions (ET; 28 to 33 °C; n = 8) from d40 to d60 of gestation. Following euthanasia of the pigs on d60, placental and fetal morphometry and biochemistry were measured. Compared to TN fetuses, ET fetuses had increased (P = 0.041) placental weights and a lower (P = 0.013) placental efficiency (fetal/placental weight), although fetal weights were not significantly different. Fetuses from ET pigs had reduced (P = 0.032) M. longissimus fibre number density and a thicker (P = 0.017) placental epithelial layer compared to their TN counterparts. Elevated temperatures decreased (P = 0.026) placental mRNA expression of a glucose transporter (GLUT-3) and increased (P = 0.037) placental IGF-2 mRNA expression. In conclusion, controlled elevated temperatures between d40 to d60 of gestation reduced pig placental efficiency, resulting in compensatory growth of the placentae to maintain fetal development. Placental insufficiency during early-mid gestation may have implications for fetal development, possibly causing a long-term phenotypic change of the progeny.

Placental transport of nutrients and its implications for fetal growth

Placental growth during early and mid-pregnancy has a powerful, constraining influence on fetal growth during late pregnancy. Studies involving surgical and environmental reduction of placental size in sheep have shown an associated reduction in capacity to transport oxygen, glucose and amino acids. Oxygen transport is limited by placental blood flow but transport of glucose and amino acids is determined by the abundance and activity of specific transport proteins. Glucose transporters include the GLUT1 and GLUT3 isoforms previously identified in brain and other tissues; systems for active transport of amino acids have been inferred but not characterized. Placental metabolism of glucose and amino acids has major effects both on the quantity of carbon and nitrogen delivered to the fetus, and on the composition of substrates involved. For example, the uteroplacental tissues consume more than 60% of uterine glucose uptake during late pregnancy, and the placenta substantially modifies the pattern of amino acids delivered to fetal blood. The placenta also participates in the array of metabolic adaptations of maternal and conceptus tissues to altered maternal nutrient supply. Placental capacity for glucose transport in moderately undernourished ewes is upregulated, partly by increased expression of the GLUT3 transport protein. During more severe glucose deprivation, placental transfer and fetal uptake of glucose are constrained in proportion with maternal supply, leading to fetal growth retardation.

Assessment of Maternal Vascular Remodeling During Pregnancy in the Mouse Uterus.

The placenta mediates the exchange of factors such as gases and nutrients between mother and fetus and has specific demands for supply of blood from the maternal circulation. The maternal uterine vasculature needs to adapt to this temporary demand and the success of this arterial remodeling process has implications for fetal growth. Cells of the maternal immune system, especially natural killer (NK) cells, play a critical role in this process. Here we describe a method to assess the degree of remodeling of maternal spiral arteries during mouse pregnancy. Hematoxylin and eosin-stained tissue sections are scanned and the size of the vessels analysed. As a complementary validation method, we also present a qualitative assessment for the success of the remodeling process by immunohistochemical detection of smooth muscle actin (SMA), which normally disappears from within the arterial vascular media at mid-gestation. Together, these methods enable determination of an important parameter of the pregnancy phenotype. These results can be combined with other endpoints of mouse pregnancy to provide insight into the mechanisms underlying pregnancy-related complications.

Assessment of Maternal Vascular Remodeling During Pregnancy in the Mouse Uterus

The placenta mediates the exchange of factors such as gases and nutrients between mother and fetus and has specific demands for supply of blood from the maternal circulation. The maternal uterine vasculature needs to adapt to this temporary demand and the success of this arterial remodeling process has implications for fetal growth. Cells of the maternal immune system, especially natural killer (NK) cells, play a critical role in this process. Here we describe a method to assess the degree of remodeling of maternal spiral arteries during mouse pregnancy. Hematoxylin and eosin-stained tissue sections are scanned and the size of the vessels analysed. As a complementary validation method, we also present a qualitative assessment for the success of the remodeling process by immunohistochemical detection of smooth muscle actin (SMA), which normally disappears from within the arterial vascular media at mid-gestation. Together, these methods enable determination of an important parameter of the pregnancy phenotype. These results can be combined with other endpoints of mouse pregnancy to provide insight into the mechanisms underlying pregnancy-related complications.

A role for delta-like homologue 1 in a secretory placental population and implications for fetal growth

A role for delta-like homologue 1 in a secretory placental population and implications for fetal growth

Commentary: One-carbon metabolism has major implications for fetal growth and development beyond neural tube defects.

a 56 -g reduction in birthweight of infants per standard deviation (SD) increase in homocysteine levels during pregnancy. However, a comparison of women in the lowest vs highest quartile for homcysteine suggests the potential for much greater effects (differences of 110–150 g). In addition, somewhat unusually, the estimates of the effect of maternal homocysteine on birthweight using a genetic proxy in the study by Yajnik and colleagues show a much stronger association (a reduction of about 250 g per SD of homocysteine) than the observational biomarker-birthweight association. This implies that the ‘real’ effect of one-carbon metabolism and its related nutrients (in the absence of confounding by other factors) is much greater than the 50 g reported, and is even greater that the difference in birthweight of offspring from smoking and non-smoking mothers (around 150 g to 200 g difference) 2 and suggests a key role of this pathway in fetal growth and development.

Lipid Metabolism During Pregnancy and its Implications for Fetal Growth

More glucose crosses the placenta than any other substrate, but correlations between its concentration in maternal plasma and fetal growth are not found consistently. The accumulation of maternal fat depots and hyperlipidemia are the two principal changes in lipid metabolism during pregnancy. Although lipids cross the placenta with difficulty, maternal plasma triacylglycerols (TAG) and non-esterified fatty acids (NEFA) correlate with fetal lipids, fetal growth and fat mass under certain conditions. In intrauterine growth restriction, impaired placental transfer of lipophilic compounds (long-chain polyunsaturated fatty acids and lipophilic vitamins) seems to underpin metabolic dysfunction and decreased birth weight. In gestational diabetes mellitus (GDM), maternal TAG and NEFA levels correlate with neonatal anthropometric measures. In GDM, adipocyte fatty acid-binding protein in fetuses correlated with neonatal fat mass; changes in maternal or cord blood leptin, retinol binding protein 4 and adiponectin concentrations have been related to neonatal fat mass or birth weight, although their importance remains to be investigated. The angiopoietin-like protein 4 (ANGPTL-4) is secreted from adipose tissue, liver and placenta, and irreversibly inhibits lipoprotein lipase (LPL) activity. Maternal plasma ANGPTL-4 is decreased in GDM, and it has been proposed to be responsible for an increase in placental LPL activity, which would facilitate a greater fatty acid placental transfer, contributing to the higher fetal fat accumulation. Thus, while evidence suggesting major involvement of maternal lipid metabolism in fetal adiposity and growth exists, the precise mechanisms remain to be elucidated.

Maternal micronutrients, omega-3 fatty acids, and placental PPARγ expression.

An altered one-carbon cycle is known to influence placental and fetal development. We hypothesize that deficiency of maternal micronutrients such as folic acid and vitamin B12 will lead to increased oxidative stress, reduced long-chain polyunsaturated fatty acids, and altered expression of peroxisome proliferator activated receptor (PPARγ) in the placenta, and omega-3 fatty acid supplementation to these diets will increase the expression of PPARγ. Female rats were divided into 5 groups: control, folic acid deficient, vitamin B12 deficient, folic acid deficient + omega-3 fatty acid supplemented, and vitamin B12 deficient + omega-3 fatty acid supplemented. Dams were dissected on gestational day 20. Maternal micronutrient deficiency leads to lower (p < 0.05) levels of placental docosahexaenoic acid, arachidonic acid, PPARγ expression and higher (p < 0.05) levels of plasma malonidialdehyde, placental IL-6, and TNF-α. Omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalized the expression of PPARγ and lowered the levels of placental TNF-α. In the case of supplementation to a folic acid deficient diet it lowered the levels of malonidialdehyde and placental IL-6 and TNF-α. This study has implications for fetal growth as oxidative stress, inflammation, and PPARγ are known to play a key role in the placental development.

Lifetime racism and blood pressure changes during pregnancy: Implications for fetal growth.

Research suggests that exposure to racism partially explains why African American women are 2 to 3 times more likely to deliver low birth weight and preterm infants. However, the physiological pathways by which racism exerts these effects are unclear. This study examined how lifetime exposure to racism, in combination with maternal blood pressure changes during pregnancy, was associated with fetal growth. African American pregnant women (n = 39) reported exposure to childhood and adulthood racism in several life domains (e.g., at school, at work), which were experienced directly or indirectly, meaning vicariously experienced when someone close to them was treated unfairly. A research nurse measured maternal blood pressure at 18 to 20 and 30 to 32 weeks gestation. Standardized questionnaires and trained interviewers assessed maternal demographics. Neonatal length of gestation and birth weight data were collected from medical charts. Childhood racism interacted with diastolic blood pressure to predict birth weight. Specifically, women with two or more domains of indirect exposure to racism in childhood and increases in diastolic blood pressure between 18 and 32 weeks had lower gestational age adjusted birth weight than the other women. A similar pattern was found for direct exposure to racism in childhood. Increases in diastolic blood pressure between the second and third trimesters predicted lower birth weight, but only when racism exposure in childhood (direct or indirect) was relatively high. Understanding pregnant African American women's lifetime direct and indirect experiences with racism in combination with prenatal blood pressure may improve identification of highest risk subgroups within this population.

Placental abruption and placental weight – implications for fetal growth

Placental abruption is associated with increased risks of preterm delivery and fetal growth restriction. As abruption is apparently a disease of the placenta, the extent to which abruption impacts the growth and development of the placenta remains poorly understood. We reasoned that a study of fetal growth and placental growth in relation to abruption might provide some clues to understanding the process through which placental abruption impacts fetal growth. Multicenter, prospective cohort study. USA, 1959-1966. A total of 38684 pregnancies resulting in singleton live births (22-44weeks). Risk ratio of placental ratio <10th centile for gestational age in relation to abruption. Placental ratio was defined as the difference between placental weight and birthweight divided by birthweight (and expressed per 100 births). Mean birthweight and placental weight were, on average, lower among abruption than nonabruption births, but this difference was observed only among births at <37weeks. Births with placental ratio <10th centile were lower among abruption than nonabruption births at 22-36weeks (risk ratio 0.4, 95% CI 0.2-0.8), but not at term (risk ratio 0.9, 95% CI 0.6-1.2). In normal pregnancies, fetal weight and placental weight may operate under independent mechanisms, but in the presence of abruption, the associations appear largely through an interaction of both the maternal and fetal environments. This study underscores the importance of examining both the maternal and fetal compartments - and their interactions - to fully understand the consequences of abruption on fetal growth impairment.

Environmental regulation of placental phenotype: implications for fetal growth

Environmental conditions during pregnancy determine birthweight, neonatal viability and adult phenotype in human and other animals. In part, these effects may be mediated by the placenta, the principal source of nutrients for fetal development. However, little is known about the environmental regulation of placental phenotype. Generally, placental weight is reduced during suboptimal conditions like maternal malnutrition or hypoxaemia but compensatory adaptations can occur in placental nutrient transport capacity to help maintain fetal growth. In vivo studies show that transplacental glucose and amino acid transfer adapt to the prevailing conditions induced by manipulating maternal calorie intake, dietary composition and hormone exposure. These adaptations are due to changes in placental morphology, metabolism and/or abundance of specific nutrient transporters. This review examines environmental programming of placental phenotype with particular emphasis on placental nutrient transport capacity and its implications for fetal growth, mainly in rodents. It also considers the systemic, cellular and molecular mechanisms involved in signalling environmental cues to the placenta. Ultimately, the ability of the placenta to balance the competing interests of mother and fetus in resource allocation may determine not only the success of pregnancy in producing viable neonates but also the long-term health of the offspring.

Proline metabolism in the conceptus: implications for fetal growth and development

Although there are published studies of proline biochemistry and nutrition in cultured cells and postnatal animals, little is known about proline metabolism and function in the conceptus (embryo/fetus, associated placental membranes, and fetal fluids). Because of the invasive nature of biochemical research on placental and fetal growth, animal models are often used to test hypotheses of biological importance. Recent evidence from studies with pigs and sheep shows that proline is a major substrate for polyamine synthesis via proline oxidase, ornithine aminotransferase, and ornithine decarboxylase in placentae. Both porcine and ovine placentae have a high capacity for proline catabolism and polyamine production. In addition, allantoic and amniotic fluids contain enzymes to convert proline into ornithine, which is delivered through the circulation to placental tissues. There is exquisite metabolic coordination among integrated pathways that support highest rates of polyamine synthesis and concentrations in placentae during early gestation when placental growth is most rapid. Interestingly, reduced placental and fetal growth are associated with reductions in placental proline transport, proline oxidase activity, and concentrations of polyamines in gestating dams with either naturally occurring or malnutrition-induced growth retardation. Conversely, increasing proline availability in maternal plasma through nutritional or pharmacological modulation in pigs and sheep enhances concentrations of proline and polyamines in placentae and fetal fluids, as well as fetal growth. These novel findings suggest an important role for proline in conceptus metabolism, growth and development, as well as a potential treatment for intrauterine growth restriction, which is a significant problem in both human medicine and animal agriculture.

Nitric oxide and superoxide impair human placental amino acid uptake and increase Na + permeability: implications for fetal growth

Based on evidence that thiol and tyrosine reagents inhibit some amino acid transporters, we tested the hypothesis that NO- and O 2 −-derived free radicals would impair nutrient uptake by the human placenta. Syncytiotrophoblast microvillous plasma membrane vesicles (MVM) and placental villous fragments were exposed to the drug SIN-1 in the presence or absence of superoxide dismutase (SOD) and hemoglobin (Hb). The uptake of [ 3H]arginine, [ 3H]taurine, and [ 3H]leucine; [ 14C]MeAIB; and 22Na was studied in MVM, whereas the uptake of [ 3H]taurine was examined in villous fragments. Nitrotyrosine formation was assessed by Western blotting and quantified by ELISA. In MVM, SIN-1 caused an inhibition of [ 3H]arginine, [ 3H]taurine, and [ 14C]MeAIB uptake but had no significant effect on equilibrium [ 3H]leucine uptake. These effects were prevented by SOD or Hb, implying that both NO and O 2 − radicals were essential. In contrast, 22Na + uptake was significantly increased, and this effect was prevented by SOD. In villous fragments, SIN-1 impaired Na +-dependent [ 3H]taurine uptake, with no effect on Na +-independent uptake. Increased nitrotyrosine formation was observed in MVM after SIN-1 treatment. Endogenous NO- and O 2 −-derived free radicals may alter human placental nutrient transfer in vivo, with implications for fetal growth.

Regulation of placental nutrient transport and implications for fetal growth

Fetal macronutrient requirements for oxidative metabolism and growth are met by placental transport of glucose, amino acids, and, to a lesser extent that varies with species, fatty acids. It is becoming possible to relate the maternal-fetal transport kinetics of these molecules in vivo to the expression and distribution of specific transporters among placental cell types and subcellular membrane fractions. This is most true for glucose transport, although apparent inconsistencies among data on the roles and relative importance of the predominant placenta glucose transporters, GLUT-1 and GLUT-3, remain to be resolved. The quantity of macronutrients transferred to the fetus from the maternal bloodstream is greatly influenced by placental metabolism, which results in net consumption of large amounts of glucose and, to a lesser extent, amino acids. The pattern of fetal nutrient supply is also altered considerably by placental conversion of glucose to lactate and, in some species, fructose, and extensive transamination of amino acids. Placental capacity for transport of glucose and amino acids increases with fetal demand as gestation advances through expansion of the exchange surface area and increased expression of specific transport molecules. In late pregnancy, transport capacity is closely related to placental size and can be modified by maternal nutrition. Preliminary evidence suggests that placental expression and function of specific transport proteins are influenced by extracellular concentrations of nutrients and endocrine factors, but, in general, the humoral regulation of placental capacity for nutrient transport is poorly understood. Consequences of normal and abnormal development of placental transport functions for fetal growth, especially during late gestation, and, possibly, for fetal programming of postnatal disorders, are discussed.