Maternal Tissues Research Articles

Environmental Nanoparticles Reach Human Fetal Brains.

Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8–15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8–15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences.

Short Term Changes in Dietary Fat Content and Metformin Treatment During Lactation Impact Milk Composition and Mammary Gland Morphology.

Maternal health and diet can have important consequences for offspring nutrition and metabolic health. During lactation, signals are communicated from the mother to the infant through milk via macronutrients, hormones, and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring weaning. We found that lactational HFD increased maternal adipose tissue weight, mammary gland adipocyte size, and altered milk lipid composition causing a higher amount of omega-6 (n6) long chain fatty acids and lower omega-3 (n3). Offspring of HFD dams were heavier with more body fat during suckling. Metformin (Met) exposure decreased maternal blood glucose and several milk amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin than HFD, but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to rescue the offspring from the effects of a maternal HFD during lactation.

Structure and permeability of the egg capsule of the placental Australian sharpnose shark, Rhizoprionodon taylori

Shark placentae are derived from modifications to the fetal yolk sac and the maternal uterine mucosa. In almost all placental sharks, embryonic development occurs in an egg capsule that remains intact for the entire pregnancy, separating the fetal tissues from the maternal tissues at the placental interface. Here, we investigate the structure and permeability of the egg capsules that surround developing embryos of the placental Australian sharpnose shark (Rhizoprionodon taylori) during late pregnancy. The egg capsule is an acellular fibrous structure that is 0.42 ± 0.04 μm thick at the placental interface between the yolk sac and uterine tissues, and 0.67 ± 0.08 μm thick in the paraplacental regions. This is the thinnest egg capsule of any placental shark measured so far, which may increase the diffusion rate of respiratory gases, fetal wastes, water and nutrients between maternal and fetal tissues. Molecules smaller than or equal to ~ 1000 Da can diffuse through the egg capsule, but larger proteins (~ 3000–26,000 Da) cannot. Similar permeability characteristics between the egg capsule of R. taylori and other placental sharks suggest that molecular size is an important determinant of the molecules that can be exchanged between the mother and her embryos during pregnancy.

Human milk fatty acid composition and its association with maternal blood and adipose tissue fatty acid content in a cohort of women from Europe

PurposeHuman milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated.Methods223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother’s blood and cord blood were established.ResultsDuring lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy.ConclusionsThese data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.

Fetal Membranes Contribute to Drug Transport across the Feto-Maternal Interface Utilizing the Breast Cancer Resistance Protein (BCRP).

During pregnancy, the placenta is established as a primary organ for drug transport at the maternal-fetal interface. The fetal membranes (FM) also form an interface with maternal tissues; however, their role in drug transport has not been previously investigated. Knowledge of drug transport across this feto-maternal interface along with the placenta can improve new drug development and testing for use during pregnancy. We also hypothesize that extracellular vesicles (exosomes 30–160 nm) released from the FM and placental cells may also contain drug transport proteins and might impact drug trafficking across the feto-maternal interfaces. The objectives were to (1) localize the breast cancer resistance protein (BCRP) in human FM; (2) determine the drug transport function of BCRP in chorion trophoblast cells (CTCs) of the FM; and (3) investigate the presence of BCRP in FM cell-derived exosomes, as a paracrine modifier of the tissue environment for transport functions. The gene and protein expressions of ABCG2/BCRP in FMs were determined by quantitative real-time PCR (qRT-PCR) and western blotting (WB) and were localized by immunohistochemistry (IHC). The surface expression of BCRP in FM cells was determined by flow cytometry. The functional role of BCRP was assessed by an EFFLUX dye multidrug resistance assay. The presence of BCRP in exosomes derived from CTCs and BeWo cells was examined using ExoView®. Data derived from CTCs are compared with placental trophoblast cells (BeWo). BCRP is expressed and localized in the fetal membrane, primarily in the chorion trophoblast cell layer and scarcely in the amnion epithelial layer (AEC), and primarily localized on both AEC and CTC cell surfaces. Efflux assay data showed that FM cells have similar drug resistance activity as BeWo cells, suggesting that FM also have drug transportation capabilities. BeWo- and CTC-derived exosomes expressed limited BCRP protein on the surface, so it was predominantly contained in the exosomal lumen. As far as we are aware, this is the first study to report BCRP expression in fetal membrane cells and as cargo in fetal membrane-derived exosomes. We report that fetal membrane cells are capable of drug transportation. Based on these results, investigational drug trials should include the FM and its exosomes as possible drug transportation routes in pregnancy.

Prediction of Maternal and Fetoplacental Concentrations of Cefazolin, Cefuroxime, and Amoxicillin during Pregnancy Using Bottom-Up Physiologically Based Pharmacokinetic Models.

Concerns over maternal and fetal drug exposures highlight the need for a better understanding of drug distribution into the fetus through the placental barrier. This study aimed to predict maternal and fetal drug disposition using physiologically based pharmacokinetic (PBPK) modeling. The detailed maternal-placental-fetal PBPK model within the Simcyp Simulator V20 was used to predict the maternal and fetoplacental exposure of cefazolin, cefuroxime, and amoxicillin during pregnancy and at delivery. The mechanistic dynamic model includes physiologic changes of the maternal, fetal, and placental parameters over the course of pregnancy. Placental kinetics were parametrized using permeability parameters determined from the physicochemical properties of these compounds. Then, the PBPK predictions were compared with the observed data. Fully bottom-up fetoplacental PBPK models were developed for cefuroxime, cefazolin, and amoxicillin without any parameter fitting. Predictions in nonpregnant subjects and in pregnant subjects fall within 2-fold of the observed values. Predictions matched observed pharmacokinetic data reported in nine maternal (five fetoplacental) studies for cefuroxime, 10 maternal (five fetoplacental) studies for cefazolin, and six maternal (two fetoplacental) studies for amoxicillin. Integration of the fetal and maternal system parameters within PBPK models, together with compound-related parameters used to calculate placental permeability, facilitates and extends the applications of the maternal-placental-fetal PBPK model. The developed model can also be used for designing clinical trials and prospectively used for maternal-fetal risk assessment after maternally administered drugs or unintended exposure to environmental toxicants. SIGNIFICANCE STATEMENT: This study investigates the performance of an integrated maternal-placental-fetal PBPK model to predict maternal and fetal tissue exposure of renally eliminated antibiotics that cross the placenta through a passive diffusion mechanism. The transplacental permeability clearance was predicted from the drug physicochemical properties. Results demonstrate that the PBPK approach can facilitate the prediction of maternal and fetal drug exposure simultaneously at any gestational age to support its use in the maternal-fetal exposure assessments.

A mitochondrial ADXR–ADX–P450 electron transport chain is essential for maternal gametophytic control of embryogenesis in Arabidopsis

Mitochondrial adrenodoxins (ADXs) are small iron-sulfur proteins with electron transfer properties. In animals, ADXs transfer electrons between an adrenodoxin reductase (ADXR) and mitochondrial P450s, which is crucial for steroidogenesis. Here we show that a plant mitochondrial steroidogenic pathway, dependent on an ADXR-ADX-P450 shuttle, is essential for female gametogenesis and early embryogenesis through a maternal effect. The steroid profile of maternal and gametophytic tissues of wild-type (WT) and adxr ovules revealed that homocastasterone is the main steroid present in WT gametophytes and that its levels are reduced in the mutant ovules. The application of exogenous homocastasterone partially rescued adxr and P450 mutant phenotypes, indicating that gametophytic homocastasterone biosynthesis is affected in the mutants and that a deficiency of this hormone causes the phenotypic alterations observed. These findings also suggest not only a remarkable similarity between steroid biosynthetic pathways in plants and animals but also a common function during sexual reproduction.

Differential Influx of Natural Plant Growth Regulators during Embryogeny in the Recalcitrant Seeds of Syzygium cumini (L) Skeels

Background: The hormonal up-regulation and down-regulation in recalcitrant seeds, on the other hand, has received little research. We tested fou plant growth regulators from distinct families of phytohormones at the same time to better understand their differential input from maternal tissues to growing Syzygium cumini seeds. Methods: During April-June 2020, seeds were collected in their native habitats in the Western Ghats. Seeds were chosen at random from each treatment. The embryonic tissues of seeds were chopped up and frozen for LC-MS/MS hormonal profiling. Result: Except for ABA, the dynamics of key plant hormones in this recalcitrant seed were identical to that of desiccation-tolerant orthodox seeds. When compared to other conventional seeds, SA was shown to accumulate at an unusually high level in mature embryonic tissues, demonstrating the highly hydrated seed’s defense mechanism against fungal attack following seed shedding.

Association between plasma leptin and cesarean section after induction of labor: a case control study

BackgroundObesity in pregnancy is common, with more than 50% of pregnant women being overweight or obese. Obesity has been identified as an independent predictor of dysfunctional labor and is associated with increased risk of failed induction of labor resulting in cesarean section. Leptin, an adipokine, is secreted from adipose tissue under the control of the obesity gene. Concentrations of leptin increase with increasing percent body fat due to elevated leptin production from the adipose tissue of obese individuals. Interestingly, the placenta is also a major source of leptin production during pregnancy. Leptin has regulatory effects on neuronal tissue, vascular smooth muscle, and nonvascular smooth muscle systems. It has also been demonstrated that leptin has an inhibitory effect on myometrial contractility with both intensity and frequency of contractions decreased. These findings suggest that leptin may play an important role in dysfunctional labor and be associated with the outcome of induction of labor at term. Our aim is to determine whether maternal plasma leptin concentration is indicative of the outcome of induction of labor at term. We hypothesize that elevated maternal plasma leptin levels are associated with a failed term induction of labor resulting in a cesarean delivery.MethodsIn this case-control study, leptin was measured in 3rd trimester plasma samples. To analyze labor outcomes, 174 women were selected based on having undergone an induction of labor (IOL), (115 women with successful IOL and 59 women with a failed IOL). Plasma samples and clinical information were obtained from the UI Maternal Fetal Tissue Bank (IRB# 200910784). Maternal plasma leptin and total protein concentrations were measured using commercially available assays. Bivariate analyses and logistic regression models were constructed using regression identified clinically significant confounding variables. All variables were tested at significance level of 0.05.ResultsWomen with failed IOL had higher maternal plasma leptin values (0.5 vs 0.3 pg, P = 0.01). These women were more likely to have obesity (mean BMI 32 vs 27 kg/m2, P = 0.0002) as well as require multiple induction methods (93% vs 73%, p = 0.008). Logistic regression showed Bishop score (OR 1.5, p < 0.001), BMI (OR 0.92, P < 0.001), preeclampsia (OR 0.12, P = 0.010), use of multiple methods of induction (OR 0.22, P = 0.008) and leptin (OR 0.42, P = 0.017) were significantly associated with IOL outcome. Specifically, after controlling for BMI, Bishop Score, and preeclampsia, leptin was still predictive of a failed IOL with an odds ratio of 0.47 (P = 0.046). Finally, using leptin as a predictor for fetal outcomes, leptin was also associated with of fetal intolerance of labor, with an odds ratio of 2.3 (P = 0.027). This association remained but failed to meet statistical significance when controlling for successful (IOL) (OR 1.5, P = 0.50).ConclusionsMaternal plasma leptin may be a useful tool for determining which women are likely to have a failed induction of labor and for counseling women about undertaking an induction of labor versus proceeding with cesarean delivery.

Analytical Detection of Prenatal Drug Exposure in Early Childhood in Prenatal, Perinatal and Postnatal Matrices

Currently, there are few validated and standardized tests for drug screening in pregnant women. In these as-says, maternal and fetal tissues are taken for screening, including maternal and fetal blood, meconium, hair, urine, pieces of placental material, and umbilical cord. Screening methods use different techniques including enzyme-linked immunosorbent assays, spectrometry, gas chromatography, high-performance liquid chromatography coupled with other detection techniques such as mass spectrometry. Here a new method is described that detects qualitative medication, legal drugs and illicit drugs in prenatal, perinatal and postnatal matrices in order to elucidate and explain various disorders in early childhood such as neonatal abstinence syndrome. Important in this work was the question of the range and sensitivity of methods to detect the sub-stances.

Study on the Correlation between the Levels of HtrA3 and TGF-β2 in Late Pregnancy and Preeclampsia.

Preeclampsia (PE) is a common and proprietary complication during pregnancy. The correlation was found between the levels of HtrA3 and TGF-β 2 and preeclampsia (PE). This study aimed to detect the HtrA3 and TGF-β2 in different parts of the third trimester (maternal serum, placenta). The 102 pregnant women who were eligible for enrollment in the obstetric examination at Tengzhou Maternity and Child Health Hospital from June 2020 to December 2020 were selected as the research objects. 28 cases diagnosed with PE were set up as the observation group 1, and 24 cases diagnosed with severe PE were set up as the observation group 2. Select 50 normal pregnant women as the control group and research the expressions of HtrA3 and TGF-β2 in maternal blood and placental tissues of patients with PE. ELISA was used to measure the concentration of HtrA3 and TGF-β2 in maternal blood. The distribution of HtrA3 and TGF-β2 in the placenta was observed by immunohistochemical techniques (IHC) and mean optical density value (MOD). S/D was measured by using color Doppler ultrasonic. The concentration of HtrA3 and TGF-β2 in the maternal blood and placenta tissue was higher in severe PE compared with PE and normotensive pregnancy, respectively (P < 0.05). There is a negative correlation between the level of HtrA3 and TGF-β2 and the birthweight of newborns both in maternal plasma and placenta tissue in preeclampsia and positive correlation between HtrA3 and TGF-β2 levels and S/D. HtrA3 and TGF-β2 may correlate with severity of PE and their neonatal adverse outcomes.

Maternal high-fat diet programs white and brown adipose tissue lipidome and transcriptome in offspring in a sex- and tissue-dependent manner in mice

ObjectiveThe prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring.MethodsMice dam were fed either a control diet or a high-fat diet (HFD) for 6-week prior mating and continued their respective diet during gestation and lactation. At weaning, female and male offspring were fed the HFD until sacrifice. White (WAT) and brown (BAT) adipose tissues were investigated in vivo by nuclear magnetic resonance at two different timepoints in life (midterm and endterm) and tissues were collected at endterm for lipidomic analysis and RNA sequencing. We explored the sex-dependent metabolic adaptation and gene programming changes by maternal HFD in visceral AT (VAT), subcutaneous AT (SAT) and BAT of offspring.ResultsWe show that the triglyceride profile varies between adipose depots, sexes and maternal diet. In female offspring, maternal HFD remodels the triglycerides profile in SAT and BAT, and increases thermogenesis and cell differentiation in BAT, which may prevent metabolic complication later in life. Male offspring exhibit whitening of BAT and hyperplasia in VAT when born from high-fat mothers, with impaired metabolic profile. Maternal HFD differentially programs gene expression in WAT and BAT of female and male offspring.ConclusionMaternal HFD modulates metabolic profile in offspring in a sex-dependent manner. A sex- and maternal diet-dependent gene programming exists in VAT, SAT, and BAT which may be key player in the sexual dimorphism in the metabolic adaptation later in life.

Galea spixii embryos have potential to produce steroid hormones.

Estrogens and progestogens are hormones produced by maternal organs and it is required for recognition and maintenance of pregnancy. In addition, the embryo may also be a source. For this, the aim was to identify steroidogenic expression on Galea spixii embryos early in the embryonic period. Embryos were collected on Days 10 and 15 of gestation; some were fixed in 4% paraformaldehyde for morphological and immunohistochemical analysis (P450arom), whereas others had RNA extracted to determine presence of CYP19a1 gene. In addition, for immunochemistry, maternal ovaries were collected as positive control tissues. Maternal tissues had positive staining for aromatase, whereas none of the embryos stained for P450 aromatase. Based on qPCR reactions, CYP19a1 gene were expressed in all embryos. Galea spixii embryos expressed steroidogenic genes during the post-implantation period, indicating they have the potential to produce steroid hormones.

Parental regulation of seed development

Angiosperms produce seeds with two zygotic tissues, namely the embryo and endosperm, from a unique double fertilization process. Seed development occurs within the maternal tissue and relies on maternal resources. Paternal tissue is not directly involved in seed development, and paternal regulation is usually based on the paternal genome of zygotic tissues in the filial generation. The complicated maternal-paternal communications and maternal-zygotic interactions result in distinguishable genetic effects on seed development. Here we review the conceptual framework of parental regulations on seed development. We summarize the common seed development process and look into the regulations pertaining to maternal and zygotic effects. Examples with more complicated interactions at the inter-tissue level are also discussed in the context of interwoven parental regulations.

Effect Study of Physiological changes of a Pregnant Woman

Understating these changes and their profound impact on the pharmacokinetic properties of drugs in pregnancy isessential to optimize maternal and fetal health. During normal pregnancy, the renin–angiotensin system (RAS) plays avitally important role in salt balance and subsequent well-being of mother and fetus. In this balance, one must consider notonly the classical renal RAS but also that of the uteroplacental unit, where both maternal and fetal tissues contribute to thesignaling cascade. Many studies have shown that in normal pregnancy there is an increase in almost all of the componentsof the RAS. In derangements of pregnancy this delicate equilibrium can become unbalanced. Preeclampsia is one suchcase. It is a disorder of pregnancy characterized by hypertension, proteinuria and placental abnormalities associated withshallow trophoblast invasion and impaired spiral artery remodeling. Changes in the cardiovascular system in pregnancyare profound and begin early in pregnancy, such that by eight weeks’ gestation, the cardiac output has already increasedby 20%. The primary event is probably peripheral vasodilatation. This is mediated by endothelium-dependent factors,including nitric oxide synthesis, upregulated by oestradiol and possibly vasodilatory prostaglandins (PGI2). There is asignificant increase in oxygen demand during normal pregnancy. This is due to a 15% increase in the metabolic rate anda 20% increased consumption of oxygen.

Effects of porcine reproductive and respiratory syndrome virus (PRRSV) on thyroid hormone metabolism in the late gestation fetus

Porcine reproductive and respiratory syndrome virus (PRRSV) in late gestation causes a profound suppression of circulating maternal and fetal thyroid hormone during a critical window of development. To understand this relationship, we evaluated thyroid hormone metabolism at the maternal–fetal interface and within fetal tissues, along with hormone metabolite levels in serum. Fetuses were classified using an established model based on viral load in serum and thymus, and preservation status, including uninfected (UNIF), high-viral load viable (HV-VIA), and high-viral load meconium-stained (HV-MEC), with additional controls from sham-inoculated gilts (CON). Expression of three iodothyronine deiodinases, five sulfotransferases, sulfatase, and two solute carriers known to transport thyroid hormone were evaluated in maternal endometrium and fetal placenta, liver, and kidney. Serum thyroxin (T4), reverse triiodothyronine (rT3), and diiodothyronine (T2) were evaluated via liquid chromatography tandem mass spectrometry. Significant changes in gene expression were observed in all four tissues, with the liver being the most severely impacted. We observed local and fetal specific regulation of maternal tissues through significant upregulation of DIO2 and DIO3 expression in the endometrium corresponding to infected but viable fetuses relative to uninfected and control fetuses. Expression levels of DIO2 and DIO3 were significantly higher in the resilient (HV-VIA) fetuses relative to the susceptible (HV-MEC) fetuses. A substantial decrease in serum T4 was confirmed, with no corresponding increase in rT3 or T2. Collectively, these results show that thyroid hormone metabolism is altered at the maternal–fetal interface and within the PRRSV infected fetus and is associated with fetal viability.

Role of Folate and Folic Acid During Pregnancy

Abstract: Pregnancy represents a period of fast tissue growth of maternal and foetal tissues that's related to enhanced energy and nutrient needs. Maternal nutrition throughout gestation period, has being essential for best offspring development, reducing long unwellness burden and for general health throughout life. Maternal Folate throughout pregnancy might have numerous roles in offspring health, as well as neurodevelopment and psychological feature performance in childhood. Folate is crucial for C1 metabolism, a network of pathways concerned in many biological processes as well as nucleotide synthesis, deoxyribonucleic acid repair and methylation reactions. The periconceptional use of pteroylglutamic acid (Folic Acid ) containing supplements reduces the primary incidence, as well as recurrence of neural tube defects. Folic Acid (FA) are artificial form of a necessary vitamin generically considered Folates or B9. It is concerned in one-carbon metabolism, and it's been connected to lowering neural tube Defect (NTD). National programs to mandate fortification of food with Folic Acid have reduced the prevalence of NTDs worldwide . The indisputable protecting role of Folic Acid in the hindrance of NTD, in addition to the low compliance of women to Folic Acid recommendations, has aroused the choice of mandatory Folic Acid fortification, a policy currently in place in over eighty countries worldwide. Mandatory food fortification needs food makers to feature Folic Acid to certain foods (e.g. starch or grain products), whereas voluntary fortification permits Folic Acid to be added to foods at the discretion of manufacturers. Food fortification with Folic Acid because the intervention is likely to achieve increasing Folic Acid intake among populations throughout the world. The objective of this article is to discuss the Role of Folic Acid and Folate during pregnancy and to review the role of Folate and Folic Acid , metabolism , absorption and Folic Acid effects on maternal on the basis of recent findings that are important for implementation of fortified food to design future studies. Keywords: Neurodevelopment, Methylation Reactions, Pteroylglutamic Acid, Bioavailability, Monoglutamates.

Nutrition of Pregnant and Lactating Women in the First 1000 Days of Infant

Nutrition for pregnant and breastfeeding women is fundamental to the development of the child in its first 1000 days and beyond. To evaluate the adequacy of this nutrition, we have relied on historical dietary surveys and on personal French studies (4 studies from 1997 to 2014) involving dietary surveys over 3 days (3D-Diet). Furthermore, our team specialized in lipids has measured the fatty acids of breast milk, which reflect the dietary intake of lipids, from breast milk (1997–2014) and from the lipids of cord blood and maternal fat tissue, in 1997. According to our results, pregnancy needs require an additional 300 Kcal, but surveys show a bad equilibrium of macronutrients: an excess of proteins of fetus [17% of total energy intake (TEI) vs. 15%], excess of fats (45% vs. 35%), excess of saturated fatty acids (SFA), not enough polyunsaturated fatty acids (PUFA), particularly omega 3, and a deficit in carbohydrates (45% vs. 55%). There is also a deficiency in calcium, iron, magnesium, zinc, and vitamins D, B6, B5, and folates. Breast milk adequately provides all the macronutrients necessary for the growth of the child. Proteins and carbohydrates vary little according to the mother’s diet; on the other hand, its composition in lipids, trace elements, and vitamins is highly variable with the mother’s diet of breast milk. In our study in 2014, in 80 participants, the diet was low in calories (1996 Kcal vs. 2200 Kcal RDA), normoprotidic, normolipidic, but low in carbohydrate, especially polysaccharides. We note a very insufficient intake of fish and dairy products, and therefore calcium, but also magnesium, zinc, iron, and vitamins D, E, B6, and folate. Consequently, if the mother does not achieve a diet adequate to her needs during pregnancy and breastfeeding, it will be necessary to resort to medicinal supplements in minerals, trace elements, vitamins, and omega 3.

Dietary N-carbamylglutamate or L-arginine improves fetal intestinal amino acid profiles during intrauterine growth restriction in undernourished ewes.

Our previous studies demonstrated that prenatal in utero growth restriction impairs postnatal intestinal function. Thus, improving postpartal intestinal absorption capacity and growth by manipulating the maternal diet prepartum is of importance. This work was conducted to determine whether supplementation of N-carbamylglutamate (NCG) or rumen-protected L-arginine (RP-Arg) increased fetal intestinal amino acid (AA) profiles in intrauterine growth retardation (IUGR) fetuses. On d 35 of gestation, Hu ewes (n = 32) carrying twin fetuses were randomized into 4 groups (8 ewes and 16 fetuses in each group), where diets were as follows: 100% of nutrient requirements recommended by National Research Council (NRC, 2007) (CON); 50% of nutrient requirements recommended by NRC (2007) (RES); RES + RP-Arg (20 g/d), (RES + ARG); and RES + NCG (5 g/d), (RES + NCG). On d 110 of gestation, both fetal and maternal tissues were collected and weighed. Compared with RES, solute carrier family 1, member 5 (SLC1A5) was upregulated (P < 0.05) within fetal jejunum, duodenum and ileum when supplementing NCG and RP-Arg. Relative to RES, RP-Arg or NCG supplementation to RES resulted in upregulation (P < 0.05) of peptide transporter 1 protein abundance within the fetal ileum. NCG or RP-Arg supplementation to RES also upregulated phosphorylated mechanistic target of rapamycin (pmTOR)-to-mTOR ratio in the fetal ileum induced by IUGR (P < 0.05). As a result, during IUGR, supplementation of Arg or NCG affected intestinal AA profiles in the fetus in part through controlling mTOR signal transduction as well as AA and peptide transport. Future studies should be conducted to understand the role (if any) of the placenta on the improvement of growth and AA profiles independent of the fetal intestine. This would help demonstrate the relative contribution of intestinal uptake in fetal life.

Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health.

Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.