Maternal Diet High in Linoleic Acid Alters Renal Branching Morphogenesis and mTOR/AKT Signalling Genes in Rat Fetal Kidneys.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis Ret and Gdnf in offspring, independent of sex. Furthermore, downstream targets of megalin, namely mTOR, Akt3 and Prkab2, were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target Gfra1 in females (p = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.

Janus kinase-signal transducer and activator of transcription signaling pathway in the ocular cells of rat fetuses exposed to maternal saturated fat ingestion.

OBJECTIVE: The aim of this study was to analyze possible alterations (morphological and inflammatory) in the ocular cells of fetuses from mothers with insulin resistance exposed to saturated fatty acids through the period of pregnancy. METHODS: Wistar female rats were induced to develop insulin resistance before pregnancy. Fetuses' skulls were collected on the 20th day of intrauterine life. The rats were separated on the first day of management into two groups according to the diet applied: control group (C): diet containing soybean oil as a source of fat; and saturated fatty acid group (S): diet containing butter as a source of fat. RESULTS: Histological and immunohistochemical analyses have been conducted. The immunohistochemical analyses of interleukin 6, suppressor of cytokine signaling, 3 and signal transducer and activator of transcription 3 did not demonstrate alterations in the expression of proteins in the fetuses of mothers fed with a saturated fatty diet. Moreover, no histopathological changes were noticed between groups. CONCLUSION: The saturated fatty diet does not induce tissue changes or activate the Janus kinase/signal transducer and activator of transcription signaling pathway during eye development in the fetuses of mothers with insulin resistance.

Developmental programming: An exploratory analysis of pancreatic islet compromise in female sheep resulting from gestational BPA exposure.

Developmental exposure to endocrine disruptors like bisphenol A (BPA) are implicated in later-life metabolic dysfunction. Leveraging a unique sheep model of developmental programming, we conducted an exploratory analysis of the programming effects of BPA on the endocrine pancreas. Pregnant ewes were administered environmentally relevant doses of BPA during gestational days (GD) 30-90, and pancreata from female fetuses and adult offspring were analyzed. Prenatal BPA exposure induced a trend toward decreased islet insulin staining and ß-cell count, increased glucagon staining and α-cell count, and increased α-cell/ß-cell ratio. Findings were most consistent in fetal pancreata assessed at GD90 and in adult offspring exposed to the lowest BPA dose. While not assessed in fetuses, adult islet fibrosis was increased. Collectively, these data provide further evidence that early-life BPA exposure is a likely threat to human metabolic health. Future studies should corroborate these findings and decipher the molecular mechanisms of BPA's developmental endocrine toxicity.

The role of curcumin during pregnancy on the exposed fetuses' tissues of Wistar rats to electromagnetic field.

To investigate curcumin (CUR) as the protector against the harmful effects of low-frequency electromagnetic field(LF- EMF, 50 Hz) during pregnancy period, 5 males and 15 females of Wistar rat mated and vaginal plaques were observed. Then, the pregnant rats were divided into six groups. During pregnancy(21 days), the EMF group was exposed to EMF for 30 min/day, the CUR group received a single dose of 50 mg/kg/daily CUR intraperitoneal, the EMF+CUR group was injected CUR and exposed to EMF daily. The DMSO(dimethyl sulfoxide) group was injected solvent of CUR (DMSO) intraperitoneal with the same volume of CUR solvent, the sham group was placed through the solenoid in the same conditions as the first group without exposure and the control group was kept in their cage in normal condition. After four weeks, babies born were divided according to the mother groups and sacrificed. Then, the three tissues injuries were investigated. EMF exposure led to an increase in outstanding necrotic areas in hippocampal tissue, an increase in the amount of hyperemia(p = 0.017) and necrotic(p = 0.005) in kidneys, and degeneration in liver tissue(p = 0.007) in the EMF group compared with EMF+CUR groups. A single dose of CUR daily during pregnancy can protect these tissues from injuries caused by LF-EMF exposure in rat fetuses.

Electromagnetic fields (EMFs) are able to penetrate and be absorbed by the body. The researchers showed that these radiations might be harmful and lead to cancers, cardiovascular diseases, mental disorders, and fetal abnormalities. Curcumin as an active component in turmeric has anti-inflammatory, antioxidant and anti-hyperlipidemia properties. It can protect the body against diseases such as arthritis, anxiety, and metabolic syndrome. This study examined the effects of curcumin as the protector against the harmful effects of EMF (50Hz) during pregnancy period. So the pregnant rats were divided into six groups. During pregnancy, a group was exposed to EMF for 30 min/day, the second group was injected a dose of curcumin 50mg/kg/daily, the third group was injected curcumin and exposed to EMF daily. The fourth group was injected a curcumin solvent dose, the sham group was placed through the field generator in the same conditions as the first group without exposure and the control group was kept in their cage in normal condition. After four weeks, babies born were divided according to the mother groups and sacrificed. Then, the liver, kidney, and hippocampal tissues were investigated. EMF exposure led to an outstanding increase in necrotic areas in hippocampal tissue, a notable increase in the amount of hyperemia and necrosis in kidneys, and degeneration in liver tissue(p=0.007) in the EMF group compared with the third group that was exposed to EMF and received curcumin. A single dose of curcumin daily during pregnancy can protect these tissues from injuries caused by EMF(50Hz) exposure in rat fetuses.

Single pulmonary nanopolystyrene exposure in late-stage pregnancy dysregulates maternal and fetal cardiovascular function.

Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. Previous work has demonstrated that xenobiotic pulmonary exposure to nanoparticles during gestation leads to maternal vascular impairments, as well as cardiovascular dysfunction within the fetus. Few studies have assessed the toxicological consequences of maternal nanoplastic (NP) exposure; therefore, the objective of this study was to assess maternal and fetal health after a single maternal pulmonary exposure to polystyrene NP in late gestation. We hypothesized that this acute exposure would impair maternal and fetal cardiovascular function. Pregnant rats were exposed to nanopolystyrene on gestational day 19 via intratracheal instillation. 24 h later, maternal and fetal health outcomes were evaluated. Cardiovascular function was assessed in dams using vascular myography ex vivo and in fetuses in vivo function was measured via ultrasound. Both fetal and placental weight were reduced after maternal exposure to nanopolystyrene. Increased heart weight and vascular dysfunction in the aorta were evident in exposed dams. Maternal exposure led to vascular dysfunction in the radial artery of the uterus, a resistance vessel that controls blood flow to the fetoplacental compartment. Function of the fetal heart, fetal aorta, and umbilical artery after gestational exposure was dysregulated. Taken together, these data suggest that exposure to NPs negatively impacts maternal and fetal health, highlighting the concern of MNPs exposure on pregnancy and fetal development.

Anesthetic recommendations for maternal and fetal safety in nonobstetric surgery: a balancing act.

PURPOSE OF REVIEW: Nonobstetric surgery during pregnancy is associated with maternal and fetal risks. Several physiologic changes create unique challenges for anesthesiologists. This review highlights physiologic changes of pregnancy and presents clinical recommendations based on recent literature to guide anesthetic management for the pregnant patient undergoing nonobstetric surgery. RECENT FINDINGS: Nearly every anesthetic technique has been safely used in pregnant patients. Although it is difficult to eliminate confounding factors, exposure to anesthetics could endanger fetal brain development. Perioperative fetal monitoring decisions require an obstetric consult based on anticipated maternal and fetal concerns. Given the limitations of fasting guidelines, bedside gastric ultrasound is useful in assessing aspiration risk in pregnant patients. Although there is concern about appropriateness of sugammadex for neuromuscular blockade reversal due its binding to progesterone, preliminary literature supports its safety. SUMMARY: These recommendations will equip anesthesiologists to provide safe care for the pregnant patient and fetus undergoing nonobstetric surgery.

α-Lipoic acid eliminates dioxin-induced offspring sexual immaturity by improving abnormalities in folic acid metabolism.

Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes developmental and reproductive disorders in pups due to the attenuated luteinizing hormone (LH) production during the perinatal stage; however, the administration of α-lipoic acid (LA) to TCDD-exposed pregnant rats reversed the attenuated LH production. Therefore, reproductive disorders in pups are expected to be ameliorated with LA supplementation. To address this issue, pregnant rats orally received low dose TCDD at gestational day 15 (GD15) and proceeded to parturition. The control received a corn oil vehicle. To examine the preventive effects of LA, supplementation with LA was provided until postnatal day 21. In this study, we demonstrated that maternal administration of LA restored the sexually dimorphic behavior of male and female offspring. TCDD-induced LA insufficiency is likely a direct cause of TCDD reproductive toxicity. In the analysis to clarify the mechanism of the decrease in LA, we found evidence suggesting that TCDD inhibits the synthesis and increases the utilization of S-adenosylmethionine (SAM), a cofactor for LA synthesis, resulting in a decrease in the SAM level. Furthermore, folate metabolism, which is involved in SAM synthesis, is disrupted by TCDD, which may adversely affect infant growth. Maternal supplementation of LA restored SAM to its original level in the fetal hypothalamus; in turn, SAM ameliorated abnormal folate consumption and suppressed aryl hydrocarbon receptor activation induced by TCDD. The study demonstrates that the application of LA could prevent and recover next-generation dioxin reproductive toxicity, which provides the potential to establish effective protective measures against dioxin toxicity.

Amelioration potential of Moringa oleifera extracts against sodium arsenate induced embryotoxicity and genotoxicity in mouse (Mus musculus) / Potencial de melhoria de extratos de Moringa oleifera contra embriotoxicidade e genotoxicidade induzida por arseniato de sódio em camundongos (Mus musculus)

Previous studies have suggested that arsenic crosses the placenta and affects the fetus development. The study under consideration aims to show comparative ameliorative effect of Moringa oleifera leaf and flower extracts against sodium arsenate induced fetus toxicity of mice. Pregnant mice (N=44) were kept in lab and divided into eleven group from (A to K) and were orally administered the doses 6 mg/kg, 12 mg/kg for sodium arsenate, 150 mg/kg and 300 mg/kg for Moringa oleifera leaf extracts (MOLE) and 150 mg/kg and 300 mg/kg for Moringa oleifera flower extracts (MOFE) comparing with control. The investigation revealed evident reduction in the fetuses weight, hind limb, fore limb, tail and snout length, crown rump and head circumferences well as malformations in tail, feet, arms, legs, skin and eyes in the negative control group (only administered with sodium arsenate). Co-administration of sodium arsenate with MOLE and MOFE ameliorate the reversed effect of sodium arsenate on the shape, length, body weight and DNA damage of fetus significantly at 95% confidence interval. However, Moringa oleifera leaf extract showed more significant results in comparison to Moringa oleifera flower extract. Hence concluded that Moringa oleifera leaf extract ameliorated the embryo toxic effects of sodium arsenate and can be used against environmental teratogens.

Estudos anteriores sugeriram que o arsênio atravessa a placenta e afeta o desenvolvimento do feto. O estudo em consideração visa mostrar o efeito melhorador comparativo de extratos de folhas e flores de Moringa oleifera contra a toxicidade fetal induzida por arseniato de sódio em camundongos. Camundongos grávidas (N = 44) foram mantidos em laboratório e divididos em 11 grupos (de A a K) e foram administrados por via oral nas doses de 6 mg/kg, 12 mg/kg para arseniato de sódio, 150 mg/kg e 300 mg/kg para extratos de folhas de Moringa oleifera (MOLE) e 150 mg/kg e 300 mg/kg para extratos de flores de Moringa oleifera (MOFE) em comparação com o controle. A investigação revelou redução evidente no peso do feto, membro posterior, membro anterior, comprimento da cauda e focinho, coroa, nádega e circunferência da cabeça, bem como malformações na cauda, pés, braços, pernas, pele e olhos no grupo de controle negativo (apenas administrado com arseniato de sódio). A coadministração de arseniato de sódio com MOLE e MOFE melhora significativamente o efeito reverso do arseniato de sódio na forma, comprimento, peso corporal e dano ao DNA do feto, com intervalo de confiança de 95%. No entanto, o extrato da folha da Moringa oleifera apresentou resultados mais significativos em comparação ao extrato da flor da Moringa oleifera. Portanto, concluiu que o extrato da folha de Moringa oleifera melhorou os efeitos tóxicos do arseniato de sódio para o embrião e pode ser usado contra teratógenos ambientais.

Current activities between the DevTox Berlin workshops and the Japanese Teratology Society Terminology Committee in harmonizing the terminology for classifying anomalies in laboratory animals in developmental toxicity studies: Report from the Satellite Workshop of the 60th Annual Meeting of the Japanese Teratology Society.

In recent years, the Japanese Teratology Society has worked with the DevTox Berlin Workshops project to provide internationally consistent terminology for teratogenic effects. This paper summarizes a satellite workshop of the 60th Annual Meeting of the Japanese Teratology Society, which was entitled "Current activities between DevTox Berlin Workshops to develop a harmonized terminology for classifying anomalies in laboratory animals in developmental toxicity studies." The Japanese Teratology Society - Laboratory Animal Terminology Project (JTS-LATP) reviewed "gray zone" anomalies and focused on developing criteria for reclassifying a large number of gray zone anomalies to clarify them and to make it easier to judge fetal categories. This effort will lead to international agreement, based on shared conceptions. The present article aimed to provide the reader with a summary of the issues discussed at the 2020 satellite meeting, which included discussions on open issues from the DevTox Berlin Workshops, ongoing work by the JTS-LATP on gray zone (GZ) anomalies, current industrial concerns, and future challenges.

Adult pancreatic islet endocrine cells emerge as fetal hormone-expressing cells.

The precise developmental dynamics of the pancreatic islet endocrine cell types, and their interrelation, are unknown. Some authors claim the persistence of islet cell differentiation from precursor cells after birth ("neogenesis"). Here, using four conditional cell lineage tracing ("pulse-and-chase") murine models, we describe the natural history of pancreatic islet cells, once they express a hormone gene, until late in life. Concerning the contribution of early-appearing embryonic hormone-expressing cells to the formation of islets, we report that adult islet cells emerge from embryonic hormone-expressing cells arising at different time points during development, without any evidence of postnatal neogenesis. We observe specific patterns of hormone gene activation and switching during islet morphogenesis, revealing that, within each cell type, cells have heterogeneous developmental trajectories. This likely applies to most maturating cells in the body, and explains the observed phenotypic variability within differentiated cell types. Such knowledge should help devising novel regenerative therapies.

Developmental toxicity studies on triclopyr acid, triclopyr butoxyethyl ester and triclopyr triethylamine salt in the rabbit.

Developmental toxicity studies have been conducted in the rabbit on triclopyr acid and its active-ingredient variants, triclopyr triethylamine salt (T-TEA) and triclopyr butoxyethyl ester (T-BEE), which are dissociated or hydrolysed in vivo to triclopyr acid. In this paper, the available developmental toxicity studies on triclopyr acid, T-TEA and T-BEE are summarised and evaluated. For triclopyr acid and T-TEA, there was no evidence of impaired reproductive performance, fetotoxicity, or teratogenicity, even at maternally toxic doses. The no-observed-adverse-effect levels (NOAELs) for developmental toxicity were 75 mg/kg bw per day for triclopyr acid and 100 mg/kg bw per day for T-TEA, equivalent to 72 mg/kg bw per day expressed as triclopyr acid. A study on T-BEE showed increased post-implantation loss and slight increases in skeletal anomalies and variants at the highest dose tested of 100 mg/kg bw per day, a maternally toxic dose. In a follow-up study on T-BEE, focusing on post-implantation loss, no general increase in post-implantation loss was observed, but one animal at 100 mg/kg bw per day with maternal toxicity had complete resorption of implants. The NOAEL for post-implantation loss was 60 mg/kg bw per day, equivalent to 44 mg/kg bw per day expressed as triclopyr acid. It cannot be excluded that T-BEE may be associated with increased post-implantation loss, but it was only seen in association with maternal toxicity. It is concluded that triclopyr acid and its variants are not specifically toxic to the rabbit embryo and fetus, since post-implantation loss only occurred at doses causing maternal toxicity.

Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5'-nucleotidase/CD73 in the Rat Fetal Brain.

Dexamethasone (DEX) is frequently used to treat women at risk of preterm delivery, but although indispensable for the completion of organ maturation in the fetus, antenatal DEX treatment may exert adverse sex-dimorphic neurodevelopmental effects. Literature findings implicated oxidative stress in adverse effects of DEX treatment. Purinergic signaling is involved in neurodevelopment and controlled by ectonucleotidases, among which in the brain the most abundant are ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) and ecto-5'-nucleotidase (e5'NT/CD73), which jointly dephosphorylate ATP to adenosine. They are also involved in cell adhesion and migration, processes integral to brain development. Upregulation of CD39 and CD73 after DEX treatment was reported in adult rat hippocampus. We investigated the effects of maternal DEX treatment on CD39 and CD73 expression and enzymatic activity in the rat fetal brain of both sexes, in the context of oxidative status of the brain tissue. Fetuses were obtained at embryonic day (ED) 21, from Wistar rat dams treated with 0.5 mg DEX/kg/day, at ED 16, 17, and 18, and brains were processed and used for further analysis. Sex-specific increase in CD39 and CD73 expression and in the corresponding enzyme activities was induced in the brain of antenatally DEX-treated fetuses, more prominently in males. The oxidative stress induction after antenatal DEX treatment was confirmed in both sexes, although showing a slight bias in males. Due to the involvement of purinergic system in crucial neurodevelopmental processes, future investigations are needed to determine the role of these observed changes in the adverse effects of antenatal DEX treatment.

Prenatal cyanuric acid exposure depresses hippocampal synaptic plasticity and induces spatial learning and memory deficits.

The infant and fetus may be exposed to cyanuric acid (CA) via several different routes into the diet or milk product as well as deliberate contamination. Previous findings indicated chronic CA treatment caused neurotransmission and synaptic impairment in the early developing hippocampus. This study was designed to characterize the effects of different doses (10 mg/kg, 20 mg/kg and 40 mg/kg) of CA exposure on the developing fetus. Pregnant rats were intraperitoneally exposed to CA during the entire period of gestation and male offspring were selected for water maze task, neural recording and N-methyl-d-aspartate (NMDA) receptor detection around the eighth postnatal week. We found that CA exposure impaired the learning and memory function in a dose-dependent manner. The paired-pulse ratio (PPR) and GluN2A-dependent long-term potentiation (LTP) at the Schaffer collateral-CA1 pathway were affected in CA-exposed rats. Remarkably, hippocampal levels of NMDA-GluN2A, but not NMDA-GluN2B, were significantly decreased. Meanwhile, the spine density of hippocampal CA1 neurons was not altered by the CA exposure. Our findings are consistent with the hypothesis that CA treatment during the prenatal period produces deficits in spatial cognition by disrupting hippocampal synaptic function.

COVID-19: can we treat the mother without harming her baby?

Medical care is predicated on 'do no harm', yet the urgency to find drugs and vaccines to treat or prevent COVID-19 has led to an extraordinary effort to develop and test new therapies. Whilst this is an essential cornerstone of a united global response to the COVID-19 pandemic, the absolute requirements for meticulous efficacy and safety data remain. This is especially pertinent to the needs of pregnant women; a group traditionally poorly represented in drug trials, yet a group at heightened risk of unintended adverse materno-fetal consequences due to the unique physiology of pregnancy and the life course implications of fetal or neonatal drug exposure. However, due to the complexities of drug trial participation when pregnant (be they vaccines or therapeutics for acute disease), many clinical drug trials will exclude them. Clinicians must determine the best course of drug treatment with a dearth of evidence from either clinical or preclinical studies, where at least in the short term they may be more focused on the outcome of the mother than of her offspring.

Duration of Exposure to General Endotracheal Anesthesia during Cesarean Deliveries at Term and Perinatal Complications.

OBJECTIVE: To examine whether the duration of time from initiation of general endotracheal anesthesia (GETA) to delivery for cesarean deliveries (CDs) performed is related to perinatal outcomes. STUDY DESIGN: This is a retrospective study of patients with singleton nonanomalous gestations undergoing CD ≥37 weeks of gestation under GETA with reassuring fetal status at a single tertiary care center from 2000 to 2016. Duration from GETA initiation until delivery was calculated as the time interval from GETA induction to delivery (I-D), categorized into tertiles. Outcomes for those in the tertile with the shortest I-D were compared with those in the other two tertiles. The primary perinatal outcome was a composite of complications (continuous positive airway pressure or high-flow nasal cannula for ≥2 consecutive hours, inspired oxygen ≥30% for ≥4 consecutive hours, mechanical ventilation, stillbirth, or neonatal death ≤72 hours after birth). Secondary outcomes were 5-minute Apgar score <7 and a composite of maternal morbidity (bladder injury, bowel injury, and extension of hysterotomy). Bivariable and multivariable analyses were used to compare outcomes. RESULTS: Two hundred eighteen maternal-perinatal dyads were analyzed. They were dichotomized based on I-D ≤4 minutes (those in the tertile with the shortest duration) or >4 minutes. Women with I-D >4 minutes were more likely to have prior abdominal surgery and less likely to have labored prior to CD. I-D >4 minutes was associated with significantly increased frequency of the primary perinatal outcome. This persisted after multivariable adjustment. In bivariable analysis, 5-minute Apgar <7 was more common in the group with I-D >4 minutes, but this did not persist in multivariable analysis. Frequency of maternal morbidity did not differ. CONCLUSION: When CD is performed at term using GETA without evidence of nonreassuring fetal status prior to delivery, I-D interval >4 minutes is associated with increased frequency of perinatal complications. KEY POINTS: · Cesarean delivery under general anesthesia is associated with increased perinatal complications.. · Perinatal complications are increased with increasing duration of exposure to general anesthetics.. · Maternal complications were not increased with shorter duration of exposure to general anesthesia..

Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial.

Pregnancy places a unique stress upon choline metabolism, requiring adaptations to support both maternal and fetal requirements. The impact of pregnancy and prenatal choline supplementation on choline and its metabolome in free-living, healthy adults is relatively uncharacterized. This study investigated the effect of prenatal choline supplementation on maternal and fetal biomarkers of choline metabolism among free-living pregnant persons consuming self-selected diets. Participants were randomized to supplemental choline (as choline chloride) intakes of 550 mg/d (500 mg/d d0-choline + 50 mg/d methyl-d9-choline; intervention) or 25 mg/d d9-choline (control) from gestational week (GW) 12-16 until Delivery. Fasting blood and 24-h urine samples were obtained at study Visit 1 (GW 12-16), Visit 2 (GW 20-24), and Visit 3 (GW 28-32). At Delivery, maternal and cord blood and placental tissue samples were collected. Participants randomized to 550 (vs. 25) mg supplemental choline/d achieved higher (p < .05) plasma concentrations of free choline, betaine, dimethylglycine, phosphatidylcholine (PC), and sphingomyelin at one or more study timepoint. Betaine was most responsive to prenatal choline supplementation with increases (p ≤ .001) in maternal plasma observed at Visit 2-Delivery (relative to Visit 1 and control), as well as in the placenta and cord plasma. Notably, greater plasma enrichments of d3-PC and LDL-C were observed in the intervention (vs. control) group, indicating enhanced PC synthesis through the de novo phosphatidylethanolamine N-methyltransferase pathway and lipid export. Overall, these data show that prenatal choline supplementation profoundly alters the choline metabolome, supporting pregnancy-related metabolic adaptations and revealing biomarkers for use in nutritional assessment and monitoring during pregnancy.

The exposure levels of phthalates in pregnant women and impact factors of fetal malformation.

METHODS: Urine samples were collected from 157 women with fetal malformations (case group) and 147 women with normal fetuses (control group). High-performance liquid chromatography-mass spectrometry (HPLC-MS) was used to detect the content of eight metabolites of phthalate compounds in urine, including monoethyl phthalate (MEP), mononbutyl phthalate (MBP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP). Demographic data were collected from questionnaires administered in specimen collection. RESULTS: The exposure level of MEOHP and MEHP in the case group was higher than the others. And there were significant differences between structural malformations and chromosomal malformations in the levels of MEHHP and MEOHP. Pregnant women with low income, high body mass index (BMI), frequent plastic contact, and low nutrients intake were at risk of suffering from fetal malformation. CONCLUSION: This study provides evidence for the correlation between the concentration of phthalates and fetal malformation. In addition, decreasing plastic exposure and supplementing nutrients may reduce the incidence of fetal malformations.

Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients.

Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR+ Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring's health.