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1.
Maternal cholesterol levels during gestation: boon or bane for the offspring?
Jayalekshmi, VS, Ramachandran, S
Molecular and cellular biochemistry. 2021;(1):401-416
Abstract
An increase in cholesterol levels is perceived during pregnancy and is considered as a normal adaptive response to the development of the fetus. In some pregnancies, excessive increase in total cholesterol with high levels of Low-Density Lipoprotein leads to maladaptation by the fetus to cholesterol demands, resulting in a pathological condition termed as maternal hypercholesterolemia (MH). MH is considered clinically irrelevant and therefore cholesterol levels are not routinely checked during pregnancy, as a consequence of which there is scarce information on its global prevalence in pregnant women. Studies have reported that MH during pregnancy can cause atherogenesis in adults emphasizing the concept of in utero programming of fetus. Moreover, Gestational Diabetes Mellitus, obesity and Polycystic Ovary Syndrome are potential risk factors which strengthen combined pathologies in placenta and fetuses of mothers with MH. However, lack of conclusive evidence on cholesterol transport and underlying programming demand substantial research to develop population-based life style strategies for women in their childbearing years. The current review focuses on the mechanisms and outcomes of MH from existing epidemiological as well as experimental data and presents a detailed insight on this novel risk factor of cardiovascular diseases.
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2.
Changes in fatty acid levels (saturated, monounsaturated and polyunsaturated) during pregnancy.
Aparicio, E, Martín-Grau, C, Hernández-Martinez, C, Voltas, N, Canals, J, Arija, V
BMC pregnancy and childbirth. 2021;(1):778
Abstract
BACKGROUND During pregnancy a high amount of fatty acids (FA) is necessary to meet foetus demands, which vary during gestation. The present study describes the changes in maternal fatty acid concentrations during pregnancy in a sample of pregnant women. METHODS This is a longitudinal study of 479 pregnant women who were monitored from the first trimester to third trimester of pregnancy. Data on maternal characteristics were recorded and a serum sample was collected in each trimester. The fatty acid profile (saturated (SFA: total, lauric acid, myristic acid, palmitic acid, stearic acid), monounsaturated (MUFA: total, palmitoleic acid, oleic acid) and polyunsaturated fatty acids (PUFA: total omega-6 (n-6), linoleic acid, dihomo-γ-linolenic acid, arachidonic acid (AA), total omega-3 (n-3), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) was analysed with a gas chromatography-mass spectrometry combination. RESULTS From the first trimester to third trimester of pregnancy, a significant increase in total SFA, total MUFA and total n-6 PUFA was found. (p < 0.001). Nevertheless, the serum concentration of arachidonic acid (AA), eicosapentaenoic acid (EPA) and total n-3 PUFA decreased during gestation (p < 0.001). A statistically non-significant result was observed for the docosahexaenoic acid (DHA) serum concentration between the first and third trimesters of pregnancy. Significant correlations were observed between each total fatty acid concentrations of the first and third trimesters. CONCLUSION The circulating serum concentration of SFA, MUFA and n-6 PUFA increases during pregnancy, whereas essential fatty acids such as AA and EPA decrease, and DHA remains unchanged. Further research is necessary to understand the role played by FA throughout gestation.
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3.
One-carbon metabolism during the menstrual cycle and pregnancy.
Kim, R, Nijhout, HF, Reed, MC
PLoS computational biology. 2021;(12):e1009708
Abstract
Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B12, vitamin B6, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.
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4.
Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells.
Thomas, JR, Appios, A, Zhao, X, Dutkiewicz, R, Donde, M, Lee, CYC, Naidu, P, Lee, C, Cerveira, J, Liu, B, et al
The Journal of experimental medicine. 2021;(1)
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Abstract
Hofbauer cells (HBCs) are a population of macrophages found in high abundance within the stroma of the first-trimester human placenta. HBCs are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive hematopoiesis, we find that HBCs are transcriptionally similar to yolk sac macrophages. Phenotypically, HBCs can be identified as HLA-DR-FOLR2+ macrophages. We identify a number of factors that HBCs secrete (including OPN and MMP-9) that could affect placental angiogenesis and remodeling. We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.
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Toward a more stable understanding of pregnancy micronutrient metabolism.
Klatt, KC, Smith, ER, Barberio, MD
American journal of physiology. Endocrinology and metabolism. 2021;(2):E260-E263
Abstract
There is an urgent need to better understand the micronutrient demands of pregnancy due to the complex physiological adaptations during the gestational period and the importance of micronutrients in maternal-fetal health. Rigorous studies of micronutrients in pregnancy are significantly lacking due to a number of issues including the exclusion of pregnant people in research, methodological barriers to studying micronutrients, and the multidisciplinary expertise required for such studies. Stable isotopes present a unique methodological opportunity to quantify pregnancy-related changes in the absorption, distribution, metabolism, and excretion of micronutrients. We demonstrate here through a rapid review of the published literature that this approach is dramatically underutilized outside of calcium. In this perspective, we discuss the use of stable isotopes to study micronutrient physiology and our experiences in addressing the need for more studies in this area. Finally, we discuss how we might overcome major barriers to move toward a better understanding of micronutrient physiology in pregnancy.
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Nutritional Iodine Status in Pregnant Women from Health Area IV in Asturias (Spain): Iodised Salt Is Enough.
González-Martínez, S, Riestra-Fernández, M, Martínez-Morillo, E, Avello-Llano, N, Delgado-Álvarez, E, Menéndez-Torre, EL
Nutrients. 2021;(6)
Abstract
BACKGROUND Iodine deficiency during pregnancy may have adverse effects on the neurodevelopment of the foetus. Recent studies of pregnant women in Asturias (Spain) indicate that nutritional iodine levels are sufficient. The objective of this study was to confirm the appropriate nutritional iodine status and to analyse the influence of the ingestion of iodine on maternal urinary iodine concentration (UIC) and thyroid function. METHODS An observational study was carried out between May and June 2017 on women in the first trimester of pregnancy from Health Area IV in Asturias. The women completed a questionnaire related to their consumption of iodine and samples were taken to analyse UIC and thyroid function. RESULTS Three hundred and eighteen pregnant women were involved. Of these, 51.10% used iodised salt, 48.90% consumed ≥ 2 servings of dairy products daily and 87.08% took iodine supplements. The median UIC was 171.5 μg/L (116-265 μg/L) and 60.41% of women had UIC ≥ 150 μg/L. Multivariate logistic regression analysis demonstrated that iodised salt had a protective effect on UIC < 150 μg/L (odds ratio (OR) 0.404 (0.237-0.683), p = 0.001), but not iodine supplements (OR 0.512 (0.240-1.085), p = 0.080). The average level of thyroid stimulating hormone (TSH) was 2.26 ± 0.94 mIU/L; 68.40% of pregnant women taking iodine supplements had TSH < 2.5 mIU/L compared to 30.00% of those who were not taking supplements (p = 0.031). CONCLUSIONS The pregnant women in our health area are maintaining appropriate nutritional iodine levels. The consumption of iodised salt protects against iodine deficiency; thus, iodine supplements should be taken on an individualised basis.
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Extracellular vesicles and their potential role inducing changes in maternal insulin sensitivity during gestational diabetes mellitus.
Nair, S, Ormazabal, V, Lappas, M, McIntyre, HD, Salomon, C
American journal of reproductive immunology (New York, N.Y. : 1989). 2021;(2):e13361
Abstract
Gestational diabetes mellitus (GDM) is one of the most common endocrine disorders during gestation and affects around 15% of all pregnancies worldwide, paralleling the global increase in obesity and type 2 diabetes. Normal pregnancies are critically dependent on the development of maternal insulin resistance balanced by an increased capacity to secrete insulin, which allows for the allocation of nutrients for adequate foetal growth and development. Several factors including placental hormones, inflammatory mediators and nutrients have been proposed to alter insulin sensitivity and insulin response and underpin the pathological outcomes of GDM. However, other factors may also be involved in the regulation of maternal metabolism and a complete understanding of GDM pathophysiology requires the identification of these factors, and the mechanisms associated with them. Recent studies highlight the potential utility of tissue-specific extracellular vesicles (EVs) in the diagnosis of disease onset and treatment monitoring for several pregnancy-related complications, including GDM. To date, there is a paucity of data defining changes in the release, content, bioactivity and diagnostic utility of circulating EVs in pregnancies complicated by GDM. Placental EVs may engage in paracellular interactions including local cell-to-cell communication between the cell constituents of the placenta and contiguous maternal tissues, and/or distal interactions involving the release of placental EVs into biological fluids and their transport to a remote site of action. Hence, the aim of this review is to discuss the biogenesis, isolation methods and role of EVs in the physiopathology of GDM, including changes in maternal insulin sensitivity during pregnancy.
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Do maternal urinary iodine concentration or thyroid hormones within the normal range during pregnancy affect growth parameters at birth? A systematic review and meta-analysis.
Nazeri, P, Shab-Bidar, S, Pearce, EN, Shariat, M
Nutrition reviews. 2020;(9):747-763
Abstract
CONTEXT Iodine, an essential constituent of thyroid hormones, is required for proper growth and development. OBJECTIVE To investigate whether growth parameters at birth are associated with maternal urinary iodine concentration (UIC) or normal ranges of thyroid hormones during pregnancy. DATA SOURCES Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, electronic databases (namely, MEDLINE, Web of Science, the Cochrane Library, Scopus, and Google Scholar) were searched between January 1988 and November 2018 to identify relevant articles. DATA EXTRACTION Data from the studies included were independently extracted by 2 investigators using standardized forms developed for this review. DATA ANALYSIS The pooled mean birth weight, length, and head circumference values, and 95% confidence intervals were estimated in newborns born to women with UIC < 150 and UIC ≥150 μg/L during pregnancy. Possible linear or nonlinear associations between maternal UIC and the aforementioned anthropometric measures were evaluated. A narrative synthesis of the data was performed for thyroid hormones with levels within the normal range. RESULTS Of the 123 studies identified, 11 were eligible for inclusion in the meta-analysis. The pooled mean birth weight, length, and head circumference in newborns whose mothers had UIC < 150 μg/L vs UIC ≥150 μg/L were 2898 g vs 2900 g (P = 0.970), 49.6 cm vs 49.4 cm (P = 0.880), and 34.0 cm vs 34.1 cm (P = 0.933), respectively. Dose-response meta-analyses revealed no significant linear or nonlinear associations between maternal UIC during pregnancy and anthropometric measures at birth. Among the different thyroid function parameters evaluated, high-normal values of maternal free thyroxine and thyrotropin during pregnancy were inversely associated with neonatal birth weight. CONCLUSION This systematic review showed that birth weight may be affected by even mild variations in the normal concentrations of maternal thyroid hormones. However, in the current meta-analysis, birth anthropometric measures were not associated with maternal UIC during pregnancy.
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In pregnancy, maternal HDL is specifically enriched in, and carries the highest proportion of, DHA in plasma.
Zamai, N, Cortie, CH, Jarvie, EM, Onyiaodike, CC, Alrehaili, A, Francois, M, Freeman, DJ, Meyer, BJ
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102209
Abstract
Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important for neurological development. The aim was to determine the distribution and relative enrichment of AA and DHA among lipoprotein fractions prior to pregnancy, throughout gestation and in the post-partum period. Our hypothesis was that in pregnancy, in contrast to the non-pregnant state, AA and DHA are carried in highest concentration in the very low density lipoprotein (VLDL) fraction secondary to increased gestational liver triglyceride secretion. Two independent prospective, observational cohort studies carried out in Glasgow were combined; one early in pregnancy and one later in pregnancy with post-partum follow up. Across the pregnancy timeline plasma lipoproteins were isolated using sequential ultracentrifugation and lipoprotein fatty acids were extracted and analysed by gas chromatography. High density lipoprotein (HDL) had the highest concentration of AA and DHA compared to other lipoproteins. HDL became progressively enriched in the proportion of triglycerides at 16 weeks of gestation, which peaked at 35 weeks and returned to baseline at 13 weeks postpartum. HDL DHA per HDL-cholesterol and HDL DHA per apoA-I became progressively enriched at 16 weeks of gestation, peaked at 25 weeks and returned to baseline at 13 weeks postpartum, whereas HDL AA (per HDL-C or HDL-apoA-I) did not differ. DHA is carried primarily in HDL rather than VLDL. HDL has anti-oxidant properties that might afford DHA protection against oxidation.
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10.
Anatomy and Physiology of the Breast during Pregnancy and Lactation.
Alex, A, Bhandary, E, McGuire, KP
Advances in experimental medicine and biology. 2020;:3-7
Abstract
The mature breast is located within the anterior thoracic wall, lying atop the pectoralis major muscle. Pubertal changes lead to incomplete development of the breast , a process which is only completed during pregnancy . The incomplete breast consists mostly of adipose tissue but also lactiferous units called lobes. These eventually drain into the lactiferous ducts and then into the lactiferous sinus and then to the nipple-areolar complex. During pregnancy , the breast undergoes both anatomic and physiologic changes to prepare for lactation. During the first trimester, the ductal system expands and branches out into the adipose tissue in response to the increase of estrogen. Elevated levels of estrogen also cause a decrease in adipose tissue and ductal proliferation and elongation. Estrogen also stimulates the pituitary gland which leads to elevated levels of prolactin. By the twentieth week of gestation, mammary glands are sufficiently developed to produce components of milk due to prolactin stimulation. Milk production is inhibited by high estrogen and progesterone levels and colostrum is produced during this time. In the third trimester and then rapidly after birth, these levels decrease, allowing for milk production and eventual let-down to allow for breastfeeding. Most pregnancies cause the areola to darken, the breast to increase in size, and the Montgomery glands to become more prominent. Post-lactational involution occurs at the cessation of milk production caused by a decline in prolactin.