Physiological adaptation in early human pregnancy: adaptation to balance maternal-fetal demands

After conception, the corpus luteum, placenta, and developing embryo release hormones, growth factors, and other substances into the maternal circulation. These substances trigger a cascade of events that transform the functioning of the maternal cardiovascular, respiratory, and renal systems, which in turn alter the physicochemical determinants of [H+]. Following implantation, maternal adaptations fulfill 4 important functions that support fetal growth. Increased availability of substrates and precursors for fetal-placental metabolism and hormone production is mediated by increases in dietary intake, as well as endocrine changes that increase the availability of glucose and low-density lipoprotein (LDL) cholesterol. Transport capacity is enhanced by increases in cardiac output, facilitating the transport of substrates and precursors to the placenta, and fetal waste products to maternal organs for disposal. Maternal-fetal exchange is regulated by the placenta after 10-12 weeks gestation, but it may occur through histiotrophic mechanisms before this time. Disposal of additional waste products (heat, carbon dioxide, and metabolic byproducts) occurs through peripheral vasodilation and increases in skin blood flow, ventilation, and renal filtration. The maternal physiological adaptations described above must meet the combined demands of maternal exercise and fetal growth. More research is needed to formulate evidence-based guidelines for healthy physical activity in early pregnancy.Key words: maternal adaptation, first trimester, exercise, fetal growth and development, hormones.

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First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study

Journal of Perinatal Medicine ◽

10.1515/jpm-2018-0120 ◽

2019 ◽

Vol 47 (2) ◽

pp. 161-168 ◽

Cited By ~ 6

Author(s):

Paula J. Correa ◽

Pia Venegas ◽

Yasna Palmeiro ◽

Daniela Albers ◽

Gregory Rice ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Case Control Study ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

First Trimester ◽

Case Control ◽

Low Density ◽

Control Study

AbstractObjectivesTo evaluate the first trimester maternal biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM).MethodsThe study was a case-control study of healthy women with singleton pregnancies at the first trimester carried out at the Obstetrics and Gynecology Unit, Clinica Davila, Santiago, Chile. After obtaining informed consent, peripheral blood samples of pregnant women under 14 weeks of gestation were collected. At 24–28 weeks of pregnancy, women were classified as GDM (n=16) or controls (n=80) based on the results of a 75-g oral glucose tolerance test (OGTT). In all women, we measured concentrations of fasting blood glucose, insulin, glycated hemoglobin, uric acid, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), sex hormone-binding globulin (SHBG), adiponectin, tissue plasminogen activator (t-PA), leptin and placental growth factor (PGF).ResultsThe GDM group displayed an increased median concentration of cholesterol (P=0.04), triglycerides (P=0.003), insulin (P=0.003), t-PA (P=0.0088) and homeostatic model assessment (HOMA) (P=0.003) and an increased mean concentration of LDL (P=0.009) when compared to the control group. The receiver operating characteristic (ROC) curve for significant variables achieved an area under the curve (AUC) of 0.870, a sensitivity of 81.4% and a specificity of 80.0%. The OGTT was positive for GDM according to the IADPSG (International Diabetes in Pregnancy Study Group) criteria.ConclusionWomen who subsequently developed GDM showed higher levels of blood-borne biomarkers during the first trimester, compared to women who did not develop GDM. These data warrant validation in a larger cohort.

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Haptoglobin Phenotype Modulates Lipoprotein-Associated Risk for Preeclampsia in Women With Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00723 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4743-4755

Author(s):

Clare B Kelly ◽

Jeremy Y Yu ◽

Alicia J Jenkins ◽

Alison J Nankervis ◽

Kristian F Hanssen ◽

...

Keyword(s):

Type 1 Diabetes ◽

Particle Concentration ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

First Trimester ◽

Cholesterol Ratio ◽

Multicenter Prospective Study ◽

Lipoprotein Profiles

Abstract Context The incidence of preeclampsia (PE) is increased in women with diabetes (∼20% vs ∼5% in the general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, the Hp 2-2 phenotype is associated with cardiorenal disease. Objective To investigate whether Hp phenotype is associated with PE in type 1 diabetes mellitus (T1DM) and/or modulates lipoprotein-associated risks. Design and Setting Multicenter prospective study of T1DM pregnancy. Patients Pregnant women with T1DM (normal albuminuria, normotensive at enrolment, n = 47) studied at three visits, all preceding PE onset: 12.3 ± 1.9, 21.8 ± 1.5, and 31.5 ± 1.6 weeks’ gestation (mean ± SD). Main Outcome Measures Hp phenotype and lipoprotein profiles in women with (n = 23) vs without (n = 24) subsequent PE. Results Hp phenotype did not predict PE, but lipoprotein associations with subsequent PE were confined to women with Hp 2-2, in whom the following associations with PE were observed: increased low-density lipoprotein (LDL) cholesterol, LDL particle concentration, apolipoprotein B (APOB), triacylglycerol/high-density lipoprotein (HDL) cholesterol ratio, and APOB/apolipoprotein AI (APOA1) ratio; decreased HDL cholesterol, APOA1, large HDL particle concentration, and peripheral lipoprotein lipolysis (all P < 0.05). In women with one or two Hp-1 alleles, no such associations were observed. Conclusions In women with T1DM, although Hp phenotype did not predict PE risk, lipoprotein-related risks for PE were limited to those with the Hp 2-2 phenotype. Hp phenotype may modulate PE risk in diabetes.

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Loss of Hepatic Surf4 Depletes Lipid Droplets in the Adrenal Cortex but Does Not Impair Adrenal Hormone Production

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.764024 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaole Chang ◽

Yongfang Zhao ◽

Shucun Qin ◽

Hao Wang ◽

Bingxiang Wang ◽

...

Keyword(s):

Adrenal Gland ◽

De Novo ◽

Cholesterol Biosynthesis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Hormone Production ◽

Adrenal Steroid ◽

Adult Mice ◽

Cholesterol Levels

The adrenal gland produces steroid hormones to play essential roles in regulating various physiological processes. Our previous studies showed that knockout of hepatic Surf4 (Surf4LKO) markedly reduced fasting plasma total cholesterol levels in adult mice, including low-density lipoprotein and high-density lipoprotein cholesterol. Here, we found that plasma cholesterol levels were also dramatically reduced in 4-week-old young mice and non-fasted adult mice. Circulating lipoprotein cholesterol is an important source of the substrate for the production of adrenal steroid hormones. Therefore, we investigated whether adrenal steroid hormone production was affected in Surf4LKO mice. We observed that lacking hepatic Surf4 essentially eliminated lipid droplets and significantly reduced cholesterol levels in the adrenal gland; however, plasma levels of aldosterone and corticosterone were comparable in Surf4LKO and the control mice under basal and stress conditions. Further analysis revealed that mRNA levels of genes encoding enzymes important for hormone synthesis were not altered, whereas the expression of scavenger receptor class B type I (SR-BI), low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methyl-glutaryl-CoA reductase was significantly increased in the adrenal gland of Surf4LKO mice, indicating increased de novo cholesterol biosynthesis and enhanced LDLR and SR-BI-mediated lipoprotein cholesterol uptake. We also observed that the nuclear form of SREBP2 was increased in the adrenal gland of Surf4LKO mice. Taken together, these findings indicate that the very low levels of circulating lipoprotein cholesterol in Surf4LKO mice cause a significant reduction in adrenal cholesterol levels but do not significantly affect adrenal steroid hormone production. Reduced adrenal cholesterol levels activate SREBP2 and thus increase the expression of genes involved in cholesterol biosynthesis, which increases de novo cholesterol synthesis to compensate for the loss of circulating lipoprotein-derived cholesterol in the adrenal gland of Surf4LKO mice.

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Evaluation of Oxidative Stress and some Biochemical Parameters in Normal Pregnant Women

ARO-The Scientific Journal of Koya University ◽

10.14500/aro.10541 ◽

2020 ◽

Vol 8 (1) ◽

pp. 17-23

Author(s):

Musher I. Kakey ◽

Kamaran K. Abdoulrahman ◽

Gulbahar R. Uthman

Keyword(s):

Pregnant Women ◽

Biochemical Parameters ◽

Hematological Parameters ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

First Trimester ◽

Control Group ◽

Sod Activity ◽

Nonsignificant Difference ◽

Group 2

Pregnancy is associated with many metabolic changes in normal pregnant woman, this leads to change in physiological, biochemical, and hematological parameters drastically. The test subjects were selected among those attending to Maternity Teaching Hospital in Erbil Governorate between March 2017 and August 2017. Four groups of individuals were included in this study, 230 pregnant women divided into three groups (Group 1 first trimester, Group 2 second trimester, and Group 3 third trimester) and Group 4 contained 90 nonpregnant women as control. Full automatic chemical analyzer (Cobas C311, Germany) was used to determine the biochemical parameters. The EL ×800 Absorbance Microplate Reader from BioTek (USA) instruments is used to measure the activity of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in serum. The results of this study showed a significant increase in serum albumin, glucose, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, urea, cholesterol, low-density lipoprotein, and MDA in pregnant women as compared to the control group, also show significant decrease in high-density lipoprotein (HDL) level, SOD activity, and CAT activity in pregnant women as compared to nonpregnant women, and nonsignificant difference in uric acid, and HDL.

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Increased Low-Density Lipoprotein Susceptibility to Oxidation in Pregnancies and Fetal Growth Restriction

Obstetrics and Gynecology ◽

10.1097/01.aog.0000171112.95083.86 ◽

2005 ◽

Vol 106 (2) ◽

pp. 345-351 ◽

Cited By ~ 14

Author(s):

Isabel Sánchez-Vera ◽

Bartolomé Bonet ◽

Marta Viana ◽

Amalia Quintanar ◽

Antonio López-Salva

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Growth Restriction ◽

Low Density

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Longitudinal Changes In Maternal Circulating Micrornas As Potential Biomarkers of Specific Events During Healthy Pregnancy

10.21203/rs.3.rs-928551/v2 ◽

2021 ◽

Author(s):

Erika Chavira-Suárez ◽

Alma Lilia Hernández-Olvera ◽

Mariana Flores-Torres ◽

Karen Rubí Celaya-Cruz ◽

Sofía Gitler ◽

...

Keyword(s):

Pregnant Women ◽

Fetal Growth ◽

Large Scale ◽

Late Pregnancy ◽

First Trimester ◽

Maternal Circulation ◽

Fetal Sex ◽

Circulating Micrornas ◽

Healthy Pregnancy ◽

Mirnas Expression

Abstract Background: Novel high-resolution tools for pregnancy monitoring, including early detection of prenatal disorders, are needed. Changes in circulating microRNAs (c-miRNAs) during pregnancy could potentially inform about the functional status of the mother, the placenta and/or the fetus. However, whether c-miRNA profiles actually reflect distinct pregnancy-specific events at all stages remains unclear.Methods: Longitudinal large-scale RNAseq c-miRNA profiles at early, middle and late pregnancy, and after birth derived from eight women with healthy term pregnancies (n=32 plasma samples) were compared against corresponding circulating profiles derived from age-matched non-pregnant women (n=10). Data of fetal sex and growth indicators obtained during pregnancy evolution of the same women, were used to identify specific c-miRNA correlates in circulation.Results: 1449 c-miRNAs were detected in circulation in both pregnant and non-pregnant women with only 48 c-miRNAs differentially expressed relative to non-pregnant controls in at least one of the four studied stages (FDR<0.05). Surprisingly, c-miRNA subpopulations with reported prominent expression in various pregnancy-associated compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found collectively under-expressed in maternal circulation throughout pregnancy (p<0.05). Furthermore, we found a bias in global miRNAs expression in direct association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth (R = 0.7, p < 0.01).Conclusion: Our results demonstrate the existence of temporal changes in c-miRNAs populations associated to distinct aspects of pregnancy, including correlates of placental function and lactation, as well as fetal gender and growth, revealing a wider potential of c-miRNAs as biomarkers of specific aspects of maternal health and fetal growth.

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Materno-fetal cholesterol transport during pregnancy

Biochemical Society Transactions ◽

10.1042/bst20190129 ◽

2020 ◽

Vol 48 (3) ◽

pp. 775-786 ◽

Cited By ~ 2

Author(s):

Sampada Kallol ◽

Christiane Albrecht

Keyword(s):

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Cholesterol Transport ◽

Low Density ◽

Maternal Circulation ◽

Fetal Circulation ◽

Apical Side ◽

Class 1

Cholesterol is a major nutrient required for fetal growth. It is also a precursor for the synthesis of steroid hormones and essential for the development and maturation of fetal organs. During pregnancy, the placenta controls the transport of cholesterol from the mother to the fetus and vice versa. Cholesterol originating from the maternal circulation has to cross two main membrane barriers to reach the fetal circulation: Firstly, cholesterol is acquired by the apical side of the syncytiotrophoblast (STB) from the maternal circulation as high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)- or very-low-density lipoprotein (VLDL)-cholesterol and secreted at the basal side facing the villous stroma. Secondly, from the villous stroma cholesterol is taken up by the endothelium of the fetal vasculature and transported to the fetal vessels. The proteins involved in the uptake of HDL-, LDL-, VLDL- or unesterified-cholesterol are scavenger receptor type B class 1 (SR-B1), cubulin, megalin, LDL receptor (LDLR) or Niemann–Pick-C1 (NPC1) which are localized at the apical and/or basal side of the STB or at the fetal endothelium. Through interaction with apolipoproteins (e.g. apoA1) cholesterol is effluxed either to the maternal or fetal circulation via the ATP-binding-cassette (ABC)-transporter A1 and ABCG1 localized at the apical/basal side of the STB or the endothelium. In this mini-review, we summarize the transport mechanisms of cholesterol across the human placenta, the expression and localization of proteins involved in the uptake and efflux of cholesterol, and the expression pattern of cholesterol transport proteins in pregnancy pathologies such as pre-eclampsia, gestational diabetes mellitus and intrauterine growth retardation.

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The importance of iodine nutrition during pregnancy

Public Health Nutrition ◽

10.1017/s1368980007360886 ◽

2007 ◽

Vol 10 (12A) ◽

pp. 1542-1546 ◽

Cited By ~ 129

Author(s):

Daniel Glinoer

Keyword(s):

Pregnant Women ◽

Breast Feeding ◽

Salt Intake ◽

First Trimester ◽

Physiological Adaptation ◽

Hormone Production ◽

Iodine Nutrition ◽

Iodised Salt ◽

Proportional Increase ◽

Health Programmes

AbstractObjective:To examine the importance of iodine nutrition during pregnancy.Design:Review of existing literature of iodine in pregnancy.Setting:Population surveys and metabolic studies.Subjects:Pregnant women.Results:The main changes in thyroid function associated with pregnancy are due to an increase in hormone requirements that begin in the first trimester of gestation. This increase can only be met by a proportional increase in hormone production, something that depends directly upon the availability of iodine. When dietary iodine is lacking, an adequate physiological adaptation is difficult to achieve and is progressively replaced by pathological alterations that occur in parallel with the degree and duration of iodine deprivation.Conclusions:Iodine prophylaxis should be given systematically to women during pregnancy. In most public health programmes dealing with the correction of iodine deficiency disorders, iodised salt has been used as the preferred means to deliver iodine to households. Iodised salt, however, is not the ideal means of delivering iodine in the specific instances of pregnancy, breast-feeding and complementary feeding because of the need to limit salt intake during these periods. In European countries, presently it is proposed that iodine is given to pregnant women and breast-feeding mothers by systematically administering multivitamin tablets containing iodine in order to reach the recommended dietary allowance of 250 μg iodine day-1.

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Metabolic and oxidative status of West African dwarf does at different reproductive stages in southwest Nigeria

Bulletin of the National Research Centre ◽

10.1186/s42269-019-0223-6 ◽

2019 ◽

Vol 43 (1) ◽

Author(s):

Abubakar Olatunji Jimoh ◽

Olayinka Abosede Ojo ◽

Uchechi Daureen Gift Ihejirika

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Antioxidant Activity ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

First Trimester ◽

West African ◽

Late Gestation ◽

West African Dwarf ◽

Serum Biochemical

Abstract Background A study was conducted to investigate changes in oxidative stress indicators of West African dwarf (WAD) goats at different reproductive stages. There are a total of 35 dry does, 30 gravid does at first trimester (40–45 days post-mating), 33 gravid does at second trimester (85–90 days post-mating), 31 gravid does at third trimester (135–140 days post-mating), and 40 postpartum does (30–35 days postpartum). Fastened blood samples were collected from all tagged animals and serum obtained. Serum was assayed for lipid peroxidation, total antioxidant activity, glutathione peroxidase, catalase and superoxide dismutase, serum biochemical, glucose, total protein, albumin, cholesterol, triglyceride, high-density lipoprotein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine using standard procedures. Results Result revealed that intense metabolic changes were associated with late prepartum and postpartum does as pronounced in oxidative and biochemical indicators of WAD does. Significant differences were found in serum biochemical indices across the different physiological stages of the doe except for triglyceride and low-density lipoprotein. Antioxidant defense is higher at early and mid-gestation and dry does, through low lipid peroxidation and high antioxidant activity as compared to late gestation and lactation does. Conclusion The observed result shows that the WAD does display oxidative stress during late gestation and lactation owing to intense metabolism. Antioxidant fortification should be employed especially during late gestation and lactation to counteract the oxidative stress in WAD goats.

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Longitudinal changes in maternal circulating microRNAs as potential biomarkers of specific events during healthy pregnancy

10.21203/rs.3.rs-928551/v1 ◽

2021 ◽

Author(s):

Erika Chavira-Suárez ◽

Alma Lilia Hernández-Olvera ◽

Mariana Flores-Torres ◽

Karen Rubí Celaya-Cruz ◽

Sofía Gitler ◽

...

Keyword(s):

Pregnant Women ◽

Fetal Growth ◽

Large Scale ◽

Late Pregnancy ◽

First Trimester ◽

Maternal Circulation ◽

Fetal Sex ◽

Circulating Micrornas ◽

Healthy Pregnancy ◽

Mirnas Expression

Abstract BackgroundNovel high-resolution tools for pregnancy monitoring, including early detection of prenatal disorders, are needed. Changes in circulating microRNAs (c-miRNAs) during pregnancy could potentially inform about the functional status of the mother, the placenta and/or the fetus. However, whether c-miRNA profiles actually reflect distinct pregnancy-specific events at all stages remains unclear.MethodsLongitudinal large-scale RNAseq c-miRNA profiles at early, middle and late pregnancy, and after birth derived from eight women with healthy term pregnancies (n = 32 plasma samples) were compared against corresponding circulating profiles derived from age-matched non-pregnant women (n = 10). Data of fetal sex and growth indicators obtained during pregnancy evolution of the same women, were used to identify specific c-miRNA correlates in circulation.Results1449 c-miRNAs were detected in circulation in both pregnant and non-pregnant women with only 48 c-miRNAs differentially expressed relative to non-pregnant controls in at least one of the four studied stages (FDR < 0.05). Surprisingly, c-miRNA subpopulations with reported prominent expression in various pregnancy-associated compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found collectively under-expressed in maternal circulation throughout pregnancy (p < 0.05). Furthermore, we found a bias in global miRNAs expression in direct association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth (R = 0.7, p < 0.01).ConclusionOur results demonstrate the existence of temporal changes in c-miRNAs populations associated to distinct aspects of pregnancy, including correlates of placental function and lactation, as well as fetal gender and growth, revealing a wider potential of c-miRNAs as biomarkers of specific aspects of maternal health and fetal growth.

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