Maternal hypothyroidism in rats reduces placental lactogen, lowers insulin levels and causes glucose intolerance

Endocrinology ◽  
2021 ◽  
Author(s):  
Nykola Louise Kent ◽  
Sharat Chandra Atluri ◽  
James Sebastian Martin Cuffe
Keyword(s):  
Beta Cell ◽  
Glucose Intolerance ◽  
Insulin Signalling ◽  
Placental Lactogen ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Cross Sectional ◽  
Altered Expression ◽  
Expression Of Genes ◽  
In Pregnancy

Abstract Hypothyroidism increases incidence of gestational diabetes mellitus (GDM) but the mechanisms responsible are unknown. This study aimed to assess the pathophysiological mechanisms by which hypothyroidism leads to glucose intolerance in pregnancy. Hypothyroidism was induced in female Sprague-Dawley rats by adding methimazole (MMI) to drinking water at moderate (MOD, MMI at 0.005% w/v) and severe (SEV, MMI at 0.02% w/v) doses from one week prior to pregnancy and throughout gestation. A non-pregnant cohort received the same dose for the same duration but were not mated. On gestational day 16 (GD16), or non-pregnant day 16 (NP16), animals were subjected to an intraperitoneal glucose tolerance test. Tissues and blood samples were collected four days later. Hypothyroidism induced a diabetic-like phenotype by GD16 in pregnant females only. Pregnant MOD and SEV females had reduced fasting plasma insulin, less insulin following a glucose load and altered expression of genes involved in insulin signalling within skeletal muscle and adipose tissue. Hypothyroidism reduced rat placental lactogen concentrations, which was accompanied by reduced percentage beta-cell cross-sectional area (CSA) relative to total pancreas CSA, and a reduced number of large beta cell clusters in the SEV hypothyroid group. Plasma triglycerides and free fatty acids were reduced due to hypothyroidism in pregnant rats, as was the expression of genes that regulate lipid homeostasis. Hypothyroidism in pregnant rats results in a diabetic-like phenotype that is likely mediated by impaired beta cell expansion in pregnancy. This pregnancy specific phenomenon is likely due to reduced placental lactogen secretion.

Accretion of visceral fat and hepatic insulin resistance in pregnant rats

2008 ◽  
Vol 294 (2) ◽  
pp. E451-E455 ◽  
Author(s):  
Francine H. Einstein ◽  
Sigal Fishman ◽  
Radhika H. Muzumdar ◽  
Xiao Man Yang ◽  
Gil Atzmon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Visceral Fat ◽  
Hepatic Glucose Production ◽  
Late Gestation ◽  
Hepatic Insulin Resistance ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Hepatic Insulin Sensitivity ◽  
In Pregnancy

Insulin resistance (IR) is a hallmark of pregnancy. Because increased visceral fat (VF) is associated with IR in nonpregnant states, we reasoned that fat accretion might be important in the development of IR during pregnancy. To determine whether VF depots increase in pregnancy and whether VF contributes to IR, we studied three groups of 6-mo-old female Sprague-Dawley rats: 1) nonpregnant sham-operated rats (Nonpreg; n = 6), 2) pregnant sham-operated rats (Preg; n = 6), and 3) pregnant rats in which VF was surgically removed 1 mo before mating (PVF−; n = 6). VF doubled by day 19 of pregnancy (Nonpreg 5.1 ± 0.3, Preg 10.0 ± 1.0 g, P < 0.01), and PVF− had similar amounts of VF compared with Nonpreg (PVF− 4.6 ± 0.8 g). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp in late gestation in chronically catheterized unstressed rats. Glucose IR (mg·kg−1·min−1) was highest in Nonpreg (19.4 ± 2.0), lowest in Preg (11.1 ± 1.4), and intermediate in PVF− (14.7 ± 0.6; P < 0.001 between all groups). During the clamp, Nonpreg had greater hepatic insulin sensitivity than Preg [hepatic glucose production (HGP): Nonpreg 4.5 ± 1.3, Preg 9.3 ± 0.5 mg·kg−1·min−1; P < 0.001]. With decreased VF, hepatic insulin sensitivity was similar to nonpregnant levels in PVF− (HGP 4.9 ± 0.8 mg·kg−1·min−1). Both pregnant groups had lower peripheral glucose uptake compared with Nonpreg. In parallel with hepatic insulin sensitivity, hepatic triglyceride content was increased in pregnancy (Nonpreg 1.9 ± 0.4 vs. Preg 3.2 ± 0.3 mg/g) and decreased with removal of VF (PVF− 1.3 ± 0.4 mg/g; P < 0.05). Accretion of visceral fat is an important component in the development of hepatic IR in pregnancy, and accumulation of hepatic triglycerides is a mechanism by which visceral fat may modulate insulin action in pregnancy.

Effect of bromocryptine on 20α-hydroxysteroiddehydrogenase regulation in the corpus luteum of the pregnant rat

1981 ◽  
Vol 98 (1) ◽  
pp. 133-136 ◽  
Author(s):  
K. Loewit ◽  
R. Kofler ◽  
M. Tabarelli ◽  
S. Schwarz
Keyword(s):  
Enzyme Activity ◽  
Luteinizing Hormone ◽  
Corpus Luteum ◽  
Placental Lactogen ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Sprague Dawley Rats ◽  
Effective Doses

Abstract. Pregnant Sprague Dawley rats were passively immunized with antiserum to bovine luteinizing hormone (anti-LH) on day 10 of pregnancy, and treated with 1 mg/day or 1.5 mg/day of the prolactin (Prl) inhibitor bromocryptine (BEC) between days 10 to 12 or 9 to 12, respectively. On day 12 a laparotomy was performed to assess the state of pregnancy and to remove the ovaries for histochemical detection of 20α-hydroxysteroiddehydrogenase (20α-OHSD) in the corpora lutea of pregnancy. In a second experiment pregnant rats were treated with 1.5mg BEC/day from days 17 to 22, checked for foetal state and ovariectomized on day 22 before giving birth. Treatment with BEC in effective doses did not interfere with anti-LH-induced termination of pregnancy and consequent reappearance of 20α-OHSD activity on day 12, or with spontanenous recurrence of enzyme activity at the end of gestation. It is concluded that Prl has no direct and immediate role in 20α-OHSD regulation, at least on day 12, although substitution by endogenous rat placental lactogen at the end of pregnancy cannot be excluded.

scholarly journals Maternal sitagliptin treatment attenuates offspring glucose metabolism and intestinal proinflammatory cytokines IL-6 and TNF-α expression in male rats

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10310
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Intolerance ◽  
Normal Diet ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Tnf Α ◽  
Pregnancy And Lactation ◽  
Maternal Overnutrition

Increasing evidence shows that maternal overnutrition may increase the risk of diabetes in offspring. We hypothesized that maternal sitagliptin intervention may improve glucose intolerance through gut targeting. Female Sprague-Dawley (SD) rats were fed a normal diet (ND) or a high-fat diet (HFD) for 4 weeks before mating. ND pregnant rats were divided into two subgroups: ND group (ND alone) and the ND-sitagliptin group (ND combined with 10 mg/kg/day sitagliptin treatment). HFD pregnant rats were randomized to one of two groups: HFD group (HFD alone) and the HFD-sitagliptin group (HFD combined with 10 mg/kg/day sitagliptin treatment) during pregnancy and lactation. Glucose metabolism was assessed in offspring at weaning. Intestinal gene expression levels were investigated. Maternal sitagliptin intervention moderated glucose intolerance and insulin resistance in male pups. Moreover, maternal sitagliptin treatment inhibited offspring disordered intestinal expression of proinflammatory markers, including interleukin-6 (Il6), ll1b, and tumor necrosis factor (Tnf), at weaning and reduced intestinal IL-6, TNF-α expression by immunohistochemical staining and serum IL-6, TNF-α levels. However, maternal sitagliptin intervention did not affect offspring serum anti-inflammatory cytokine IL-10 level. Our results are the first to show that maternal sitagliptin intervention moderated glucose metabolism in male offspring. It may be involved with moderating intestinal IL-6 and TNF-α expression in male rat offspring.

Quantifying Pregnant Women’s Knowledge of Educational Components of Antenatal Care in Lesotho

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Tabeta Seeiso ◽  
Mamutle M. Todd-Maja
Keyword(s):  
Antenatal Care ◽  
Maternal Mortality ◽  
Pregnant Women ◽  
Rural Areas ◽  
Geographic Location ◽  
Sub Saharan Africa ◽  
World Health ◽  
Cross Sectional ◽  
Danger Signs ◽  
In Pregnancy

Antenatal care (ANC) literacy is particularly important for pregnant women who need to make appropriate decisions for care during their pregnancy and childbirth. The link between inadequate health literacy on the educational components of ANC and maternal mortality in sub-Saharan Africa (SSA) is undisputable. Yet, little is known about the ANC literacy of pregnant women in SSA, with most studies inadequately assessing the four critical components of ANC literacy recommended by the World Health Organization, namely danger signs in pregnancy; true signs of labour; nutrition; and preparedness for childbirth. Lesotho, a country with one of the highest maternal mortality rates in SSA, is also underexplored in this research area. This cross-sectional study explored the levels of ANC literacy and the associated factors in 451 purposively sampled women in two districts in Lesotho using a structured questionnaire, making recourse to statistical principles. Overall, 16.4 per cent of the participants had grossly inadequate ANC literacy, while 79.8 per cent had marginal levels of such knowledge. The geographic location and level of education were the most significant predictors of ANC literacy, with the latter variable further subjected to post hoc margins test with the Bonferroni correction. The participants had the lowest scores on knowledge of danger signs in pregnancy and true signs of labour. Adequate ANC literacy is critical to reducing maternal mortality in Lesotho. Improving access to ANC education, particularly in rural areas, is recommended. This study also provides important recommendations critical to informing the national midwifery curriculum.

scholarly journals Characterization of Differentially Expressed Circulating miRNAs in Metabolically Healthy versus Unhealthy Obesity

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 321
Author(s):  
Susana Rovira-Llopis ◽  
Rubén Díaz-Rúa ◽  
Carmen Grau-del Valle ◽  
Francesca Iannantuoni ◽  
Zaida Abad-Jimenez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Insulin Signalling ◽  
Cross Sectional Study ◽  
Differentially Expressed ◽  
Circulating Mirnas ◽  
Oxidative Stress Biomarkers ◽  
Cross Sectional ◽  
Metabolically Healthy Obese ◽  
Metabolically Healthy

Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pathways were upregulated in the MUO group. Among these miRNAs, hsa-miR-6796-5p and hsa-miR-4697-3p, which regulate oxidative stress, showed significant correlations with glucose, triglycerides, HbA1c and HDLc. Our results provide evidence of a pattern of differentially expressed miRNAs in obesity according to MetS, and identify those related to insulin resistance and lipid metabolism pathways.

Herpesvirus-Associated Proliferative Skin Disease in Frogs and Toads: Proposed Pathogenesis

2021 ◽  
pp. 030098582110063
Author(s):  
Francesco C. Origgi ◽  
Patricia Otten ◽  
Petra Lohmann ◽  
Ursula Sattler ◽  
Thomas Wahli ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rana Temporaria ◽  
Skin Lesions ◽  
Bufo Bufo ◽  
Careful Examination ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Cell Remodeling ◽  
Tissue Changes

A comparative study was carried out on common and agile frogs ( Rana temporaria and R. dalmatina) naturally infected with ranid herpesvirus 3 (RaHV3) and common toads ( Bufo bufo) naturally infected with bufonid herpesvirus 1 (BfHV1) to investigate common pathogenetic pathways and molecular mechanisms based on macroscopic, microscopic, and ultrastructural pathology as well as evaluation of gene expression. Careful examination of the tissue changes, supported by in situ hybridization, at different stages of development in 6 frogs and 14 toads revealed that the skin lesions are likely transient, and part of a tissue cycle necessary for viral replication in the infected hosts. Transcriptomic analysis, carried out on 2 naturally infected and 2 naïve common frogs ( Rana temporaria) and 2 naturally infected and 2 naïve common toads ( Bufo bufo), revealed altered expression of genes involved in signaling and cell remodeling in diseased animals. Finally, virus transcriptomics revealed that both RaHV3 and BfHV1 had relatively high expression of a putative immunomodulating gene predicted to encode a decoy receptor for tumor necrosis factor in the skin of the infected hosts. Thus, the comparable lesions in infected frogs and toads appear to reflect a concerted epidermal and viral cycle, with presumptive involvement of signaling and gene remodeling host and immunomodulatory viral genes.

scholarly journals 31. Influenza Vaccination During Pregnancy: A Descriptive Cross-sectional Survey of the Knowledge, Beliefs, and Attitudes of Mexican Gynecologists and Family Physicians

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S39-S39
Author(s):  
Erika Z Lopatynsky-Reyes ◽  
Sue Ann Costa-Clemens ◽  
Enrique Chacon-Cruz ◽  
Michael Greenberg
Keyword(s):  
Influenza Vaccination ◽  
Pregnant Women ◽  
Latin American ◽  
Vaccine Coverage ◽  
Family Physicians ◽  
Morbidity And Mortality ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Beliefs And Attitudes ◽  
In Pregnancy

Abstract Background Influenza in pregnancy is associated with elevated morbidity and mortality. Influenza vaccines are both safe and effective in pregnancy, supporting routine use in this population. Even though influenza vaccination in Mexico is recommended for pregnant women, there are no publications of influenza vaccine coverage in pregnancy. This is the first Latin American survey done only in physicians aiming to assess the knowledge, beliefs, and attitudes that Mexican Obstetrics-Gynecologists (OBG) and Family Physicians (FP) have towards influenza and influenza immunization during pregnancy. Methods A cross-sectional survey was conducted, both paper-based and online. The questionnaire was composed of 35 questions, which addressed general knowledge of influenza, recommendations for vaccination during pregnancy, and beliefs and attitudes concerning the acceptability of the vaccine in pregnant women. Results A total of 206 completed surveys were available, 98 (47.6%) from OBG, 108 (52.4%) from FP. Regarding current practicing medical institutions, 76 (37%), 69 (34%), 31 (14.5%), 30 (14.5%) reported working for the Mexican Institute of Social Security, Private Sector, Secretariat of Health, or a combination of all respectively, representing an estimated 2,472 daily pregnancy consultations. About a quarter (26.2%) reported not having a notion that influenza is more severe among pregnant women. More than half (51.5%) ignored the potential side effects of influenza infection on the fetus. The majority (56.8%) did not know when vaccination during pregnancy should occur. Pregnancy as a risk factor for developing influenza complications was known only in 48.1%. Also, 46.1 % believed that vaccination only confers protection to the mother, but not to the fetus. Nevertheless, 96.1% considered that immunization against influenza during pregnancy is a safe and effective preventive intervention. A results’ summary is shown in Figure-1. Conclusion Based on this survey, current knowledge of OBG and FP for influenza morbidity and mortality during pregnancy, and the importance of influenza vaccination in pregnant women, is poor. Mandatory recommendations to educate medical providers regarding influenza vaccination during pregnancy in Mexico are necessary, even as imperative for CME credits. Disclosures All Authors: No reported disclosures

scholarly journals Coverage of intermittent preventive treatment of malaria in pregnancy in four sub-Saharan countries: findings from household surveys

2020 ◽  
Author(s):  
Clara Pons-Duran ◽  
Mireia Llach ◽  
Charfudin Sacoor ◽  
Sergi Sanz ◽  
Eusebio Macete ◽  
...  
Keyword(s):  
Antenatal Care ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Malaria Prevention ◽  
Reproductive Age ◽  
Cluster Sampling ◽  
Household Surveys ◽  
Cross Sectional ◽  
Sub Saharan ◽  
In Pregnancy

Abstract Background Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is a key malaria prevention strategy in areas with moderate to high transmission. As part of the TIPTOP (Transforming IPT for Optimal Pregnancy) project, baseline information about IPTp coverage was collected in eight districts from four sub-Saharan countries: Democratic Republic of Congo (DRC), Madagascar, Mozambique and Nigeria. Methods Cross-sectional household surveys were conducted using a multistage cluster sampling design to estimate the coverage of IPTp and antenatal care attendance. Eligible participants were women of reproductive age who had ended a pregnancy in the 12 months preceding the interview and who had resided in the selected household during at least the past 4 months of pregnancy. Coverage was calculated using percentages and 95% confidence intervals. Results A total of 3911 women were interviewed from March to October 2018. Coverage of at least three doses of IPTp (IPTp3+) was 22% and 24% in DRC project districts; 23% and 12% in Madagascar districts; 11% and 16% in Nigeria local government areas; and 63% and 34% in Mozambique districts. In DRC, Madagascar and Nigeria, more than two-thirds of women attending at least four antenatal care visits during pregnancy received less than three doses of IPTp. Conclusions The IPTp3+ uptake in the survey districts was far from the universal coverage. However, one of the study districts in Mozambique showed a much higher coverage of IPTp3+ than the other areas, which was also higher than the 2018 average national coverage of 41%. The reasons for the high IPTp3+ coverage in this Mozambican district are unclear and require further study.

Matching the Heart to Heat-Induced Circulatory Load: Heat-Acclimatory Responses

Physiology ◽  
2003 ◽  
Vol 18 (6) ◽  
pp. 215-221 ◽  
Author(s):  
Michal Horowitz
Keyword(s):  
Heart Rate ◽  
Oxygen Demand ◽  
Heat Acclimation ◽  
Regulatory Proteins ◽  
Contractile Apparatus ◽  
Cardiac Efficiency ◽  
Cross Tolerance ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Cardiac Adaptation

Heat acclimation enhances cardiac efficiency by increasing stroke volume and decreasing heart rate. These adaptations involve biochemical changes in the contractile apparatus, switched on by altered expression of genes coding contractile and calcium-regulatory proteins and partially mediated by persistent low thyroxine. Heat acclimation also produces cross-tolerance to oxygen deprivation, thus reinforcing cardiac adaptation to oxygen demand/supply mismatching via energy-sparing pathways.

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