scholarly journals In Utero Exposure to 9-Tetrahydrocannabinol Leads to Postnatal Catch-up Growth and Dysmetabolism in the Adult Rat Liver

2021 ◽  
Author(s):  
Shelby Louise Oke ◽  
Kendrick Lee ◽  
Rosemary Papp ◽  
Steven R. Laviolette ◽  
Daniel B. Hardy
Keyword(s):  
Mitochondrial Dysfunction ◽  
Animal Studies ◽  
Weight Ratio ◽  
Wistar Rat ◽  
Hepatic Function ◽  
Fetal Life ◽  
Adult Rat ◽  
Catch Up ◽  
By Catch

Rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to 9-tetrahydrocannabinol (9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that 9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg 9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to 9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, 9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACC, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, was also observed in these 9-THC-exposed offspring. Collectively, these findings indicate that prenatal 9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.

scholarly journals In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver

2021 ◽  
Vol 22 (14) ◽  
pp. 7502
Author(s):  
Shelby L. Oke ◽  
Kendrick Lee ◽  
Rosemary Papp ◽  
Steven R. Laviolette ◽  
Daniel B. Hardy
Keyword(s):  
Mitochondrial Dysfunction ◽  
Animal Studies ◽  
Weight Ratio ◽  
Wistar Rat ◽  
Hepatic Function ◽  
Fetal Life ◽  
Adult Rat ◽  
Catch Up ◽  
By Catch

The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.

scholarly journals Perinatal protein restriction with postnatal catch-up growth leads to elevated p66Shc and mitochondrial dysfunction in the adult rat liver

Reproduction ◽  
2020 ◽  
Vol 159 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Shelby L Oke ◽  
Gurjeev Sohi ◽  
Daniel B Hardy
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Control Diet ◽  
Protein Abundance ◽  
Low Protein ◽  
Catch Up ◽  
By Catch

Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet throughout gestation. Offspring born to control dams received a control diet in postnatal life, while MPR offspring remained on a LP diet (LP1) or received a control diet post weaning (LP2) or at birth (LP3). At four months, LP2 offspring exhibited increased protein abundance of both p66Shc and the cis-trans isomerase PIN1. This was further associated with aberrant markers of oxidative stress (i.e. elevated 4-HNE, SOD1 and SOD2, decreased catalase) and aerobic metabolism (i.e., increased phospho-PDH and LDHa, decreased complex II, citrate synthase and TFAM). We further demonstrated that tunicamycin-induced ER stress in HepG2 cells led to increased p66Shc protein abundance, suggesting that ER stress may underlie the programmed effects observed in vivo. In summary, because these defects are exclusive to adult LP2 offspring, it is possible that a low protein diet during perinatal life, a period of liver plasticity, followed by catch-up growth is detrimental to long-term mitochondrial function.

Fetal programming of hypertension

2006 ◽  
Vol 290 (1) ◽  
pp. R1-R10 ◽  
Author(s):  
Barbara T. Alexander
Keyword(s):  
Fetal Programming ◽  
Animal Studies ◽  
Subsequent Development ◽  
Epidemiological Studies ◽  
Fetal Life ◽  
Adaptive Responses ◽  
Renal Functions ◽  
Regulatory Systems ◽  
Physiological Alterations

Numerous epidemiological studies suggest an inverse relationship between low birth weight (LBW) and hypertension, an observation now supported by numerous animal studies. The mechanisms linking LBW and hypertension appear to be multifactorial and involve alterations in the normal regulatory systems and renal functions involved in the long-term control of arterial pressure. Recent studies using animal models of fetal programming suggest that programming during fetal life occurs in response to an adverse fetal environment and results in permanent adaptive responses that lead to structural and physiological alterations and the subsequent development of hypertension. This review summarizes the adaptive responses observed in the different models used to induce a suboptimal fetal environment and discusses insights into the mechanisms mediating the fetal programming of hypertension.

PENGARUH INFRASTRUKTUR SECARA SPASIAL TERHADAP KONVERGENSI PERTUMBUHAN EKONOMI DI INDONESIA

INFO ARTHA ◽  
2017 ◽  
Vol 1 ◽  
pp. 17-28
Author(s):  
Anisa Fahmi
Keyword(s):  
Economic Growth ◽  
Regional Economics ◽  
Developed Countries ◽  
Road Infrastructure ◽  
Long Run ◽  
Catch Up ◽  
The Developed Countries ◽  
Positive Effect ◽  
Neoclassical Growth Theory

Motivated by inter-regional disparities condition that occurs persistently, this study examines the Indonesian economy in the long run in order to know whether it tends to converge or diverge. This convergence is based on the Solow Neoclassical growth theory assuming the existence of diminishing returns to capital so that when the developed countries reach steady state conditions, developing countries will continuously grow up to 'catch-up' with developed countries. Based on regional economics perspective, each region can not be treated as a stand-alone unit,therefore, this study also focuses on the influence of spatial dependency and infrastructure. Economical and political situations of a region will influence policy in that region which will also have an impact to the neighboring regions. The estimation results of spatial cross-regressive model using fixed effect method consistently confirmed that the Indonesian economy in the long term will likely converge with a speed of 8.08 percent per year. Other findings are road infrastructure has a positive effect on economic growth and investment and road infrastructure are spatially showed a positive effect on economic growth. In other words, the investment and infrastructure of a region does not only affect the economic growth of that region but also to the economy of the contiguous regions. 

Gestational exposure to Δ9-THC impacts ovarian follicular dynamics and angiogenesis in adulthood in Wistar rats

2021 ◽  
pp. 1-5
Author(s):  
Annia A. Martínez-Peña ◽  
Kendrick Lee ◽  
James J. Petrik ◽  
Daniel B. Hardy ◽  
Alison C. Holloway
Keyword(s):  
Reproductive Health ◽  
Cannabis Sativa ◽  
Follicular Development ◽  
Angiogenic Factor ◽  
Postnatal Life ◽  
Adult Rat ◽  
Female Reproductive Health ◽  
Gestational Exposure ◽  
Follicular Dynamics

Abstract With the legalization of marijuana (Cannabis sativa) and increasing use during pregnancy, it is important to understand its impact on exposed offspring. Specifically, the effects of Δ-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component of cannabis, on fetal ovarian development and long-term reproductive health are not fully understood. The aim of this study was to assess the effect of prenatal exposure to Δ9-THC on ovarian health in adult rat offspring. At 6 months of age, Δ9-THC-exposed offspring had accelerated folliculogenesis with apparent follicular development arrest, but no persistent effects on circulating steroid levels. Ovaries from Δ9-THC-exposed offspring had reduced blood vessel density in association with decreased expression of the pro-angiogenic factor VEGF and its receptor VEGFR-2, as well as an increase in the anti-angiogenic factor thrombospondin 1 (TSP-1). Collectively, these data suggest that exposure to Δ9-THC during pregnancy alters follicular dynamics during postnatal life, which may have long-lasting detrimental effects on female reproductive health.

scholarly journals When a Neonate Is Born, So Is a Microbiota

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 148
Author(s):  
Alessandra Coscia ◽  
Flaminia Bardanzellu ◽  
Elisa Caboni ◽  
Vassilios Fanos ◽  
Diego Giampietro Peroni
Keyword(s):  
Bacterial Colonization ◽  
Perinatal Period ◽  
Delivery Mode ◽  
Fetal Life ◽  
Assisted Reproduction Techniques ◽  
Neonatal Nutrition ◽  
Short And Long Term ◽  
Number Of Bacteria

In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one’s life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the “sterile womb”. Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject.

scholarly journals Recent Developments in Rodent Models of High-Fructose Diet-Induced Metabolic Syndrome: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2497
Author(s):  
Alvin Man Lung Chan ◽  
Angela Min Hwei Ng ◽  
Mohd Heikal Mohd Yunus ◽  
Ruszymah Bt Hj Idrus ◽  
Jia Xian Law ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Animal Studies ◽  
18Th Century ◽  
Disease Model ◽  
Hepatic Function ◽  
Chronic Illnesses ◽  
Paradigm Shifts ◽  
Response Factors ◽  
High Fructose ◽  
Recent Developments

Metabolic syndrome (MetS) is the physiological clustering of hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, and insulin resistance. The MetS-related chronic illnesses encompass obesity, the cardiovascular system, renal operation, hepatic function, oncology, and mortality. To perform pre-clinical research, it is imperative that these symptoms be successfully induced and optimized in lower taxonomy. Therefore, novel and future applications for a disease model, if proven valid, can be extrapolated to humans. MetS model establishment is evaluated based on the significance of selected test parameters, paradigm shifts from new discoveries, and the accessibility of the latest technology or advanced methodologies. Ultimately, the outcome of animal studies should be advantageous for human clinical trials and solidify their position in advanced medicine for clinicians to treat and adapt to serious or specific medical situations. Rodents (Rattus norvegicus and Mus musculus) have been ideal models for mammalian studies since the 18th century and have been mapped extensively. This review compiles and compares studies published in the past five years between the multitude of rodent comparative models. The response factors, niche parameters, and replicability of diet protocols are also compiled and analyzed to offer insight into MetS-related disease-specific modelling.

scholarly journals Assessment of Electrospun Pellethane-Based Scaffolds for Vascular Tissue Engineering

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3678
Author(s):  
Vera Chernonosova ◽  
Alexandr Gostev ◽  
Ivan Murashov ◽  
Boris Chelobanov ◽  
Andrey Karpenko ◽  
...  
Keyword(s):  
Vascular Tissue ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Wistar Rat ◽  
Graft Occlusion ◽  
Suitable Candidate ◽  
Large Animals ◽  
Cell Adhesion And Proliferation

We examined the physicochemical properties and the biocompatibility and hemocompatibility of electrospun 3D matrices produced using polyurethane Pellethane 2363-80A (Pel-80A) blends Pel-80A with gelatin or/and bivalirudin. Two layers of vascular grafts of 1.8 mm in diameter were manufactured and studied for hemocompatibility ex vivo and functioning in the infrarenal position of Wistar rat abdominal aorta in vivo (n = 18). Expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar diameter were implanted as a control (n = 18). Scaffolds produced from Pel-80A with Gel showed high stiffness with a long proportional limit and limited influence of wetting on mechanical characteristics. The electrospun matrices with gelatin have moderate capacity to support cell adhesion and proliferation (~30–47%), whereas vascular grafts with bivalirudin in the inner layer have good hemocompatibility ex vivo. The introduction of bivalirudin into grafts inhibited platelet adhesion and does not lead to a change hemolysis and D-dimers concentration. Study in vivo indicates the advantages of Pel-80A grafts over ePTFE in terms of graft occlusion, calcification level, and blood velocity after 6 months of implantation. The thickness of neointima in Pel-80A–based grafts stabilizes after three months (41.84 ± 20.21 µm) and does not increase until six months, demonstrating potential for long-term functioning without stenosis and as a suitable candidate for subsequent preclinical studies in large animals.

scholarly journals Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life

2021 ◽  
Author(s):  
Kendrick Lee ◽  
Steven R. Laviolette ◽  
Daniel B. Hardy
Keyword(s):  
Body Weight ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Cardiac Remodelling ◽  
Long Term Effects ◽  
Catch Up ◽  
First Time ◽  
Impaired Cardiac Function ◽  
In Pregnancy

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.

scholarly journals Influence of Intermittent Parathyroid Hormone (PTH) Administration on the Outcomes of Orthodontic Tooth Movement—A Systematic Review

2021 ◽  
Vol 11 (11) ◽  
pp. 5268
Author(s):  
Zohaib Khurshid ◽  
Faris Yahya Asiri
Keyword(s):  
Parathyroid Hormone ◽  
Animal Studies ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Inclusion Criteria ◽  
Medical Subject Headings ◽  
Periodontal Tissues ◽  
Minimal Bias ◽  
Intermittent Pth

Objective: The aim of this review is to summarize the effects of local and systemic PTH administration on periodontal tissues during orthodontic tooth movement. Materials and methods: An electronic search was conducted on the following databases: PubMed/MEDLINE, Google Scholar, SCOPUS and Embase. On PubMed/MEDLINE, the Medical Subject Headings (MeSH) keywords used were: “orthodontic tooth movement” OR (“tooth” (All Fields) AND “tooth movement” (All Fields)) OR “tooth movement” (All Fields)) AND (“parathyroid hormone”); all studies included using CONSORT. Results: After elimination of duplicates and articles not meeting our inclusion criteria, seven animal studies were included in this review. Although the majority of the studies suggest that PTH may a have a favorable outcome on OTM, most studies were found to have several sources of bias. Conclusion: Animal studies with minimal bias and long-term clinical studies are needed to ascertain the efficacy of intermittent PTH administration in improving the rate and retention of OTM.

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