Periconceptional alcohol consumption causes fetal growth restriction and increases glycogen accumulation in the late gestation rat placenta

Gardebjer, Emelie M; Cuffe, James; Pantaleon, Marie; Wlodek, Mary E.; Moritz, Karen M.

doi:10.1016/j.placenta.2013.10.008

Cited by 84 publications

(162 citation statements)

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“…What the risks of lower levels of consumption are remains debated 100 . Animal models indicate that alterations in fetal growth occur even with brief periconceptional alcohol exposure 101 and even low levels of alcohol consumption during the first trimester affect craniofacial development in humans 102 .…”

Section: Persistence Of Adolescent Assets and Risksmentioning

confidence: 99%

Adolescence and the next generation

Patton

Olsson

Skirbekk

et al. 2018

Nature

288

228

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Adolescent growth and social development shape the early development of offspring from preconception through to the post-partum period through distinct processes in males and females. At a time of great change in the forces shaping adolescence, including the timing of parenthood, investments in today’s adolescents, the largest cohort in human history, will yield great dividends for future generations.

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Section: Persistence Of Adolescent Assets and Risksmentioning

confidence: 99%

Adolescence and the next generation

Patton

Olsson

Skirbekk

et al. 2018

Nature

288

228

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“…Animal studies have successfully recapitulated the three main diagnostic feature of FAS: abnormal neural development , growth retardation (Kaminen-Ahola et al, 2010b;Probyn et al, 2012;Gardebjer et al, 2014) and craniofacial abnormalities (Sulik et al, 1981;Anthony et al, 2010;Kaminen-Ahola et al, 2010b). In addition to these, the usage of animal models has allowed for the investigation of a wide range of other phenotypes resultant of prenatal ethanol exposure: impairments to behaviour (Sanchez Vega et al, 2013), glucose metabolism (Harper et al, 2014), adiposity (Dobson et al, 2012), renal (Gray et al, 2010) and cardiovascular (Ren et al, 2002) function, lung development (Probyn et al, 2013), hypothalamic-pituitary-adrenal function (Lan et al, 2009), and even osteoarthritis risk (Ni et al, 2015).…”

Section: Evidence In Animal Modelsmentioning

confidence: 99%

“…One of these models utilised pregnant Sprague-Dawley rats subjected to a periconceptional ethanol exposure (ad libitum access to 12.5% v/v ethanol in a liquid diet from four days before conception until four days after conception) (Gardebjer et al, 2014). This periconceptional exposure alone was sufficient to result in fetal growth restriction at gestational day 20 (Gardebjer et al, 2014), as well as impairments in glucose homeostasis at 6 months of age (Gardebjer et al, 2015). The challenge inherent in periconceptional animal models that rely on voluntary consumption is that as well as the exposure to the dam, the stud is often exposed too, and thus it can be difficult to discern with confidence maternal versus paternal effects.…”

Section: Consequences Of Early Gestational Exposure To Ethanol And/ormentioning

confidence: 99%

“…These phenotypes include abnormal neural development and behaviour (Sanchez Vega et al, 2013;Zhang et al, 2015), growth retardation (Kaminen-Ahola et al, 2010b;Probyn et al, 2012;Gardebjer et al, 2014) and craniofacial abnormalities (Sulik et al, 1981;Anthony et al, 2010;Kaminen-Ahola et al, 2010b), metabolic perturbations (Dobson et al, 2012;Harper et al, 2014), as well as the abnormal development and function of the renal, cardiovascular and pulmonary systems (Ren et al, 2002;Gray et al, 2010;Probyn et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

Yamada¹

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The in utero environment is a critical determinant of the immediate and future health of the developing fetus. In Australia, two of the most commonly used drugs during pregnancy are alcohol and nicotine. Prolonged periods of gestational exposure to alcohol and nicotine, separately, have been associated with a range of adverse outcomes in the offspring, in both humans and experimental animal models. The consequences of ethanol and nicotine exposure restricted to early gestation on resultant offspring are poorly characterised, and few animal models exist to build greater understanding. Moreover, the immediate molecular changes associated with exposures to ethanol and/or nicotine restricted to early gestation has yet to be described.This thesis utilised mouse models of early gestational ethanol and/or nicotine exposure to explore the impact of each of these exposures on offspring growth, as well as their associated transcriptional and epigenetic changes. In each model, pregnant C57BL/6 dams were provided with ad libitum access to solutions of 10% ethanol and/or 100 µg/ml nicotine from fertilisation (0.5 dpc) to midgestation (8.5 dpc). The exposure window utilised in each of the models is developmentally equivalent to the first three to four weeks of a human pregnancy.Previously, our laboratory identified reduced growth, microcephaly, and gene expression changes in the liver and hippocampus of the postnatal offspring of the model of prenatal ethanol exposure utilised in this thesis. In contrast, at mid-gestation (9.5 dpc), there was no evidence of developmental delay (somite number), reduced growth (crown-rump length), or microcephaly.Further, a genome-wide gene expression microarray (targeting 30 855 genes) and a screen of the expression of 641 microRNAs, identified only one gene (Bcl11b) as differentially expressed in male 9.5 dpc whole embryos following the ethanol exposure. These data suggest that there is a delay between the ethanol exposure and the onset of adverse phenotypes -arguing that the embryo is somehow able to form a memory of the ethanol exposure. The absence of widespread transcriptional changes suggests that changes in embryonic mRNA and microRNA expression are unlikely to be major contributors to the memory of the exposure.A early gestational model of nicotine exposure was newly established in this thesis. This nicotine exposure resulted in an average serum cotinine (metabolite of nicotine) concentration similar to that reported in humans who smoke 10 to 15 cigarettes per day. This exposure was sufficient to induce a reduction in body size both at mid-gestation and postnatally, but not at late gestation. Furthermore, the increased expression of Zscan10 in the whole male 9.5 dpc embryo was identified and validated across multiple cohorts. Zscan10 encodes for a transcription factor expressed throughout development, with a proposed role in the regulation of progenitor cells. The increased expression of Zscan10 in the nicotine-exposed embryos was associated with a reduction in DNA methylation ...

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“…Therefore, although ethanol has been shown to acutely reduce fetal and maternal blood flow to the placenta in humans and other animal models [6][7][8] , the alterations to placental function observed here more likely result from longer-term developmental consequences of ethanol exposure during the periconceptional period. Prior rodent studies have identified the influence of periconceptional ethanol exposure on subsequent trophoblast survival, gene expression, and zonal distribution at later gestational ages 32,33 . Notably, in rodents, ethanol exposure early in pregnancy is associated with reduced trophoblast invasion of the spiral arteries and altered placental vascular development associated with impaired fetal growth [34][35][36] .…”

Section: Commentmentioning

confidence: 99%

28: First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

Schabel

Wang

et al. 2017

American Journal of Obstetrics and Gynecology

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Objective-Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol linking altered placental function to impaired fetal development remain areas of active research. Recently, we developed MRI techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T 2 *, and perfusion using dynamic contrast-enhanced (DCE) MRI. The objective of this study was to evaluate the effects of first trimester alcohol exposure on macaque placental function and to characterize fetal brain development, in vivo.Study Design-Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to orally self-administer either 1.5g/kg/day of a 4% ethanol solution (equivalent to 6 drinks/day) or an isocaloric control fluid from pre-conception until gestational day 60 (G60, term is G168). All underwent Doppler ultrasound (D-US) followed by MRI consisting of T 2 * and DCE measurements. D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors report no conflicts of interest.Presented orally at the 37 th Society of Maternal Fetal Medicine Annual Meetings in Las Vegas, Nevada, January 23-28 th , 2017Reprints will not be available. HHS Public Access Author Manuscript Author Manuscript Author ManuscriptAuthor Manuscript blood flow (cQuta) and placental volume blood flow (cQuv). After non-invasive imaging, animals underwent C-section delivery for placenta collection and fetal necropsy at G110 (n=6) or G135 (n=6).Results-Fetal weight and biparietal diameter were significantly smaller in ethanol exposed compared to controls at G110. By D-US, cQuta was decreased (p=0.1) and cQuv was significantly lower (p=0.04) at both G110 and G135 in ethanol exposed versus control animals. A significant reduction in placental blood flow was evident by DCE-MRI. As we demonstrated recently, T 2 * values vary throughout the placenta, and reveal gradients in blood deoxyhemoglobin concentration ranging from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 * throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol exposed vs. control at G110 (p=0.02). Fetal brain measurements indicated impaired grow...

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Periconceptional alcohol consumption causes fetal growth restriction and increases glycogen accumulation in the late gestation rat placenta

Cited by 84 publications

References 45 publications

Adolescence and the next generation

Adolescence and the next generation

A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

28: First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

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