Vascular effects of maternal alcohol consumption

Maternal alcohol consumption during pregnancy is a significant field of scientific exploration primarily because of its negative effects on the developing fetus, which is specifically defined as fetal alcohol spectrum disorders. Though the effects on the mother are less explored compared with those on the fetus, alcohol produces multiple effects on the maternal vascular system. Alcohol has major effects on systemic hemodynamic variables, endocrine axes, and paracrine factors regulating vascular resistance, as well as vascular reactivity. Alcohol is also reported to have significant effects on the reproductive vasculature including alterations in blood flow, vessel remodeling, and angiogenesis. Data presented in this review will illustrate the importance of the maternal vasculature in the pathogenesis of fetal alcohol spectrum disorders and that more studies are warranted in this field.     

Developing ways of reducing allograft immunogenicity.

Heavy alcohol consumption by the mother during pregnancy has long been suspected of being a risk factor for abnormalities in the fetus or infant. Only during the last decade have these assumptions been supported by scientific studies. A clustering of fetal defects observed in some cases has been labelled the fetal alcohol syndrome. The syndrome involves prenatal and postnatal growth retardation, central nervous system involvement and craniofacial abnormalities, some of which are characteristic of the syndrome. Fetal alcohol syndrome is relatively rare, affecting from 1 in 300 to 1 in 2000 infants; approximately 450 cases have been reported since the syndrome was identified. Despite this rarity, however, heavy alcohol consumption is an important risk factor during pregnancy. A review of the current literature indicates that in animals alcohol in high doses is embryotoxic and teratogenic, the heavy drinking is not uncommon before and during pregnancy and that the fetal alcohol syndrome and other effects on the fetus associated with alcohol abuse appear with significant frequency among mothers who drink heavily. Heavy alcohol consumption is a perinatal risk factor that not only can be detected by the physician, but also can be reduced in concerned, cooperative patients. Thus, awareness of this problem gives health care personnel an opportunity to help in the prevention of abnormal outcomes of pregnancy.     

Effects of alcohol on the fetus: impact and prevention.

In the spectrum of adverse effects on the fetus or infant associated with maternal drinking during pregnancy the most dramatic is the fetal alcohol syndrome, a pattern of malformation that has been associated with maternal alcohol abuse. Other undesirable outcomes of pregnancy linked to alcohol exposure in utero include growth deficiency, major and minor anomalies, decrements in mental and motor performance, and fetal and perinatal wastage. Alcohol, like other teratogens, does not uniformly affect all those exposed to it. Rather, there seems to be a continuum of effects of alcohol on the fetus with increasingly severe outcomes generally associated with higher intakes of alcohol by the mother. The cost of fetal damage associated with alcohol exposure is very high. A program to decrease the incidence of fetal alcohol effects is therefore imperative. The cornerstone of such a program must be not only education of the public but also careful training of all professionals who provide health care for pregnant women.     

Fetal alcohol syndrome: an assessment of the field

Fetal exposure to alcohol is the major known cause of mental retardation in the Western world. For more than half of the 20th century, the placenta was widely believed to be an effective barrier against environmental agents. The discovery that offspring of pregnant women who were exposed to German measles or administered thalidomide were often malformed raised awareness that teratogens could be any environmental agent, including viruses and drugs, that caused abnormal development. Alcohol was not identified as a teratogen until the 1970s. Fetal exposure to alcohol can cause fetal alcohol syndrome (FAS), which is characterized by specific physical traits and central nervous system dysfunctions. The development of animal model systems has facilitated our study of the effects of fetal alcohol exposure and the elucidation of the mechanisms involved in alcohol-induced abnormal development. Despite our current understanding of the effects of fetal alcohol exposure, the occurrence of FAS and associated fetal alcohol spectrum disorders is still widespread and the associated health-care costs are staggering. This symposium provides an up-to-date analysis of fetal exposure to alcohol and FAS. It is directed not only to investigators working in the field but to a diverse group of scientists working in the biological and biomedical fields to stimulate cross-disciplinary awareness, interest, and collaboration.     

Prenatal Alcohol Exposure Increases Postnatal Acceptability of Nicotine Odor and Taste in Adolescent Rats

Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol''s bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine''s odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams'' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our results suggest broader implications related to the consequence of fetal exposure with one substance of abuse and initial acceptability of others.     

Prenatal effects of alcohol on growth: a brief overview

Intrauterine growth retardation is the most reliable consequence of prenatal exposure to alcohol in both humans and animals. The decrease in fetal growth is caused by alcohol, not by congeners present in alcoholic beverages. The most likely hypothesis whereby alcohol decreases growth is via hypoxia, which interferes with cellular processes that require oxygen to function adequately, e.g., placental transport and protein synthesis. The third trimester of pregnancy is when alcohol exerts its greatest impact on fetal growth.     

Zinc,ethanol, and lipid peroxidation in adult and fetal rats

Studies were performed on adult and fetal rats receiving either a zinc-deficient (<0.5 ppm) diet and/or ethanol (20%) throughout pregnancy. Liver zinc levels were depressed in fetuses exposed toin utero zinc deficiency, but brain zinc levels were unchanged. Ethanol had no effect on the concentration of zinc in the several fetal and adult tissues studies. Lipid peroxidation, as measured by endogenous levels of malondialdehyde (MDA) increased following food restriction, zinc improverishment, and alcoholism in adult and fetal livers, but not in fetal brains. Generally, levels of MDA were highest when both zinc deficiency and the ingestion of alcohol occurred concurrently. Glutathione (GSH) was depressed by zinc restriction in several adult and fetal tissues, but not in the fetal brain. Ethanol alone had no effect on GSH levels. The activity of the enzyme glutathione peroxidase (GSH-Px) was not changed in either organism by alcohol or zinc deficiency. Overall, the data point to increased lipid peroxidation in maternal and fetal rat tissues following zinc depletion and/or treatment with alcohol and draw attention to the apparent vulnerability of the fetal liver toin utero alcoholism. By contrast, the fetal brain seems to be especially resistant to alcohol and zinc-related lipoperoxidation. An association is suggested between the increased lipoperoxidation accompanying zinc deficiency and reduced levels of GSH, but this does not appear to relate to changes in the activity of GSH-Px. A similar relationship is not evident with respect to the increased levels of MDA in fetal and adult livers following chronic alcohol intoxication. A possible basis for the zinc-GSH interaction is discussed.     

Effect of maternal alcohol consumption on the fetal thyroid in the rat

To investigate the effect of maternal alcohol consumption on the development of the fetal thyroid gland, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On Days 17, 18, 19, and 20 of gestation, the fetuses were weighed and the fetal thyroids were removed for histometric observation. On Days 19 and 20, the fetal thyroids of alcohol-exposed fetuses weighed significantly less than those of the two control groups, but more than the control thyroids 1 day earlier. Maternal alcohol consumption caused a significant decrease in both the follicular cell height and the follicle diameter of the fetal thyroid on all days examined. In the alcohol group on Days 19 and 20 of gestation, the cell height was less than, and the follicle diameter was approximately equal to those in the two controls 2 days earlier. These results indicate that, as a consequence of maternal alcohol consumption, growth of the fetal thyroid gland is retarded, and there are indications of fetal hypothyroidism, as seen from the histometric data. This latter is suggestive of a retarded thyrotropic activity of the fetal pituitary gland.     

Effects of l-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and l-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal l-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. l-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, l-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.     

Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function

Alcohol abuse is known to result in clinical abnormalities of endocrine function and neuroendocrine regulation. However, most studies have been conducted on males. Only recently have studies begun to investigate the influence of alcohol on endocrine function in females and, more specifically, endocrine function during pregnancy. Alcohol-induced endocrine imbalances may contribute to the etiology of fetal alcohol syndrome. Alcohol crosses the placenta and can directly affect developing fetal cells and tissues. Alcohol-induced changes in maternal endocrine function can disrupt maternal-fetal hormonal interactions and affect the female's ability to maintain a successful pregnancy, thus indirectly affecting the fetus. In this review, we focus on the adverse effects of prenatal alcohol exposure on neuroendocrine and immune function, with particular emphasis on the hypothalamic-pituitary-adrenal (HPA) axis and the concept of fetal programming. The HPA axis is highly susceptible to programming during fetal development. Early environmental experiences, including exposure to alcohol, can reprogram the HPA axis such that HPA tone is increased throughout life. We present data that demonstrate that maternal alcohol consumption increases HPA activity in both the maternal female and the offspring. Increased exposure to endogenous glucocorticoids throughout the lifespan can alter behavioral and physiologic responsiveness and increase vulnerability to illnesses or disorders later in life. Alterations in immune function may be one of the long-term consequences of fetal HPA programming. We discuss studies that demonstrate the adverse effects of alcohol on immune competence and the increased vulnerability of ethanol-exposed offspring to the immunosuppressive effects of stress. Fetal programming of HPA activity may underlie some of the long-term behavioral, cognitive, and immune deficits that are observed following prenatal alcohol exposure.     

Abortion is incommensurable with fetal alcohol syndrome

A recent article argued for the immorality of abortion regardless of personhood status by comparing the impairment caused by fetal alcohol syndrome to the impairment caused by abortion. I argue that two of the premises in this argument fail and that, as such, one cannot reasonably attribute moral harms to abortion on the basis of the moral harms caused by fetal alcohol syndrome. The impairment argument relies on an inconsistent instantiation, which undermines the claim that personhood is irrelevant, and it does not fulfill its own ceteris paribus clause, which demands that no additional benefit be gained from abortion that would not be gained from causing fetal alcohol syndrome.     

The impairment argument for the immorality of abortion: A reply

In his recent article Perry Hendricks presents what he calls the impairment argument to show that abortion is immoral. To do so, he argues that to give a fetus fetal alcohol syndrome is immoral. Because killing the fetus impairs it more than giving it fetal alcohol syndrome, Hendricks concludes that killing the fetus must also be immoral. Here, I claim that killing a fetus does not impair it in the way that giving it fetal alcohol syndrome does. By examining the reason why giving a fetus this condition is wrong, I conclude that the same reasoning, on common pro‐choice accounts, does not apply to killing the fetus. Accordingly, Hendricks's argument does not succeed in showing abortion is immoral.     

Binge alcohol exposure in the second trimester attenuates fetal cerebral blood flow response to hypoxia.

Alcohol is detrimental to the developing brain and remains the leading cause of mental retardation in developed countries. The mechanism of alcohol brain damage remains elusive. Studies of neurological problems in adults have focused on alcohol's cerebrovascular effects, because alcoholism is a major risk factor for stroke and cerebrovascular injuries. However, few studies have examined similar cerebrovascular effects of fetal alcohol exposure. We examined the effect of chronic binge alcohol exposure during the second trimester on fetal cerebrovascular and metabolic responses to hypoxia in near-term sheep and tested the hypothesis that fetal alcohol exposure would attenuate cerebrovascular dilation to hypoxia. Pregnant ewes were infused with alcohol (1.5 g/kg) or saline intravenously at 60-90 days of gestation (full term = 150 days). At 125 days of gestation, we measured fetal cerebral blood flow (CBF) and oxygen metabolism at baseline and during hypoxia. Maternal blood alcohol averaged 214 +/- 5.9 mg/dl immediately after the 1.5-h infusion, with similar values throughout the month of infusion. Hypoxia resulted in a robust increase in CBF in saline-infused fetuses. However, the CBF response to hypoxia in fetuses chronically exposed to alcohol was significantly attenuated. Cerebral oxygen delivery decreased in both groups of fetuses during hypoxia but to a greater degree in the alcohol-exposed fetuses. Prenatal alcohol exposure during the second trimester attenuates cerebrovascular responses to hypoxia in the third trimester. Altered cerebrovascular reactivity might be one mechanism for alcohol-related brain damage and might set the stage for further brain injury if a hypoxic insult occurs.     

The effects of alcohol on fetal development

Prenatal exposure to alcohol has profound effects on many aspects of fetal development. Although alterations of somatic growth and specific minor malformations of facial structure are most characteristic, the effects of alcohol on brain development are most significant in that they lead to substantial problems with neurobehavioral development. Since the initial recognition of the fetal alcohol syndrome (FAS), a number of important observations have been made from studies involving both humans and animals. Of particular importance, a number of maternal risk factors have been identified, which may well be of relevance relative to the development of strategies for prevention of the FAS as well as intervention for those who have been affected. These include maternal age >30 years, ethnic group, lower socioeconomic status, having had a previously affected child, maternal under-nutrition, and genetic background. The purpose of this review is to discuss these issues as well as to set forth a number of questions that have not adequately been addressed relative to alcohol's effect on fetal development. Of particular importance is the critical need to identify the full spectrum of structural defects associated with the prenatal effects of alcohol as well as to establish a neurobehavioral phenotype. Appreciation of both of these issues is necessary to understand the full impact of alcohol on fetal development.     

Vasoactive intestinal peptide mRNA and immunoreactivity are decreased in fetal alcohol syndrome model

Vasoactive intestinal peptide (VIP) regulates growth in the early post-implantation embryo. Previous work has demonstrated that peptide agonists (SALLRSIPA and NAPVSIPQ) from downstream mediators that are regulated by VIP were able to prevent the alcohol-induced fetal death, growth restriction and microcephaly associated with fetal alcohol syndrome. Here we evaluated the role of VIP in this mouse model of fetal alcohol syndrome, to determine if fetal or maternal levels of VIP are altered. In addition, we evaluated whether peptide treatment would alter the effects of alcohol on VIP levels. Treatment groups included control, alcohol, and alcohol+peptides. VIP levels were measured with enzyme immunoassay [EIA] (Peninsula Laboratories, Belmont, CA). Quantitation of VIP expression was measured with rt-PCR using mimic cDNA primers. Embryo/decidual VIP levels were similar in control and alcohol-treated groups 6 h after treatment. However, in the embryo/deciduas at 12 and 24 h, VIP levels were below the EIA's detection limit in the alcohol-treated groups, and significantly lower than the control or peptide-pretreated groups (p<0.05). Maternal cortex VIP levels were undetectable and significantly lower in the alcohol-treated group than control or peptide+alcohol group at 6 and 12 h (p<0.001). VIP mRNA expression was quantitated in the embryo and deciduas, with a significant decline noted at 6 h to 58% of control levels (p=0.02). Pretreatment with the peptides attenuated the alcohol-induced decrease in VIP mRNA. These studies demonstrate that treatment with alcohol can decrease the expression and immunoreactivity of VIP in both maternal and fetal tissues. This alcohol-induced loss of a recognized regulator of embryonic growth and differentiation may contribute to the sequelae of toxicity observed in fetal alcohol syndrome.     

Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells.     

Effects of alcohol (ethanol) on the fetus

Alcohol (ethanol) use during pregnancy can produce a wide spectrum of effects in the developing embryo/fetus that are dependent on the maternal drinking pattern. The effects of chronic ethanol exposure on the developing conceptus are reviewed with primary focus on ethanol teratogenesis, manifesting in the human as the fetal alcohol syndrome or fetal alcohol effects. The effects of acute ethanol exposure on the near-term fetus are described, including suppressed fetal breathing movements, electrocorticographic (ECoG) activity and electrooculographic (EOG) activity. The ethanol-induced suppression of fetal breathing movements is a very sensitive index of acute exposure of the near-term fetus to ethanol, and appears to involve a direct mechanism of action rather than an indirect mechanism involving suppression of electrocortical activity. The disposition of ethanol and its pharmacologically active proximate metabolite, acetaldehyde, and the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the near-term maternal-fetal unit are described, and a pharmacokinetic model is proposed. The effects of short-term ethanol exposure on the near-term fetus include the development of tolerance to the ethanol-induced suppression of fetal breathing movements, low-voltage ECoG activity and EOG activity. The development of tolerance occurs more rapidly to the latter two fetal biophysical activities. The mechanism of tolerance development appears to be pharmacodynamic (functional) in nature, as there is no increase in the rate of ethanol elimination from the maternal-fetal unit. The role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of fetal breathing movements is described. In the near-term fetus, there is a direct relationship between fetal blood ethanol concentration and fetal plasma PGE2 concentration, and an inverse relationship between the incidence of fetal breathing movements and each of fetal plasma and fetal cerebrospinal fluid (CSF) PGE2 concentrations. Indomethacin, a PG synthetase inhibitor, selectively blocks and reverses the ethanol-induced suppression of fetal breathing movements. These data support the postulates that the ethanol-induced suppression of fetal breathing movements is mediated by increased PGE2 concentration in the near-term fetus and that the ability of indomethacin to antagonize the ethanol-induced suppression of fetal breathing movements is due to its biochemical action to decrease fetal PGE2 concentration.(ABSTRACT TRUNCATED AT 400 WORDS)     

怀孕前后酒精摄入对雌鼠植入前胚胎DNA甲基化模式建立的影响

女性怀孕前后饮酒会对胎儿的发育及神经系统造成不利影响,称为“胎儿酒精综合征”（fetal alcohol spectrum disorders,FASD）。小鼠通常作为研究该病的动物模型。该实验采用体外培养技术及体内冲胚法研究雌鼠怀孕前后酒精摄入对各期植入前胚胎全基因组DNAT基化模式建立的影响。小鼠植入前胚胎体外培养实验发现,体外实验组I（怀孕前酒精处理组1,除8-cell外,其他各期胚胎的DNA甲基化水平明显低于体外对照组;体外实验组II（正常胚胎在含乙醇的培养基中培养）,各期植入前胚胎DNA甲基化水平均明显低于体外对照组。体内实验发现,体内实验组I（怀孕前酒精处理组）与体内的实验组II（怀孕后酒精处理组）,各期植入前胚胎DNA甲基化水平明显低于体内对照组。体内、外实验结果表明：受精前后酒精对各期植入前胚胎DNA甲基化模式的正确建立造成紊乱,该结果可为进一步揭示FSAD发病机制提供一定的实验基础。     

Does dehydration contribute to retarded fetal growth in rats exposed to alcohol during gestation?

An earlier study showed that pregnant rats given ethanol in drinking water exhibited a significant degree of dehydration. The objective of the present study was to determine whether dehydration alone contributes to fetal growth retardation in alcohol treated rats. Female Sprague-Dawley rats were divided into 4 dietary groups. Group 1 (alcohol) received 20% ethanol in drinking water for four weeks prior to mating and 30% alcohol in drinking water throughout pregnancy and a stock diet $\text{ad libitum}$. Group 2 (pair-fed) was given an amount of food equal to that consumed by the alcohol group with the alcohol isocalorically substituted by corn starch. Water was available $\text{ad libitum}$. Group 3 (pair-water) was given an amount of food and water equal to that consumed by the alcohol animals. Group 4 ($\text{ad libitum}$) was given food and water $\text{ad libitum}$. On day 21 of gestation body weights of the alcohol exposed fetuses were significantly lower than those of the other three treatment groups. The difference in fetal body weights between the pair-fed and pair-water groups was not significant. Placentas were significantly heavier in the alcohol group than in the pair-fed and pair-water groups. Maternal plasma osmolality was significantly higher in the alcohol treated rats when compared to the pair-fed and $\text{ad libitum}$ controls but not the pair-water group. No significant differences were seen in fetal plasma osmolality among the four treatment groups. It is concluded that dehydration does not contribute significantly to retarded fetal growth in rats given alcohol in drinking water as the sole source of fluid prior to and during gestation.     

Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography

Prenatal alcohol exposure (PAE) can result in a range of anomalies including brain and behavioral dysfunctions, collectively termed fetal alcohol spectrum disorder. PAE during the 1st and 2nd trimester is common, and research in animal models has documented significant neural developmental deficits associated with PAE during this period. However, little is known about the immediate effects of PAE on fetal brain vasculature. In this study, we used in utero speckle variance optical coherence tomography, a high spatial‐ and temporal‐resolution imaging modality, to evaluate dynamic changes in microvasculature of the 2nd trimester equivalent murine fetal brain, minutes after binge‐like maternal alcohol exposure. Acute binge‐like PAE resulted in a rapid (<1 hour) and significant decrease (P < .001) in vessel diameter as compared to the sham group. The data show that a single binge‐like maternal alcohol exposure resulted in swift vasoconstriction in fetal brain vessels during the critical period of neurogenesis.