Detecting Neurodevelopmental Effects of Early-Gestation Ethanol Exposure: A Nonhuman Primate Model of Ethanol Drinking During Pregnancy.
Animals
Blood Alcohol Content
Case-Control Studies
Disease Models, Animal
Estradiol
/ blood
Ethanol
/ adverse effects
Female
Fetal Development
/ drug effects
Macaca mulatta
Menstrual Cycle
/ drug effects
Pregnancy
Pregnancy Trimester, First
/ drug effects
Prenatal Exposure Delayed Effects
/ chemically induced
Progesterone
/ blood
EtOH Self-Administration
Fetal Alcohol Spectrum Disorder
In Vivo Fetal Imaging
Rhesus Macaque
Journal
Alcoholism, clinical and experimental research
ISSN: 1530-0277
Titre abrégé: Alcohol Clin Exp Res
Pays: England
ID NLM: 7707242
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
21
10
2018
accepted:
07
12
2018
pubmed:
15
12
2018
medline:
21
3
2020
entrez:
15
12
2018
Statut:
ppublish
Résumé
Gestational ethanol (EtOH) exposure is associated with multiple developmental abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). While the majority of women abstain from EtOH following knowledge of pregnancy, one contributing factor to the high FASD prevalence is that pregnancy is not detected until 4 to 6 weeks. Thus, EtOH consumption continues during the initial stages of fetal development. An experimental protocol is described in which rhesus macaques self-administer 1.5 g/kg/d EtOH (or isocaloric maltose dextrin) prior to pregnancy and through the first 60 days of a 168-day gestation term. Menstrual cycles were monitored, including measurements of circulating estradiol and progesterone levels. The latency to consume 1.5 g/kg EtOH and blood EtOH concentration (BEC) was measured. Twenty-eight fetuses (14 EtOH and 14 controls) were generated in this study. EtOH did not affect menstrual cycles or the probability of successful breeding. No EtOH-induced gross adverse effects on pregnancy were observed. Individual variability in latency to complete drinking translated into variability in BEC, measured 90 minutes following session start. Drinking latencies in controls and EtOH drinkers were longer in the second gestational month than in the first. All pregnancies reached the planned experimental time point of G85, G110, or G135, when in utero MRIs were performed, fetuses were delivered by caesarean section, and brains were evaluated with ex vivo procedures, including slice electrophysiology. Fetal tissues have been deposited to the Monkey Alcohol Tissue Research Resource. This FASD model takes advantage of the similarities between humans and rhesus macaques in gestational length relative to brain development, as well as similarities in EtOH self-administration and metabolism. The daily 1.5 g/kg dose of EtOH through the first trimester does not influence pregnancy success rates. However, pregnancy influences drinking behavior during the second month of pregnancy. Future publications using this model will describe the effect of early-gestation EtOH exposure on anatomical and functional brain development at subsequent gestational ages.
Sections du résumé
BACKGROUND
Gestational ethanol (EtOH) exposure is associated with multiple developmental abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). While the majority of women abstain from EtOH following knowledge of pregnancy, one contributing factor to the high FASD prevalence is that pregnancy is not detected until 4 to 6 weeks. Thus, EtOH consumption continues during the initial stages of fetal development.
METHODS
An experimental protocol is described in which rhesus macaques self-administer 1.5 g/kg/d EtOH (or isocaloric maltose dextrin) prior to pregnancy and through the first 60 days of a 168-day gestation term. Menstrual cycles were monitored, including measurements of circulating estradiol and progesterone levels. The latency to consume 1.5 g/kg EtOH and blood EtOH concentration (BEC) was measured.
RESULTS
Twenty-eight fetuses (14 EtOH and 14 controls) were generated in this study. EtOH did not affect menstrual cycles or the probability of successful breeding. No EtOH-induced gross adverse effects on pregnancy were observed. Individual variability in latency to complete drinking translated into variability in BEC, measured 90 minutes following session start. Drinking latencies in controls and EtOH drinkers were longer in the second gestational month than in the first. All pregnancies reached the planned experimental time point of G85, G110, or G135, when in utero MRIs were performed, fetuses were delivered by caesarean section, and brains were evaluated with ex vivo procedures, including slice electrophysiology. Fetal tissues have been deposited to the Monkey Alcohol Tissue Research Resource.
CONCLUSIONS
This FASD model takes advantage of the similarities between humans and rhesus macaques in gestational length relative to brain development, as well as similarities in EtOH self-administration and metabolism. The daily 1.5 g/kg dose of EtOH through the first trimester does not influence pregnancy success rates. However, pregnancy influences drinking behavior during the second month of pregnancy. Future publications using this model will describe the effect of early-gestation EtOH exposure on anatomical and functional brain development at subsequent gestational ages.
Identifiants
pubmed: 30549282
doi: 10.1111/acer.13938
pmc: PMC6370522
mid: NIHMS1002048
doi:
Substances chimiques
Blood Alcohol Content
0
Ethanol
3K9958V90M
Progesterone
4G7DS2Q64Y
Estradiol
4TI98Z838E
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
250-261Subventions
Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA007468
Pays : United States
Organisme : NIAAA NIH HHS
ID : R24 AA019431
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA024757
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA010760
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA021981
Pays : United States
Informations de copyright
© 2018 by the Research Society on Alcoholism.
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