Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring

Levin, Edward D.; Hawkey, Andrew; Hall, Brandon J.; Cauley, Marty; Slade, Susan; Yazdani, Elisa; Kenou, Bruny; White, Hannah; Wells, Corinne; Rezvani, Amir H.; Murphy, Susan K.

doi:10.1016/j.ntt.2019.04.003

Cited by 65 publications

(47 citation statements)

References 19 publications

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“…Altered social interactions and increased anxiety-like behaviors have also been reported (Trezza et al, 2008;Trezza et al, 2012). Recent research on paternal exposure prior to mating has been associated with impaired attentional processing and abnormal activity levels in offspring (Levin et al, 2019). This finding highlights the important contribution of the sire to developmental outcomes in offspring.…”

Section: Messages From Research With Animal Modelsmentioning

confidence: 82%

Update on the developmental consequences of cannabis use during pregnancy and lactation

Grant

Conover

Chambers

2020

Birth Defects Research

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There is a strong increase in prevalence trends for cannabis use during pregnancy and lactation as more states legalize use of this drug. Information on the teratogenic risk of cannabis is limited but some important themes can be gleaned. Studies have not found a unique phenotypic signature of prenatal exposure but an increased risk of congenital anomalies, particularly gastroschisis, has been reported. Changes in fetal growth have been described in some epidemiological studies but long‐term patterns of physical growth appear unaffected. Prenatal exposure to cannabis is not generally associated with reductions in global IQ but specific cognitive skills, especially attention and memory, can be negatively impacted. Long‐term impacts on psychological health include increased rates of depressive symptoms and anxiety as well as delinquency. Relatively little is known about the risk of maternal cannabis use during lactation but data suggest that infant exposure is relatively low compared to maternal exposure. As delta‐9‐tetrahydrocannabinol (THC) levels increase to meet consumer demand and routes of exposure diversify, there is a strong need for prospective birth‐cohort studies that collect biological samples to quantify exposure. Data from such studies will be critical to overcoming the weaknesses of past cannabis research and are essential to establishing reliable information on the risks of maternal use. Until that time, health care providers should be encouraged to talk about the risks and benefits associated with cannabis use during pregnancy and lactation with their patients, emphasizing that fetal and neonatal risks cannot be excluded at this time.

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Section: Messages From Research With Animal Modelsmentioning

confidence: 82%

Update on the developmental consequences of cannabis use during pregnancy and lactation

Grant

Conover

Chambers

2020

Birth Defects Research

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“…Offspring of adult THC‐exposed sires did not differ from control‐sired offspring on litter size, sex ratio, or body weights when measured at birth and weaning. (Levin et al, 2019).…”

Section: Cannabinoidsmentioning

confidence: 99%

“…Adolescent paternal exposure to the synthetic cannabinoid receptor agonist WIN55,212‐2 (WIN) did not alter locomotor activity in adult SD offspring at baseline or after unpredictable stress (Ibn Lahmar Andaloussi et al, 2019). Adult THC‐sired offspring showed more rapid habituation of locomotor activity relative to control‐sired offspring; this effect was not seen in adolescent offspring (Levin et al, 2019). Additionally, episodic memory was unchanged in WIN‐sired offspring relative to control offspring as measured by the object recognition test (Ibn Lahmar Andaloussi et al, 2019).…”

Section: Cannabinoidsmentioning

confidence: 99%

“…Additionally, episodic memory was unchanged in WIN‐sired offspring relative to control offspring as measured by the object recognition test (Ibn Lahmar Andaloussi et al, 2019). No effect of adolescent paternal THC exposure was seen on the novel object recognition test of non‐spatial memory (Levin et al, 2019). Although, THC‐sired offspring do not show deficits on the 16‐arm radial maze test of spatial memory, these offspring have impairments in sustained attention relative to control‐sired offspring (Levin et al, 2019).…”

Section: Cannabinoidsmentioning

confidence: 99%

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Who's your daddy? Behavioral and epigenetic consequences of paternal drug exposure

Nieto

Kosten

2019

Intl J of Devlp Neuroscience

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Substance use disorders (SUDs) reflect genetic and environmental factors. While identifying reliable genetic variants that predispose individuals to developing SUDs has been challenging, epigenetic factors may also contribute to the heritability of SUDs. Familial drug use associates with a wide range of problems in children, including an increased risk for developing a SUD. The implications of maternal drug use on offspring development are a well‐studied area; however, paternal drug use prior to conception has received relatively little attention. Paternal exposure to several environmental stimuli (i.e. stress or diet manipulations) results in behavioral and epigenetic changes in offspring. The purpose of this review is to determine the state of the preclinical literature on the behavioral and epigenetic consequences of paternal drug exposure. Drug‐sired offspring show several developmental and physiological abnormalities. These offspring also show deficits in cognitive and emotional domains. Examining sensitivity to drugs in offspring is a growing area of research. Drug‐sired offspring are resistant to the rewarding and reinforcing properties of drugs. However, greater paternal motivation for the drug, combined with high drug intake, can result in addiction‐like behaviors in offspring. Drug‐sired offspring also show altered histone modifications and DNA methylation levels of imprinted genes and microRNAs; epigenetic‐mediated changes were also noted in genes related to glutamatergic and neurotrophic factor signaling. In some instances, drug use resulted in aberrant epigenetic modifications in sire sperm, and these changes were maintained in the brains of offspring. Thus, paternal drug exposure has long‐lasting consequences that include altered drug sensitivity in subsequent generations. We discuss factors (i.e. maternal behaviors) that may moderate these paternal drug‐induced effects as well as ideas for future directions.

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“…In addition, epigenetic stressors including endocrine-disrupting chemicals, alcohol and nicotine abuse, can cause intergenerational reproductive health and metabolism effects [95][96][97][98][99][100]. In the context of endocrine-disrupting chemicals, transgenerational effects on brain, behavior, and reproduction have been documented [95,[101][102][103].…”

Section: Future Perspectivesmentioning

confidence: 99%

Genes and Diet in the Prevention of Chronic Diseases in Future Generations

Franzago

Santurbano²,

Vitacolonna

et al. 2020

IJMS

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Nutrition is a modifiable key factor that is able to interact with both the genome and epigenome to influence human health and fertility. In particular, specific genetic variants can influence the response to dietary components and nutrient requirements, and conversely, the diet itself is able to modulate gene expression. In this context and the era of precision medicine, nutrigenetic and nutrigenomic studies offer significant opportunities to improve the prevention of metabolic disturbances, such as Type 2 diabetes, gestational diabetes, hypertension, and cardiovascular diseases, even with transgenerational effects. The present review takes into account the interactions between diet, genes and human health, and provides an overview of the role of nutrigenetics, nutrigenomics and epigenetics in the prevention of non-communicable diseases. Moreover, we focus our attention on the mechanism of intergenerational or transgenerational transmission of the susceptibility to metabolic disturbances, and underline that the reversibility of epigenetic modifications through dietary intervention could counteract perturbations induced by lifestyle and environmental factors.

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Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring

Cited by 65 publications

References 19 publications

Update on the developmental consequences of cannabis use during pregnancy and lactation

Update on the developmental consequences of cannabis use during pregnancy and lactation

Who's your daddy? Behavioral and epigenetic consequences of paternal drug exposure

Genes and Diet in the Prevention of Chronic Diseases in Future Generations

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