Paternal exposure to cigarette smoke condensate leads to reproductive sequelae and developmental abnormalities in the offspring of mice

Esakky, Prabagaran; Hansen, Deborah A.; Drury, Andrea; Felder, Paul; Cusumano, Andrew; Moley, Kelle H.

doi:10.1016/j.reprotox.2016.08.017

Cited by 15 publications

(10 citation statements)

References 61 publications

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“…We found that females that mated with males exposed neonatally to CSC had increased resorptions, perhaps owing to implantation failure of poor-quality embryos. This finding is consistent with our earlier report that adult male exposure to CSC led to phenotypic changes and developmental defects in the offspring (10). In a rat model, paternal exposure to CS-impaired blastocyst implantation and embryonic development (50).…”

Section: Discussionsupporting

confidence: 93%

“…To model exposure to CS, we have used in vivo mouse models in which mice are injected with cigarette smoke condensate (CSC) and in vitro models in which a spermatocyte cell line is cultured with CSC. We have demonstrated that CSC causes several molecular changes in the testis, reduces sperm motility and male fertility, and results in embryonic malformation in the offspring of exposed males (9,10). Similar studies have also shown that chronic exposure to CS in rodents blocks spermatogenesis (11) and increases the rate of spermatogonial stem-cell mutations (12).…”

mentioning

confidence: 61%

“…Ex vivo CSC exposure and assessment of cotinine and testosterone cotinine measurement, ;250 ml of medium was collected on P11.5 and processed with the cotinine solid-phase competitive ELISA Detection Kit (Abnova, Taoyuan City, Taiwan) as per the manufacturer's specifications and our protocol (10). The concentration of cotinine in the collected medium samples was estimated from the cotinine standards, and at least 3 replicates were used for the assay.…”

Section: Detection Of Dna Damage By Tunel Assaymentioning

confidence: 99%

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Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo

Esakky

Hansen²,

Drury

et al. 2017

FASEB j.

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Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an testicular explant model and exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar and Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate and .

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 61%

Section: Detection Of Dna Damage By Tunel Assaymentioning

confidence: 99%

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Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo

Esakky

Hansen²,

Drury

et al. 2017

FASEB j.

Self Cite

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“…Cigarette smoking results in accumulation of benzo(a)pyrene (B[a]P) and cotinine, ultimately leading to DNA damage and testicular cytotoxicity in rodent models. In a recent study, Esakky and colleagues [ 39 ] reported significantly decreased expression of aryl hydrocarbon receptor ( Ahr ), and enhanced expression of Fas, FasL, BCL2, and activated caspase-3 proteins in testes exposed to cigarette smoke condensate. The reduced expression of Ahr increases susceptibility of germ cells to polycyclic aromatic hydrocarbons, while the remaining proteins all induce apoptosis via extrinsic (FAS, FASL) or mitochondrial processes (BCL, caspase-3).…”

Section: Introductionmentioning

confidence: 99%

Smoke, alcohol and drug addiction and male fertility

Sansone

Dato

Angelis

et al. 2018

Reprod Biol Endocrinol

197

113

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In recent decades, the decline in human fertility has become increasingly more worrying: while therapeutic interventions might help, they are vexing for the couple and often burdened with high failure rates and costs. Prevention is the most successful approach to fertility disorders in males and females alike. We performed a literature review on three of the most common unhealthy habits – tobacco, alcohol and drug addiction – and their reported effects on male fertility. Tobacco smoking is remarkably common in most first-world countries; despite a progressive decline in the US, recent reports suggest a prevalence of more than 30% in subjects of reproductive age – a disturbing perspective, given the well-known ill-effects on reproductive and sexual function as well as general health. Alcohol consumption is often considered socially acceptable, but its negative effects on gonadal function have been consistently reported in the last 30 years. Several studies have reported a variety of negative effects on male fertility following drug abuse – a worrying phenomenon, as illicit drug consumption is on the rise, most notably in younger subjects. While evidence in these regards is still far from solid, mostly as a result of several confounding factors, it is safe to assume that cessation of tobacco smoking, alcohol consumption and recreational drug addiction might represent the best course of action for any couple trying to achieve pregnancy.

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“…1 In particular, preconception male exposures to a range of environmental factors induce alterations to the developmental program of sperm, which can be correlated with increased rates of structural and metabolic defects in the next generation. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] These studies challenge the singular importance of maternal in utero environmental exposures and implicate paternal exposure history as an additional and important mediator of both environmentally-induced disease and dysgenesis. 17,18 However, the capacity of preconception paternal exposures to broadly contribute to the development of environmentally-induced disease has not been rigorously explored, largely due to the common misconception that sperm do not transmit heritable information beyond the genetic code.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation-independent growth restriction and altered developmental programming in a mouse model of preconception male alcohol exposure

et al. 2017

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The preconception environment is a significant modifier of dysgenesis and the development of environmentally-induced disease. To date, fetal alcohol spectrum disorders (FASDs) have been exclusively associated with maternal exposures, yet emerging evidence suggests male-inherited alterations in the developmental program of sperm may be relevant to the growth-restriction phenotypes of this condition. Using a mouse model of voluntary consumption, we find chronic preconception male ethanol exposure associates with fetal growth restriction, decreased placental efficiency, abnormalities in cholesterol trafficking, sex-specific alterations in the genetic pathways regulating hepatic fibrosis, and disruptions in the regulation of imprinted genes. Alterations in the DNA methylation profiles of imprinted loci have been identified in clinical studies of alcoholic sperm, suggesting the legacy of paternal drinking may transmit via heritable disruptions in the regulation of imprinted genes. However, the capacity of sperm-inherited changes in DNA methylation to broadly transmit environmentally-induced phenotypes remains unconfirmed. Using bisulphite mutagenesis and second-generation deep sequencing, we find no evidence to suggest that these phenotypes or any of the associated transcriptional changes are linked to alterations in the sperm-inherited DNA methylation profile. These observations are consistent with recent studies examining the male transmission of diet-induced phenotypes and emphasize the importance of epigenetic mechanisms of paternal inheritance beyond DNA methylation. This study challenges the singular importance of maternal alcohol exposures and suggests paternal alcohol abuse is a significant, yet overlooked epidemiological factor complicit in the genesis of alcohol-induced growth defects, and may provide mechanistic insight into the failure of FASD children to thrive postnatally.

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Paternal exposure to cigarette smoke condensate leads to reproductive sequelae and developmental abnormalities in the offspring of mice

Cited by 15 publications

References 61 publications

Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo

Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo

Smoke, alcohol and drug addiction and male fertility

DNA methylation-independent growth restriction and altered developmental programming in a mouse model of preconception male alcohol exposure

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