Transplacental exposure to carcinogens and risks to children: evidence from biomarker studies and the utility of omic profiling

Botsivali, Maria; Kyrtopoulos, Soterios A.

doi:10.1007/s00204-019-02428-3

Cited by 4 publications

(5 citation statements)

References 186 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Resultsmentioning

confidence: 99%

“…Smoking affects placental steroidogenesis, and in one study, the placentas of smoking mothers were shown to contain approximately half the amount of progesterone compared to the placentas of non-smoking mothers [ 122 , 123 ]. Cytochrome P450 monooxygenase CYP1A1 induction by maternal cigarette smoking or drug abuse has been convincingly demonstrated in several studies [ 122 , 123 ]. Notably, glutathione-S-transferase (GST) does not appear to be considerably increased due to maternal cigarette smoking [ 101 , 102 , 103 , 121 , 122 ], whereas UDP-glucuronosyltransferase (UGT) activity is stimulated by both cigarette smoking and alcohol intake [ 124 , 125 ].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier

Kotta-Loizou,

Pritsa,

Antasouras

et al. 2024

Diseases

View full text Add to dashboard Cite

Background: The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism. Methods: A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included. Results: During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects. Conclusions: Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier

Kotta-Loizou,

Pritsa,

Antasouras

et al. 2024

Diseases

View full text Add to dashboard Cite

show abstract

“…As such, maternal tobacco smoke (MTS) is the leading preventable cause of abnormal pregnancy outcomes (48). MTS increases the likelihood of the newborn to suffer from various NCDs in childhood and adulthood (6,45,54,62). The biological mechanism driving this is yet to be elucidated however hormones, epigenetics, oxidative stress, and DNA mutations have all been postulated.…”

Section: Sex-specific Effects Of In Utero and Adult Tobacco Smoke Expmentioning

confidence: 99%

“…Sexual dimorphism in disease susceptibility due to tobacco smoke exposure extends beyond the respiratory system, having multi-organ disease influences. Childhood cancers such as leukemia, childhood brain tumors (CBT), and lymphomas report higher incidence in boys than girls (6). Adult female smokers have a greater rate of cancer, despite lower smoking intensity than males (3).…”

Section: Multi-organ Effectsmentioning

confidence: 99%

Sex-specific effects of in utero and adult tobacco smoke exposure

Reddy

Oliver

2021

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Tobacco smoke has harmful effects on a multi-organ level. Exposure to smoke, whether in utero or environmental, significantly increases susceptibility. This susceptibility has been identified to be divergent between males and females. However, there remains a distinct lack of thorough research into the relationship between sex and exposure to tobacco. Females tend to generate a more significant response than males during adulthood exposure. The intrauterine environment is meticulously controlled, and exposure to tobacco presents a significant factor that contributes to poor health outcomes and susceptibility later in life. Analysis of these effects in relation to the sex of the offspring is yet to be holistically reviewed and summarised. In this review, we will delineate the time-dependent relationship between tobacco smoke exposure and sex-specific disease susceptibility. We further outline possible biological mechanisms that may contribute to the identified pattern.

show abstract

“…The current analysis further evaluates the chemicals reported by OEHHA as having sufficient animal data to calculate TP, PN, and adult potency and compares these potency estimates across life stages for case study chemicals. Note that the term "transplacental" is meant to indicate carcinogenesis due to chemicals crossing the placenta and damaging fetal tissues, either as parent or metabolite, as evidenced for a wide range of carcinogens (Botsivali and Kyrtopoulos 2019), rather than as a result of effects on the maternal system or the placenta itself.…”

Section: Introductionmentioning

confidence: 99%

Comparison of carcinogenic potency across life stages: implications for the assessment of transplacental cancer risk

Dzubow

Fields

Ginsberg

et al. 2019

Journal of Toxicology and Environmental Health, Part A

View full text Add to dashboard Cite

Cancer development from in utero exposure has been documented for a variety of agents with the most commonly studied compounds exhibiting mutagenic and genotoxic carcinogen properties. Age-dependent adjustment factors (ADAFs) are applied by the US Environmental Protection Agency to many such carcinogens when assessing cancer risk from early postnatal (PN) exposures; however, this approach has not been widely considered for transplacental (TP) exposure. To explore this question and further evaluate prenatal susceptibility a database of early life animal studies developed by California Office of Environmental Health Hazard Assessment (OEHHA) enhanced with additional literature searching was evaluated. Nine genotoxic carcinogens and one mixture (cigarette smoke) have data available via TP only, PN only and adultonly protocols. Potency comparisons across these lifestages displayed similarly greater potency in male liver and brain compared to adult-only exposure. Both TP and PN exposures were not markedly different than adult-only for other targets such as female liver and blood-borne tumors. Similarity in TP and PN targets and potency for carcinogen action suggests that a 10-fold ADAF may be applied for TP exposure as is currently applied to PN exposure. A similar conclusion was reached by OEHHA. The implications of this heightened TP vulnerability are greatest for lessthan-lifetime exposure and this approach might be used to assess the level of cancer risk from exposures during pregnancy. A case example employing a mutagenic flame retardant was used to exemplify application of a TP ADAF for evaluating risks during pregnancy.

show abstract

Transplacental exposure to carcinogens and risks to children: evidence from biomarker studies and the utility of omic profiling

Cited by 4 publications

References 186 publications

Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier

Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier

Sex-specific effects of in utero and adult tobacco smoke exposure

Comparison of carcinogenic potency across life stages: implications for the assessment of transplacental cancer risk

Contact Info

Product

Resources

About