Perinatal TCDD exposure and the adult onset of autoimmune disease

Gogal, Robert M.; Holladay, Steven D.

doi:10.1080/10408360802483201

Cited by 25 publications

(11 citation statements)

References 43 publications

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“…Age at menarche may be a marker for non-estrogen-mediated effects on the immune system, e.g., perinatal factors (43, 44), early life infections (45) and social hardship (46). xenobiotics, infections and stress may impact immune development (47) and evidence is growing for a role of early life factors in autoimmune diseases (48–50). Together, these findings support further study of early life factors and autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women

Parks

Miller²,

Satoh

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Autoantibodies are of growing interest in cancer research as potential biomarkers; yet the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population, and are more prevalent in women and older adults. Here we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women. Methods We analyzed data on reproductive history and exogenous hormone use in relation to serum ANA in 2,037 females ages 12 and older from the National Health and Nutrition Examination Survey (NHANES; 1999–2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were adjusted for age, race and poverty-income-ratio, and models were stratified by menopause status. Results In premenopausal women ages 20 and older, ANA prevalence was associated with parity (p<0.001; parous versus nulliparous POR=2.0; 95%CI 1.2, 3.4), but in parous women ANA did not vary by number of births, age at first birth, years since last birth or breastfeeding. In postmenopausal women, ANA prevalence was associated with an older age at menarche (p=0.019; age 16–20 versus 10–12 years POR=3.0, 95%CI 1.6, 5.9), but not with parity. Oral contraceptives and estrogen therapy were not associated with a higher ANA prevalence. Conclusions Childbearing (having had one or more births) may explain age-associated elevations in ANA prevalence seen in premenopausal women. Impact These findings highlight the importance of considering reproductive history in studies of autoimmunity and cancer in women.

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Section: Discussionmentioning

confidence: 99%

Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women

Parks

Miller²,

Satoh

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…However, interestingly, paradoxical conclusions could be found when we reviewed the previous studies. For example, results determining whether the AhR is essential for the development of a functional immune system or whether the activation or suppression of AhR leads to profound immunosuppression, were not consistent [2,6,9,10,11,12]. Such functional diversity might depend on development stage, the diversity of ligand type or structure, the cell or tissue types involved, the microenvironment of the study system, and also the dose level.…”

Section: Introductionmentioning

confidence: 99%

The Role of AhR in Autoimmune Regulation and Its Potential as a Therapeutic Target against CD4 T Cell Mediated Inflammatory Disorder

Zhu

Xie

Zhao

2014

IJMS

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AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently.

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“…It has been shown that intrauterine exposure to dioxin leads to the development of autoimmunity in animals (18). Since most of the developmental activity in the immune system occurs in the first trimester of pregnancy, exposure to foreign substances during this period may have a greater impact.…”

Section: Introductionmentioning

confidence: 99%

Fetal and Neonatal Endocrine Disruptors

Ünüvar¹,

Büyükgebiz²

2012

JCRPE

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Endocrine disruptors are substances commonly encountered in every setting and condition in the modern world. It is virtually impossible to avoid the contact with these chemical compounds in our daily life. Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products. Natural chemicals found in human and animal food (phytoestrogens) also act as endocrine disruptors. Different from adults, children are not exposed only to chemical toxins in the environment but may also be exposed during their intrauterine life. Hundreds of toxic substances, which include neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development, may affect the fetus via the placental cord and these substances may be excreted in the meconium. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways are immature, especially in the first months of life. The ability of the newborn to metabolize, detoxify and eliminate many toxins is different from that of the adults. Although exposures occur during fetal or neonatal period, their effects may sometimes be observed in later years. Further studies are needed to clarify the effects of these substances on the endocrine system and to provide evidence for preventive measures.Conflict of interest:None declared.

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Perinatal TCDD exposure and the adult onset of autoimmune disease

Cited by 25 publications

References 43 publications

Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women

Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women

The Role of AhR in Autoimmune Regulation and Its Potential as a Therapeutic Target against CD4 T Cell Mediated Inflammatory Disorder

Fetal and Neonatal Endocrine Disruptors

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