Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models

Bruner‐Tran, Kaylon L.; Gnecco, Juan; Ding, Tan; Glore, Dana R.; Pensabene, Virginia; Osteen, Kevin G.

doi:10.1016/j.reprotox.2016.07.007

Cited by 92 publications

(61 citation statements)

References 155 publications

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“…Several environmental agents, especially endocrine disruptors [ 64 ] and obesogens [ 65 ] have received considerable attention. An extensive list of poorly metabolized, persistent chemicals, including plasticizers, flame retardants, and insecticides, act as agonists and antagonists in receptor signaling.…”

Section: The Redox Interface In Disease Riskmentioning

confidence: 99%

Redox theory of aging: implications for health and disease

Jones

2017

Clinical Science

145

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Genetics ultimately defines an individual, yet the phenotype of an adult is extensively determined by the sequence of lifelong exposures, termed the exposome. The redox theory of aging recognizes that animals evolved within an oxygen-rich environment, which created a critical redox interface between an organism and its environment. Advances in redox biology show that redox elements are present throughout metabolic and structural systems and operate as functional networks to support the genome in adaptation to environmental resources and challenges during lifespan. These principles emphasize that physical and functional phenotypes of an adult are determined by gene–environment interactions from early life onward. The principles highlight the critical nature of cumulative exposure memories in defining changes in resilience progressively during life. Both plasma glutathione and cysteine systems become oxidized with aging, and the recent finding that cystine to glutathione ratio in human plasma predicts death in coronary artery disease (CAD) patients suggests this could provide a way to measure resilience of redox networks in aging and disease. The emerging concepts of cumulative gene–environment interactions warrant focused efforts to elucidate central mechanisms by which exposure memory governs health and etiology, onset and progression of disease.

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Section: The Redox Interface In Disease Riskmentioning

confidence: 99%

Redox theory of aging: implications for health and disease

Jones

2017

Clinical Science

145

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“…In particular, 3D culture systems and microphysiological organ‐on‐a‐chip systems enable the direct study of uterine tissue remodeling, hormone cycling, flow dynamics, cellular migration, and cell–cell interaction during the menstrual cycle and in endometriosis . Interconnected organ‐on‐a‐chip systems are also being used in combination with traditional animal models to unravel complex and multifactorial disease processes such as the mechanisms by which endocrine disrupting chemicals leads to endometrial dysregulation and disease, and the effects of ectopic endometrial tissue on the healthy endometrium . Moreover, human stem‐cell‐derived uterus epithelium with physiological responses to estrogen and progesterone could become a source for patient‐specific disease modeling and treatment development.…”

Section: Female‐specific Organs‐on‐a‐chipmentioning

confidence: 99%

Organ‐on‐a‐Chip Systems for Women's Health Applications

Nawroth

Rogal

Weiß

et al. 2017

Adv Healthcare Materials

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Biomedical research, for a long time, has paid little attention to the influence of sex in many areas of study, ranging from molecular and cellular biology to animal models and clinical studies on human subjects. Many studies solely rely on male cells/tissues/animals/humans, although there are profound differences in male and female physiology, which can significantly impact disease mechanisms, toxicity of compounds, and efficacy of pharmaceuticals. In vitro systems have been traditionally very limited in their capacity to recapitulate female-specific physiology and anatomy such as dynamic sex-hormone levels and the complex interdependencies of female reproductive tract organs. However, the advent of microphysiological organ-on-a-chip systems, which attempt to recreate the 3D structure and function of human organs, now gives researchers the opportunity to integrate cells and tissues from a variety of individuals. Moreover, adding a dynamic flow environment allows mimicking endocrine signaling during the menstrual cycle and pregnancy, as well as providing a controlled microfluidic environment for pharmacokinetic modeling. This review gives an introduction into preclinical and clinical research on women's health and discusses where organ-on-a-chip systems are already utilized or have the potential to deliver new insights and enable entirely new types of studies.

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“…shear stresses). 23 Potential applications of EndoChip are to assess pre-pubertal impacts of exposure to endocrine active chemicals on longer-term uterine health and disease. Microphysiological modeling of hormonal balance has been presented in concept for the male reproductive tract.…”

Section: Gender-based Testingmentioning

confidence: 99%

Programming microphysiological systems for children’s health protection

Knudsen

Klieforth²,

Slikker

2017

Exp Biol Med (Maywood)

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This 'commentary' summarizes research needs and opportunities for engineered MPS models for developmental and reproductive toxicity testing. Emerging concepts can be taken forward to a virtual tissue modeling framework for assessing chemical (and non-chemical) stressors on human development. These models will advance children's health research, both basic and translational and new ways to evaluate complex embryological and reproductive impacts of drug and chemical exposures to inform safety assessments. AbstractMicrophysiological systems (MPS) and computer simulation models that recapitulate the underlying biology and toxicology of critical developmental transitions are emerging tools for developmental effects assessment of drugs/chemicals. Opportunities and challenges exist for their application to alternative, more public health relevant and efficient chemical toxicity testing methods. This is especially pertinent to children's health research and the evaluation of complex embryological and reproductive impacts of drug/chemical exposure. Scaling these technologies to higher throughput is a key challenge and drives the need for in silico models for quantitative prediction of developmental toxicity to inform safety assessments. One example is cellular agent-based models, constructed from extant embryology, that produce data useful to simulate critical developmental transitions and thereby predict phenotypic consequences of disruption in silico. Biologically inspired MPS models built from human induced pluripotent stem (iPS)-derived cells and synthetic matrices that recapitulate organ-specific physiologies and native tissue architectures are providing exciting new research opportunities to advance the assessment of developmental toxicity and offer the possibility of deriving a full 'human on a chip' system, or a 'Homunculus.'

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Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models

Cited by 92 publications

References 155 publications

Redox theory of aging: implications for health and disease

Redox theory of aging: implications for health and disease

Organ‐on‐a‐Chip Systems for Women's Health Applications

Programming microphysiological systems for children’s health protection

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