Developmental Origins of Health and Disease: Integrating Environmental Influences

Abstract There are now robust data supporting the Developmental Origins of Health and Disease (DOHaD) paradigm. This includes human and animal data focusing on nutrition or environmental chemicals during development. However, the term DOHaD has not been generally accepted as the official term to be used when one is concerned with understanding the pathophysiological basis for how environmental influences acting during early development influence the risk of later noncommunicable diseases. Similarly, there is no global research or public health program built around the DOHaD paradigm that encompasses all aspects of environment. To better inform the global health efforts aimed at addressing the growing epidemic of chronic noncommunicable diseases of environmental origin, we propose a two-pronged approach: first, to make it clear that the current concept of DOHaD comprehensively includes a range of environmental factors and their relevance to disease occurrence not just throughout the life span but potentially across several generations; and second, to initiate the discussion of how adoption of DOHaD can promote a more realistic, accurate, and integrative approach to understanding environmental disruption of developmental programming and better inform clinical and policy interventions. (Endocrinology 156: 3416–3421, 2015)

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Role of exposure to environmental chemicals in developmental origins of health and disease

Developmental Origins of Health and Disease ◽

10.1017/cbo9780511544699.008 ◽

2009 ◽

pp. 82-97 ◽

Cited By ~ 1

Author(s):

Jerrold J. Heindel ◽

Cindy Lawler

Keyword(s):

Environmental Chemicals ◽

Developmental Origins ◽

Health And Disease

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Homage to the ‘H’ in developmental origins of health and disease

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174416000465 ◽

2016 ◽

Vol 8 (1) ◽

pp. 8-29 ◽

Cited By ~ 12

Author(s):

C. S. Rosenfeld

Keyword(s):

Female Offspring ◽

Postnatal Period ◽

Environmental Chemicals ◽

Primary Concern ◽

Developmental Origins ◽

Adult Health ◽

Fetal Origins ◽

Adult Disease ◽

Remediation Strategies ◽

Health And Disease

Abundant evidence exists linking maternal and paternal environments from pericopconception through the postnatal period to later risk to offspring diseases. This concept was first articulated by the late Sir David Barker and as such coined the Barker Hypothesis. The term was then mutated to Fetal Origins of Adult Disease and finally broadened to developmental origins of adult health and disease (DOHaD) in recognition that the perinatal environment can shape both health and disease in resulting offspring. Developmental exposure to various factors, including stress, obesity, caloric-rich diets and environmental chemicals can lead to detrimental offspring health outcomes. However, less attention has been paid to date on measures that parents can take to promote the long-term health of their offspring. In essence, have we neglected to consider the ‘H’ in DOHaD? It is the ‘H’ component that should be of primary concern to expecting mothers and fathers and those seeking to have children. While it may not be possible to eliminate exposure to all pernicious factors, prevention/remediation strategies may tip the scale to health rather than disease. By understanding disruptive DOHaD mechanisms, it may also illuminate behavioral modifications that parents can adapt before fertilization and throughout the neonatal period to promote the lifelong health of their male and female offspring. Three possibilities will be explored in the current review: parental exercise, probiotic supplementation and breastfeeding in the case of mothers. The ‘H’ paradigm should be the focus going forward as a healthy start can indeed last a lifetime.

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Perfecting people: the inexorable rise of prevention science

Blinded by Science ◽

10.1332/policypress/9781447322337.003.0006 ◽

2017 ◽

Author(s):

David Wastell ◽

Sue White

Keyword(s):

Economic Modeling ◽

Prevention Science ◽

Evidence Based ◽

Developmental Origins ◽

Human Flourishing ◽

Fundamental Limitations ◽

Policy Interventions ◽

Early Twenty ◽

Health And Disease ◽

Late Twentieth

This chapter reviews the rise of prevention science in the late twentieth and early twenty first centuries. Located within the developmental origins of health and disease paradigm, prevention science promotes intervention to stop damage and ensure optimal human flourishing. Prevention science combines infant determinism, economic modeling and versions of evidence-based practice, with consequences for concepts of normality. Although persuasive, we illustrate the fundamental limitations and flaws of the macro-economical approach, with reference to the influential work of James Heckman. The use of biomarkers to enable more effective targeting of policy interventions is highlighted, although we note that the benefits of such approaches are marginal.

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Sex-Specific Placental Responses in Fetal Development

Endocrinology ◽

10.1210/en.2015-1227 ◽

2015 ◽

Vol 156 (10) ◽

pp. 3422-3434 ◽

Cited By ~ 165

Author(s):

Cheryl S. Rosenfeld

Keyword(s):

Environmental Changes ◽

Laboratory Mouse ◽

Environmental Chemicals ◽

Dependent Manner ◽

Developmental Origins ◽

Adult Health ◽

Extrinsic Factors ◽

Placental Function ◽

Health And Disease ◽

Critical Organ

The placenta is an ephemeral but critical organ for the survival of all eutherian mammals and marsupials. It is the primary messenger system between the mother and fetus, where communicational signals, nutrients, waste, gases, and extrinsic factors are exchanged. Although the placenta may buffer the fetus from various environmental insults, placental dysfunction might also contribute to detrimental developmental origins of adult health and disease effects. The placenta of one sex over the other might possess greater ability to respond and buffer against environmental insults. Given the potential role of the placenta in effecting the lifetime health of the offspring, it is not surprising that there has been a resurging interest in this organ, including the Human Placental Project launched by the National Institutes of Child Health and Human Development. In this review, we will compare embryological development of the laboratory mouse and human chorioallantoic placentae. Next, evidence that various species, including humans, exhibit normal sex-dependent structural and functional placental differences will be examined followed by how in utero environmental changes (nutritional state, stress, and exposure to environmental chemicals) might interact with fetal sex to affect this organ. Recent data also suggest that paternal state impacts placental function in a sex-dependent manner. The research to date linking placental maladaptive responses and later developmental origins of adult health and disease effects will be explored. Finally, we will focus on how sex chromosomes and epimutations may contribute to sex-dependent differences in placental function, the unanswered questions, and future directions that warrant further consideration.

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Animal Models for DOHaD Research: Focus on Hypertension of Developmental Origins

Biomedicines ◽

10.3390/biomedicines9060623 ◽

2021 ◽

Vol 9 (6) ◽

pp. 623

Author(s):

Chien-Ning Hsu ◽

You-Lin Tain

Keyword(s):

Animal Models ◽

Early Life ◽

Later Life ◽

Convincing Evidence ◽

Environmental Chemicals ◽

Developmental Origins ◽

Critical Window ◽

Health And Disease ◽

Underlying Mechanisms

Increasing evidence suggests that fetal programming through environmental exposure during a critical window of early life leads to long-term detrimental outcomes, by so-called developmental origins of health and disease (DOHaD). Hypertension can originate in early life. Animal models are essential for providing convincing evidence of a causal relationship between diverse early-life insults and the developmental programming of hypertension in later life. These insults include nutritional imbalances, maternal illnesses, exposure to environmental chemicals, and medication use. In addition to reviewing the various insults that contribute to hypertension of developmental origins, this review focuses on the benefits of animal models in addressing the underlying mechanisms by which early-life interventions can reprogram disease processes and prevent the development of hypertension. Our understanding of hypertension of developmental origins has been enhanced by each of these animal models, narrowing the knowledge gap between animal models and future clinical translation.

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Targeting the Renin–Angiotensin–Aldosterone System to Prevent Hypertension and Kidney Disease of Developmental Origins

International Journal of Molecular Sciences ◽

10.3390/ijms22052298 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2298

Author(s):

Chien-Ning Hsu ◽

You-Lin Tain

Keyword(s):

Kidney Disease ◽

Current Knowledge ◽

Current Evidence ◽

Developmental Origins ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Health And Disease ◽

Nitric Oxide Deficiency ◽

Developing Kidney ◽

Prevention Of Hypertension

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.

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9th World Congress on Developmental Origins of Health and Disease

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415002329 ◽

2015 ◽

Vol 6 (S2) ◽

pp. S1-S53

Keyword(s):

Developmental Origins ◽

World Congress ◽

Health And Disease

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Endocrine Disrupting Chemicals: Current Understanding, New Testing Strategies and Future Research Needs

International Journal of Molecular Sciences ◽

10.3390/ijms22020933 ◽

2021 ◽

Vol 22 (2) ◽

pp. 933

Author(s):

Maria E. Street ◽

Karine Audouze ◽

Juliette Legler ◽

Hideko Sone ◽

Paola Palanza

Keyword(s):

Endocrine Disrupting Chemicals ◽

Endocrine System ◽

Current Understanding ◽

Future Research ◽

Developmental Origins ◽

Research Needs ◽

Important Class ◽

Testing Strategies ◽

Endocrine Disrupting ◽

Health And Disease

Endocrine disrupting chemicals (EDCs) are exogenous chemicals which can disrupt any action of the endocrine system, and are an important class of substances which play a role in the Developmental Origins of Health and Disease (DOHaD) [...]

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Toxicant effects on mammalian oocyte mitochondria†

Biology of Reproduction ◽

10.1093/biolre/ioab002 ◽

2021 ◽

Author(s):

Kelli F Malott ◽

Ulrike Luderer

Keyword(s):

Assisted Reproductive Technologies ◽

Primordial Germ Cells ◽

Reproductive Technologies ◽

Mature Oocyte ◽

Developmental Origins ◽

Founder Population ◽

Mammalian Oocyte ◽

Transport Chain ◽

Polycyclic Aromatic ◽

Health And Disease

Abstract Oocyte mitochondria are unique organelles that establish a founder population in primordial germ cells (PGCs). As the oocyte matures in the postnatal mammalian ovary during folliculogenesis it increases exponentially in volume, and the oocyte mitochondria population proliferates to about 100 000 mitochondria per healthy, mature murine oocyte. The health of the mature oocyte and subsequent embryo is highly dependent on the oocyte mitochondria. Mitochondria are especially sensitive to toxic insults, as they are a major source of reactive oxygen species (ROS), they contain their own DNA (mtDNA) that is unprotected by histone proteins, they contain the electron transport chain that uses electron donors, including oxygen, to generate ATP, and they are important sensors for overall cellular stress. Here we review the effects that toxic insults including chemotherapeutics, toxic metals, plasticizers, pesticides, polycyclic aromatic hydrocarbons (PAHs), and ionizing radiation can have on oocyte mitochondria. This is very clearly a burgeoning field, as our understanding of oocyte mitochondria and metabolism is still relatively new, and we contend much more research is needed to understand the detrimental impacts of exposure to toxicants on oocyte mitochondria. Developing this field further can benefit our understanding of assisted reproductive technologies and the developmental origins of health and disease (DOHaD).

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