Developmental origins of mechanical homeostasis in the aorta

AbstractLiving soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.

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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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