Intrauterine Programming of Physiological Systems: Causes and Consequences

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Intrauterine Programming of Physiological
Systems Causes and Consequences

• Abigail L. Fowden, Dino A. Giussani, and Alison
  J. Forhead
• Presented by Allison Baynard

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Contents

• What is Intrauterine Programming?
• Suboptimal Conditions in utero
• Review of the trimesters
• Diseases related to IU Programming
• Major causes of IU Programming (Nutrition,
  oxygenation, hormonal)
• Mechanisms for IU Programming (Genes, cells,
  tissues/organs, systems)
• Consequences

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Intrauterine Programming

• The process by which early insults at critical
  stages of development lead to permanent changes
  in tissue structure and function

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General Idea

• Relationships have been discovered between
  suboptimal intrauterine conditions for the fetus
  and the different physiological system
  functioning of the body ex-utero
• Adult disease originates in utero

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Suboptimal conditions

• Placental insufficiency
• Drug use/Alcohol
• Poor nutrition in mother
• Infection
• Radiation
• Medications
• Maternal stress

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Trimesters

• 1st- Major organs begin to form this ironically
  is most critical time in pregnancy and many dont
  know theyre pregnant
• 2nd- Fetus starts to move lungs prepare for life
  outside the uterus
• 3rd- Baby doubles weight rapidly and is ready for
  birth by the end

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Diseases associated with poor intrauterine
conditions

• CV system- hypertension, coronary heart disease,
  stroke, atherosclerosis, pre-eclampsia,
  coagulation disorders
• Metabolic- impaired glucose tolerance, insulin
  resistance, dyslipidemia, obesity, type 2
  diabetes
• Reproductive- polycystic ovary syndrome, early
  menarche, early menopause

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Diseases associated with poor intrauterine
conditions continued

• Respiratory- COPD, asthma
• Endocrine- hypercortisolism, hypothyroidism
• Nervous- neurological disorders, schizophrenia,
  dementia
• Skeletal- osteoporosis

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Major Causes of Intrauterine Programming

• Poor nutrition
• Poor oxygenation
• Hormones

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Nutritional Programming

• Subjects laboratory and farm animals
• What they did reduce fetal availability of
  macronutrients by reducing calories, reducing
  proteins, placental restriction, and reduce
  uterine blood flow
• What happened all procedures caused CV,
  metabolic, and endocrine dysfunction before and
  after birth
• What they found out they could counteract some
  dysfunction or further alter it through
  manipulation of micronutrients

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Oxygenation programming

• Subjects chick embryos
• What they did alter O2 without altering maternal
  nutrition
• What they found out hypoxia alone during early
  development can program the CV system, including
  blood vessels

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Endocrine programming

• What they found out poor conditions lower
  anabolic hormone levels and increase catabolic
  hormone level in fetus
• Directly and Indirectly alters delivery, uptake,
  and metabolic fate of nutrients used in tissues
• Glucocorticoids- overexposure hypertension,
  glucose intolerance, HPA function abnormalities

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Mechanisms of Intrauterine Programming

• Genes
• Cells
• Tissues and Organs
• Systems

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Gene Programming

• DNA can be modified by DNA methylation during
  fetal development which can alter gene expression
  (epigenetic modification)
• 2 main periods of epigenetic modification
• Gametogenesis
• Early embryogenesis

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Cell Programming

• Altered intrauterine conditions cause
• Altered protein synthesis
• Permanent changes in protein abundance
• Changes to insulin signaling pathways
• Changes to adenylyl cyclase pathways
• Altered cell physiology causes most damage during
  late gestation when cells differentiate to
  prepare for life outside of uterus

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Tissues and Organ Programming

• Changes at the cellular level cause overall
  tissue and organ changes
• The severity of change depends on timing (i.e. if
  changes occur at time of organogenesis)
• Early insult may last throughout gestation and
  cause problems throughout (placental changespoor
  nutrition and oxygenation)

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Systemic Programming

• Nature and duration of insult plays major role in
  the outcome
• Most consequences of insult present in later part
  of life as compensatory mechanisms fail

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Consequences of Intrauterine Programming

• Mutagenesis vs. physiological adaptations
• Physiological changes caused by poor intrauterine
  conditions can be passed from one generation to
  the next