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2.1 Substrates of metabolism At birth, the supply ...
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Flashcards in this deck (67)

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  • Why does the newborn depend on its fuel reserves immediately after birth?

    Because the supply of nutrients from the mother stops at birth and the infant must rely on readily mobilisable fuel reserves until adequate suckling is established.

    metabolism neonatal

  • What are the main fuel reserves for the neonate?

    • Liver glycogen
    • Muscle glycogen
    • Fat
    neonatal fuel

  • How do hepatic glycogen concentrations change around birth?

    Hepatic glycogen concentrations increase before birth, are rapidly mobilised after birth, and are depleted around 12 hours post-delivery.

    liver glycogen

  • What fuel source do infants primarily use after hepatic glycogen is depleted and before enteral feeding?

    Infants begin to break down fat until enteral feeding is established.

    neonatal fat

  • How do glycogen levels change in the weeks after birth?

    Glycogen levels slowly rise to adult levels over the next few weeks after birth.

    development glycogen

  • How does muscle glycogen change before and after birth compared to hepatic glycogen?

    Muscle glycogen increases before birth and decreases rapidly thereafter, but the post-birth decrease is less rapid than that of hepatic glycogen.

    muscle glycogen

  • Which gluconeogenic enzymes increase before birth as described in the text?

    • Glucose-6-phosphatase (G6P)
    • PEPCK
    enzymes gluconeogenesis

  • How do hepatic and renal activities of glucose-6-phosphatase at birth compare with late gestation or adult levels?

    At birth, hepatic and renal activity of glucose-6-phosphatase can reach levels higher than those found in late gestation or in adult animals.

    g6p activity

  • Which endocrine changes around birth activate gluconeogenic enzymes?

    • Increase in plasma cortisol
    • Increase in catecholamines
    • Increase in glucagon
    • Decrease in insulin
    endocrine hormones

  • In fetal sheep, what hormonal surge is required for ontogenic increases in tissue G6P and PEPCK activities?

    The prepartum cortisol surge is required for the ontogenic increments in tissue G6P and PEPCK activities.

    cortisol sheep

  • What is the effect of fetal adrenalectomy on hepatic and renal G6P and PEPCK increases close to term in sheep?

    Fetal adrenalectomy prevents the increases in hepatic and renal G6P and PEPCK seen close to term.

    sheep adrenalectomy

  • What is the effect of exogenous cortisol infusion earlier in gestation on gluconeogenic enzymes in fetal sheep?

    An exogenous infusion of cortisol earlier in gestation stimulates the increases in gluconeogenic enzymes prematurely.

    cortisol stimulation

  • How does fetal thyroidectomy (hypothyroidism) affect hepatic and renal gluconeogenic enzymes near term?

    Hypothyroidism induced by fetal thyroidectomy is associated with a reduction in hepatic and renal gluconeogenic enzymes near term.

    thyroid hypothyroidism

  • What happens to tissue G6P and PEPCK when the prepartum rise in plasma T3 is prevented by thyroidectomy in sheep?

    The increments in tissue G6P and PEPCK normally seen towards term are abolished when the prepartum rise in plasma T3 is prevented by thyroidectomy.

    sheep t3

  • What is the effect of premature elevation of plasma T3 concentration on tissue gluconeogenic enzyme activities?

    Premature elevation of plasma T3 alone causes significant increases in tissue gluconeogenic enzyme activities.

    t3 enzyme

  • What role does T3 play in regulating tissue gluconeogenic enzyme activity close to term?

    T3 is a physiological regulator of tissue gluconeogenic enzyme activity close to term and mediates, at least in part, the maturational effects of fetal plasma cortisol.

    regulation t3

  • Why are synthetic glucocorticoids like dexamethasone given to pregnant women threatened with pre-term delivery?

    They are given to improve the viability of their infants.

    clinical dexamethasone

  • What effect does maternal dexamethasone treatment have in ovine pregnancy?

    Maternal dexamethasone treatment increases the glucogenic capacity of both the mother and fetus, affecting glucose availability before and after birth.

    sheep dexamethasone

  • What are the main nutrient sources for the infant immediately after birth and for how long in most species?

    Glycogen and fat are the main nutrient sources immediately after birth for up to 24 hours in most species.

    nutrition neonate

  • After the initial 24 hours post-birth, where do most calories come from for the infant?

    Thereafter, calories come from the milk and remaining fuel reserves.

    feeding milk

  • How does milk composition vary between species and what is it related to?

    Milk fat and protein content varies widely between species and is related to the rate of growth and the need for insulation.

    composition milk

  • How are the mammary glands classified anatomically?

    They are classified as compound tubule-alveolar glands.

    anatomy mammary

  • What is the lobular structure of the breast and ductal drainage?

    The breast has 15 to 20 lobes of glandular tissue separated by adipose and collagenous connective tissue; each lobe is drained by its own lactiferous duct leading to the nipple with a lactiferous sinus.

    structure breast

  • What cells line alveoli and what is their function in lactation?

    Alveoli are lined with cuboidal epithelial cells that are responsible for milk synthesis and secretion during lactation.

    epithelium alveoli

  • Which cells surround the epithelial cells in alveoli?

    The epithelial cells are surrounded by myoepithelial cells.

    alveoli myoepithelial

  • From birth to puberty, what is the predominant structure of the mammary gland?

    • Predominantly lactiferous ducts with few, if any, alveoli
    development mammary

  • What effect do oestrogens have on the mammary gland during puberty?

    • Oestrogens cause ductal elongation
    oestrogen mammary puberty

  • What hormonal changes after ovulation shape the mature breast structure?

    • Progesterone and oestrogens result in the ductal-lobular-alveolar structure of the mature breast
    ovulation hormones mammary

  • How do steroids contribute to mammary gland morphology?

    • Steroids induce marked development of connective tissue and deposition of fat and may contribute to duct development
    steroids mammary

  • What triggers side-branching in the adult mammary gland?

    • Recurrent oestrous cycles in adulthood trigger side branching
    cycles mammary

  • How does growth hormone (GH) promote mammary ductal development?

    • GH induces IGF-1 expression in stromal and epithelial components, promoting ductal elongation and differentiation into terminal end buds
    mammary gh igf-1

  • Which hormones initiate lobule and terminal ductule development in early pregnancy?

    • Oestrogen, progesterone, human placental lactogen (hPL) and possibly insulin initiate lobule and terminal ductule development
    mammary pregnancy hpl

  • What happens to alveolar epithelial cells during late pregnancy?

    • Progesterone and oestrogen induce pronounced alveolar epithelial cell differentiation; steroid and prolactin levels are high
    alveoli pregnancy prolactin

  • What is the role of growth hormone (GH) in lactation?

    • GH acts directly on the mammary gland to stimulate milk synthesis
    lactation gh

  • What hormonal change at or after parturition is critical for initiation of lactation?

    • Withdrawal of oestrogens and progesterone, and possibly hPL, from the maternal circulation is critical to initiate lactation
    parturition lactation

  • How is milk stored and how is galactopoiesis maintained?

    • Milk is stored within the duct system; galactopoiesis is maintained by elevated prolactin levels through suckling
    milk prolactin galactopoiesis

  • Which neurons tonically inhibit prolactin secretion?

    • Tubero-Infundibular dopamine (TIDA) neurones tonically inhibit prolactin secretion
    prolactin neuroendocrine

  • How does suckling affect prolactin secretion?

    • Suckling inhibits TIDA activity, unleashing prolactin synthesis and secretion by lactotrophs in the adenohypophysis
    prolactin suckling

  • What are prolactin releasing factors (PRFs) role mentioned in the text?

    • PRFs, including VIP, may be involved in sensitising the actions of prolactin on lactotrophs
    prolactin vip

  • How are oxytocin and vasopressin stored in the neurohypophysis?

    • Oxytocin and vasopressin are synthesized by neuroendocrine cells in the PVN and SON and stored at nerve endings in the posterior pituitary
    oxytocin neurohypophysis vasopressin

  • What neural pathway triggers oxytocin release during nursing?

    • Nursing stimulates nipple receptors; sensory and spinal nerves carry impulses to the hypothalamus, stimulating oxytocin release
    oxytocin nursing

  • How does early-life intestinal microbiota relate to immune development?

    • The immune system develops during infancy and is highly related to the microbes that colonize the intestinal tract
    immune microbiome

  • How can maternal/neonatal microbiota affect offspring health?

    • Maternal/neonatal microbiota can shape offspring development, including risk of disease
    development microbiome

  • Which factors altering infant bacterial communities can influence disease risk?

    • Factors such as mode of delivery (vaginal or C-section) and excess antibiotics exposure can influence disease risk
    risk microbiome

  • What diseases can be influenced by early alterations in infant microbiota according to the text?

    • Altered bacterial communities can influence risk for allergic and inflammatory illnesses
    disease microbiome

  • What role does oxytocin play in lactation?

    Oxytocin initiates the milk ejection reflex by inducing contractions of the myoepithelial cells around the alveoli and the mammary ducts, initiating milk let-down.

    oxytocin lactation

  • What is colostrum?

    Colostrum is the first milk produced by the mother, differing from later milk in composition.

    lactation colostrum

  • How does colostrum differ from milk produced later in lactation?

    • Less fat and lactose
    • More proteins
    • More fat-soluble vitamins
    • Contains immunoglobulins (IgGs)
    composition colostrum

  • Which long-chain polyunsaturated fatty acids (LC-PUFAs) are present in human milk but not in cow's milk or most formulas?

    • Docosahexaenoic acid (DHA)
    • Arachidonic acid (AA)
    humanmilk fattyacids

  • What hypothesis is suggested about breastfeeding and IQ in relation to DHA?

    It has been suggested that the relationship between breastfeeding and IQ may be moderated by DHA or a genetic variant in FADS2.

    breastfeeding iq

  • Why do human neonates need immunological support from their mother?

    Human neonates are born with an immature and naïve acquired immune system and need maternal support for immediate protection and long-term immune development.

    immunity neonate

  • What prenatal immunological protection does the fetus receive?

    The fetus is supported by transplacental IgG antibodies.

    immunity placenta

  • Name major protective immune components present in human milk.

    • Secretory IgA (SIgA)
    • Lactoferrin
    • Lysozyme
    • Antiproteases
    • Complement
    immunity humanmilk

  • What is 'nesting' in the context of parental behaviour?

    Nesting refers to maternal behaviours like nest-site selection, nest building, and nest defence, and in humans may appear as cleaning and organising urges.

    nesting parenting

  • What function may nesting behaviours serve according to anthropological data?

    Nesting behaviours may serve a protective function at a critical period of development by helping mothers control the birthing environment.

    nesting anthropology

  • What did Harlow's primate studies demonstrate about early attachment?

    Harlow's work showed that comfort, companionship, and love are important for healthy development and attachment, beyond the provision of food.

    attachment harlow

  • How did variations in maternal care affect rat offspring in Meany's study?

    Offspring with high-quality maternal care (licking, grooming, nursing) showed increased HPA axis sensitivity to glucocorticoid negative feedback and a damped anxiety/stress response versus low-care offspring.

    epigenetics maternalcare

  • What symptom cluster do most mothers experience in the first weeks after birth commonly called 'baby blues'?

    • Anxiety
    • Irritability
    • Weepiness
    maternal postpartum

  • What hormonal change is thought to cause the 'baby blues' after childbirth?

    A sudden post-partum decrease in progesterone levels

    hormones postpartum

  • Which hormone has been shown to promote the induction of maternal care in mammals such as rodents and sheep?

    Oestradiol (an oestrogen) stimulates the onset of maternal behaviour soon after birth

    maternal oestrogen

  • What evidence supports a role for prolactin in maternal care behaviors like nursing and grooming?

    Genetic manipulations of the prolactin gene and prolactin receptor gene validate prolactin's role in maternal care

    maternal prolactin

  • Which hypothalamic and brain areas are acted on by prepartum increases in oestradiol and prolactin to induce maternal behaviours?

    • Medial pre-optic area (MPOA)
    • Locus coeruleus (LC)
    • Periaqueductal grey (PGA) nuclei
    hypothalamus maternal

  • What distinct neuroendocrine pattern linked to paternal behaviour was reported in mice by Stagkourakis et al.?

    • Low dopamine release
    • High circulating prolactin
    • Prolactin receptor-dependent activation of MPOA galanin neurons
    prolactin paternal

  • How did the neuroendocrine profile related to paternal behaviour differ between mice and rats in the study?

    Rats exhibited inverse profiles to mice for the reported parameters (dopamine release, prolactin levels, activation of MPOA galanin neurons)

    comparative paternal

  • What experimental manipulations changed paternal behaviour and serum prolactin in the rodent studies?

    • Optogenetic manipulation of dopamine neuron rhythms in mice
    • Injecting prolactin into non-paternal rat sires
    experiments paternal

  • What general mechanism do the findings suggest determines species-specific parental strategies?

    Distinct coupling schemes in a hypothalamic network producing different membrane potential oscillation frequencies set the hormonal axis tone and determine species-specific parental strategies

    mechanism hypothalamus

  • What conclusion do the combined findings provide about prolactin's role in parental behaviour?

    Prolactin and its actions on the hypothalamus can act as a driver of parental behaviour

    prolactin conclusion
Lernnotizen

Overview

Concise summary of neonatal physiology covered: energy substrates and their regulation at birth, mammary gland development and lactation control, milk composition and passive immunity, early-life microbiome and health outcomes, and neuroendocrine control of parental behaviour.

1. Neonatal energy substrates (first hours to days)

  • Key reserves: hepatic glycogen, muscle glycogen, and fat are the main fuels for the newborn.
  • Timeline: hepatic glycogen is mobilised rapidly after birth and is typically depleted by ~12 hours; muscle glycogen falls more slowly; fat catabolism supplies calories after glycogen is exhausted until feeding is established.
  • Immediately after birth and for up to ~24 hours, glycogen and fat supply energy; milk becomes the primary source thereafter.

2. Regulation of gluconeogenesis and enzyme maturation

  • Gluconeogenic enzymes (e.g., glucose-6-phosphatase (G6P) and PEPCK) increase before birth, enabling endogenous glucose production.
  • Hormonal drivers: increased cortisol, catecholamines, and glucagon, plus decreased insulin, activate gluconeogenic enzymes at birth.
  • Thyroid hormone (T3) is a physiological regulator near term: T3 rises prepartum and stimulates G6P and PEPCK in liver and kidney.
  • Experimental evidence: fetal adrenalectomy prevents prepartum enzyme increases; exogenous cortisol or T3 can prematurely induce them.
  • Clinical relevance: antenatal synthetic glucocorticoids (e.g., dexamethasone) given to women at risk of preterm delivery raise glucogenic capacity in mother and fetus and improve neonatal metabolic stability.

3. Mammary gland structure and development

  • Anatomy: the breast is a compound tubulo‑alveolar gland with 15–20 lobes, each drained by a lactiferous duct that opens at the nipple.
  • Alveoli (clustered into lobules) contain cuboidal epithelial cells that synthesise milk, surrounded by myoepithelial cells that contract to eject milk.
  • Development stages:
  • Childhood: mainly ducts present.
  • Puberty: oestrogens promote ductal elongation; progesterone with oestrogens forms the mature ductal–lobular–alveolar structure.
  • GH/IGF-1 supports ductal growth and differentiation.
  • Pregnancy: oestrogen, progesterone, human placental lactogen (hPL) and insulin drive lobulo‑alveolar maturation; prolactin and GH stimulate milk synthesis.
  • Initiation of lactation requires withdrawal of oestrogen and progesterone at parturition; continued milk production (galactopoiesis) depends on suckling-induced prolactin.

4. Milk let-down and neuroendocrine control

  • Milk ejection reflex: nipple stimulation sends sensory signals to hypothalamus, triggering oxytocin release from the posterior pituitary.
  • Oxytocin causes myoepithelial contraction around alveoli and ducts, producing milk let-down so the neonate can feed.
  • Prolactin (regulated by TIDA dopamine neurons) controls milk synthesis: suckling inhibits dopamine inhibition, increasing prolactin secretion; prolactin-releasing factors may modulate this.

5. Milk composition and passive immunity

  • Colostrum: first milk, lower in fat and lactose but richer in proteins, fat-soluble vitamins, and immunoglobulins (especially SIgA).
  • Human milk contains long-chain polyunsaturated fatty acids (LC-PUFAs) such as DHA and arachidonic acid (AA), which are low or absent in cow's milk and many formulas.
  • Protective factors in milk: SIgA, lactoferrin, lysozyme, antiproteases, and complement support innate mucosal immunity of the neonate.
  • Transplacental IgG also provides early systemic passive immunity before milk-borne protection takes effect.

6. Early-life microbiome and infant feeding outcomes

  • Gut colonization shapes immune development; maternal and early-life factors (mode of delivery, antibiotics) alter microbiota and affect disease risk.
  • Breastfeeding is associated with lower rates of infectious morbidity (e.g., otitis media, GI and respiratory infections) and possibly reduced obesity risk; cognitive outcome studies show mixed results and may be influenced by LC-PUFAs and genetics.

7. Parental bonding, behavioural effects, and epigenetics

  • Nesting and other preparatory behaviours are common across mammals and may provide environmental control during childbirth and early care.
  • Classic work (Harlow) emphasised that maternal contact and comfort—not just food—are crucial for healthy social and emotional development.
  • Maternal care can cause long-lasting effects via epigenetic and neuroendocrine programming: rodent studies (Meaney lab) show high maternal licking/grooming leads to reduced stress reactivity in offspring through altered HPA axis sensitivity.
  • Parental effects can be transmitted across generations and via both maternal and paternal lines.

8. Neuroendocrinology of parental behaviour

  • Postpartum mood: many mothers experience the "baby blues", likely linked to sudden postpartum drops in progesterone.
  • Oestradiol and prolactin promote onset of maternal behaviours by acting on hypothalamic regions (e.g., medial preoptic area (MPOA), locus coeruleus, periaqueductal grey).
  • Genetic studies manipulating prolactin and prolactin receptor confirm prolactin's role in nursing and grooming in rodents.

9. Neurobiology of paternal behaviour — experimental insights

  • Species differences in paternal care can be driven by hypothalamic neuroendocrine network dynamics.
  • A rodent study found that low dopamine release, high circulating prolactin, and activation of MPOA galanin neurons promote paternal care in mice; opposite profiles occur in rats.
  • Manipulating dopamine neuron oscillations or prolactin levels causally changed paternal behaviour, showing prolactin can drive paternal caregiving when the network permits.

10. Clinical and practical implications

  • Antenatal corticosteroids (e.g., dexamethasone) improve fetal glucogenic enzyme maturity and neonatal metabolic resilience for preterm infants.
  • Encourage early breastfeeding to supply passive immunity, LC-PUFAs, and microbiome-promoting factors; consider that formula feeding is associated with higher infection rates and metabolic risks in many studies.
  • Maternal mental health and support for parental behaviours are important because hormonal shifts and early care strongly influence offspring stress regulation and long-term outcomes.

Key definitions and takeaways

  • Galactopoiesis: maintenance of milk production, driven by prolactin and suckling.
  • Colostrum: nutrient- and antibody-rich first milk that provides passive immunity.
  • G6P & PEPCK: key gluconeogenic enzymes that rise before birth under endocrine control.
  • MPOA: hypothalamic area central to parental behaviour regulation.

Quick study checklist

  • Know the three main neonatal fuel reserves and their time courses after birth.
  • Understand hormonal triggers that activate gluconeogenesis at birth (cortisol, T3, glucagon, catecholamines, ↓ insulin).
  • Be able to describe mammary gland structure and the hormonal control of lactation initiation and maintenance.
  • List the main immune components of breast milk and the functions of colostrum.
  • Appreciate how early microbiome establishment and parental care affect long-term health and behaviour.