Maternal Adaptation

Lecture 11: Placental Function, Maternal Adaptation to Pregnancy, and Neonatal Physiology

Placental Structure and Function

  • Definition: The placenta is an organ with multiple roles.

    • Functions:

    • Metabolic interchange between mother and fetus

    • Endocrine activity

    • Components: Composed of maternal and fetal tissues.

    • Placental fluid: The fetus is enveloped in protective, fluid-filled membranes (amnion).

    • Mid-gestation: When skin forms a keratin layer:

      • Becomes watertight, requiring fluids to be delivered via blood.

    • Late gestation: The majority of fluid consists of waste (water, salts, proteins, debris).

Placental Blood Supply

  • Dependence on Species: The structure of the placenta varies among species and dictates its blood supply.

  • Restrictiveness:

    • Controls passage of substances:

    • No cells or large molecules/proteins can cross.

    • Caution: Some small structures do pass freely (notably certain drugs, alcohol, and antibiotics).

Placental Transfer

  • Complex Mechanism: Substances must permeate multiple cell lipid bilayers and fluid compartments.

  • Diffusion:

    • Gasses (O2, CO2): Pass via simple diffusion.

    • Water and Electrolytes:

    • Traveling methods:

      • Transcellular: through cells

      • Paracellular: between cells

    • Electrolytes (Na, Cl, Ca, P, K) can move:

      • In solution: with water to reach equilibrium

      • Against gradient: via energy-dependent ATP channels.

Nutrient/Molecule Passage

  • Proteins: Generally too large to cross. Thus, fetuses synthesize proteins from maternal amino acids (e.g., TSH, ACTH, GH, Insulin).

  • Antibodies:

    • Example: IgG is transported in species with hemochorial and endotheliochorial placentas.

  • Lipids:

    • Do not cross placenta easily; hydrated via carriers in blood.

    • Transport Mechanism: Placenta hydrolyzes triglycerides and phospholipids to facilitate crossing.

    • Small lipophilic molecules (steroids) can pass freely.

  • Vitamins and Minerals:

    • Pass if soluble or lipophilic.

    • Iron (Fe) from mother utilizes transferrin/uteroferrin carriers for transport.

Specific Substances Transferred

  • Glucose:

    • Transferred via facilitated diffusion from mother to fetus using GLUT carriers at the cell.

    • Serves as the primary energy source for the fetus; occurs at higher concentrations in maternal circulation compared to fetal.

Fetal Oxygen Supply

  • Maternal RBCs: Do not cross the placenta.

  • Oxygen Supply:

    • Maternal oxygen is provided to fetus, which bypasses lungs via ductus arteriosus shunt.

    • High fetal O2 requirements for cellular respiration; body lacks storage capacity for oxygen.

  • RBC Production:

    • Occurs in fetal spleen; fetal liver produces hemoglobin (Hb) to facilitate O2 and CO2 exchange in placental capillaries.

    • Fetal heart and circulatory system begin pumping blood to the placenta and other organs by the second trimester.

Placenta as a Barrier for Disease

  • Sterility of Placental Fluids: Placental fluids are kept sterile.

  • Cell Junctions: Tight junctions and multiple cellular layers prevent most pathogens from passing through.

  • However, maternal infections can still impact fetal health:

    • Microbial Invasion:

    • Certain bacteria (e.g., syphilis, listeria) can overcome placental protections.

    • Viruses: Most are prevented from crossing, but some (e.g., German measles, cytomegalovirus) can cause significant harm.

    • Protozoans (e.g., Toxoplasmosis) can pose a risk to fetal development.

Infectious Causes of Abortion in Dogs and Cats

  • Canine:

    • Brucella canis, Streptococci, Toxoplasma gondii, Canine herpesvirus, among others.

  • Feline:

    • Includes viruses like Feline leukemia and Feline panleukopenia.

Maternal Adaptation to Pregnancy

  • Physiological Changes: Necessary adjustments occur in maternal physiology to accommodate the developing offspring (not parasitic but same species).

  • Role of the Placenta:

    • Continuously modulates maternal physiology to maintain pregnancy.

    • Secretes hormones vital for maternal adaptations and offers an interface for nutrient exchange.

Maternal Changes During Gestation

  • Evident Changes:

    • Most maternal tissues and organs adapt to pregnancy.

  • Blood Flow/Volume: Increases during gestation.

    • Heart size increases, and vasodilation enhances blood volume by approximately 30%.

    • Increased blood circulation nourishes all organs, including the uterus.

  • Oxygen Requirements:

    • Increased blood volume translates to higher oxygen needs, necessitating the production of more RBCs.

    • Increased lung volume to accommodate these needs.

Maternal Metabolic Changes During Gestation

  • Calcium Needs:

    • Increased calcium needed for fetal skeleton development:

    • Enhanced absorption in the gut and retention in kidneys.

    • Increased mobilization from maternal skeleton.

  • Energy Requirements: Rise significantly by the second trimester.

    • Increased fat storage and insulin sensitivity in adipose tissue.

  • Liver Changes:

    • Enlarges and accumulates glycogen, providing extra energy (fat and glucose) for the growing fetus.

    • Changes in insulin sensitivity, leading to decreased lipolysis and gluconeogenesis.

  • Appetite Increase: Maternal appetite usually increases during late gestation.

Maternal System Changes

  • Digestive System:

    • Slowed gut passage rate observed.

  • Immune System:

    • Tightly regulated to avoid reactions against paternal antigens in the conceptus.

  • Mammary Gland Development: Significant maturity and development occur.

Maternal Effects on Fetal Development

Early Concept of Fetal Programming

  • Historical Context: During the Dutch famine of WW2 (1944-’45), pregnant women consuming about 500-600 calories/day gave birth to lower birthweight babies, affecting even subsequent generations.

  • Risks: Slow prenatal growth is a major factor for various non-communicable diseases (e.g., Intrauterine Growth Restriction - IUGR).

  • Stress Factors: Severe stressors (e.g., famine, disasters, war) can negatively impact fetal growth.

Epigenetics

  • Definition: Changes in gene expression without altering the genetic code, termed "epigenetics".

  • Mechanism: This occurs via methylation of DNA or histone proteins, altering the availability of genes for transcription, influenced by external environments and thus becoming heritable.

Comparison of Maternal and Paternal Effects

  • Maternal Imprinting: The uterine environment influences fetal growth, demonstrated in a study by Walton and Hammond.

    • Crossbreeding Experiment: Large (Shire) and small (Shetland) horses showed that maternal uterine conditions impacted birth weight and size up to 3 years post-birth.

Fetal Imprinting Through Uterine Environment

  • Impact of Maternal Size: The maternal uterine conditions during pregnancy affect birth weight; post-natal growth remains unaffected.

Mechanism of Fetal Programming

  • Changing Environment: Altering maternal conditions shifts the uterine environment, altering fetal gene expression.

    • Nutrition: Various maternal nutrition models can negatively affect fetal “program” and lead to heritable changes.

    • Factors associated with negative impacts include reduced maternal or placental blood flow, placental size, and early fetal size reduction (IUGR).

Uterine Effects on Fetal Development

  • Litter Bearing Species: In such species, uterine space limitations cause competition for resources amongst multiple fetuses.

Neonatal Physiology

Fetus Control of Parturition

  • Maturity of Hypothalamic-Pituitary-Adrenal Axis: As the fetus grows, this axis matures, leading to an increase in fetal adrenal size.

  • Triggering Labor: Evidence suggests that limiting space is a stress factor that initiates labor processes:

  • Cortisol Release: The fetal adrenal releases cortisol which stimulates the placenta to produce prostaglandins, resulting in a decline in progesterone levels leading to uterine contractions.

Late Fetal Development

  • Fetal Maturity: Many immature species are born with eyelids fused, yet eye development persists post-birth.

  • Acoustic Response: Evidence indicates that fetuses can hear and contract muscles in response to stimuli prior to birth.

Maturity at Birth

  • Precocial Species: Species like lambs (cows, horses, sheep, pigs) are born relatively mature and can survive independently.

  • Altricial Species: Species such as dogs, cats, primates, and rodents are born immature with closed eyes, opening by approximately 2 weeks.

Birth in Litter Bearing Species

  • Many altricial species (like mice, rats, rabbits, dogs) have unique reproductive complexities, yet some, like pigs, can be classified as precocial.

Differences in Maturity

  • Precocial: Capable of independent survival upon birth; larger size typically links to higher maturity at birth.

  • Altricial: Need maternal protection, can vary significantly in developmental attributes (e.g., brain development, muscle coordination, thermoregulation).

    • Newborns in litters exhibit behaviors in seeking warmth and rotating spots for optimal temperature.

Fetal Transition to Life Outside Mother

  • Energy Needs: Newborns require synthesized liver glycogen for energy once umbilical cord circulation ceases.

  • Oxygen Needs: Newborn lungs must rapidly adapt to sustain gas exchange after birth.

  • Gut Adaptation: Adjustments in the gut are required to effectively absorb milk nutrients.

  • Kidneys and Thermoregulation: Newborns must quickly manage water and ion balance, and their bodies exhibit better tolerability to brief asphyxia, trauma, and hypothermia relative to adults.

Newborn Survival

  • Survival linked to lung enzyme production for surfactant, vital for inflation and respiratory function post-birth.

  • Mammalian fetuses store energy as glycogen yet exhibit variability in fat accumulation.

Species Differences in Neonatal Fat

  • Fat storage begins early in the second trimester for mammalian fetuses.

  • The synthesis of fatty acids from glucose leads to varying fat storage:

    • Composition at Birth by Species:

    • Human: 16%

    • Guinea pigs: 10%

    • Rabbits: 6%

    • Sheep: 3%

    • Pigs: 1%

    • Rats: 1%