Functions of Placenta

Functions of Placenta

This lecture discusses the various functions of the placenta, focusing on its metabolic and endocrine roles, and is important for undergraduate understanding and MCQs in NEET, NEXT, and INI-CET exams.

Overview of Placental Functions

The placenta performs several critical functions, primarily:

  1. Metabolic and Endocrine Functions: Including hormone production.
  2. Substrate Transfer: Moving substances from mother to fetus.
  3. Gas Exchange: Facilitating the exchange of gases.

Metabolic Functions of Placenta

The metabolic functions are crucial for fetal development, focusing on glucose, fatty acids, and amino acids.

Glucose Transfer
  • The fetus relies on the mother for glucose, its primary energy source.
  • The placenta transfers glucose via facilitated diffusion using GLUT receptors, mainly GLUT1 and GLUT3.
  • The placenta stores glycogen, acting as a reserve for the fetus.
  • Glycogenin enzyme is vital for these glucose-related functions.
Fatty Acid Transfer
  • Maternal triglycerides are broken down into fatty acids by lipase.
  • The placenta transfers these fatty acids to the fetus, which uses them for energy and cholesterol synthesis.
  • Cholesterol is a substrate for hormone production.
Amino Acid Transfer
  • Amino acids are essential for fetal growth and are transferred via the placenta.
  • The placenta also produces proteins, with production rates increasing from 1.5 g/day in the first trimester to 7.5 g/day in the third trimester.
Waste Removal
  • Lactate, a metabolic waste product, is transferred from the placenta to the mother.

Endocrine Functions of Placenta

The placenta produces both steroid and peptide hormones crucial for maintaining pregnancy and supporting fetal development.

Steroid Hormones
  • Estrogen
  • Progesterone
  • Corticosteroids
Peptide Hormones
  • HCG (Human Chorionic Gonadotropin)
  • HPL (Human Placental Lactogen)
  • CRH (Corticotropin-Releasing Hormone)
  • IGF (Insulin-like Growth Factor)
  • VEGF (Vascular Endothelial Growth Factor)
  • Placental Growth Factor
  • Soluble FMS-like Tyrosine Kinase-1 (sFlt-1)

Human Chorionic Gonadotropin (HCG)

Production and Structure
  • Mainly produced by syncytiotrophoblast.
  • Glycoprotein hormone with high carbohydrate content.
  • Molecular weight ranges from 36,00036,000 to 40,00040,000 Daltons.
  • Composed of alpha and beta subunits.
Subunits
  • Alpha subunit:
    • Gene located on chromosome 6.
    • Non-specific, shared with LH, FSH, and TSH.
  • Beta subunit:
    • Gene located on chromosome 19.
    • Specific; used in pregnancy tests.
Pregnancy Tests
  • Beta subunit is tested in both urine and serum pregnancy tests due to its specificity.
  • Alpha subunit similarity affects thyroid physiology during pregnancy (covered in OBGYN and Pharma integration).
Functional Similarity
  • Morphologically similar to LH, FSH, and TSH.
  • Functionally similar to LH; acts via LH receptors.
  • Used in IVF cycles to trigger ovulation by mimicking the LH surge.
Detection and Levels
  • Secretion begins in pre-implantation embryo.
  • Earliest detection in blood: 8 days post-fertilization.
  • Correlates to approximately day 22 of a 28-day cycle or 5-6 days before a missed period.
Sensitivity of Tests
  • Serum quantitative HCG tests are most sensitive, detecting levels as low as 1-2 mIU/mL.
  • Negative pregnancy test: HCG levels below 5 mIU/mL.
  • Fluorescent immunoassay (FIA) is the most sensitive serum test, followed by radioimmunoassay (RIA).
  • At 4 weeks (day of missed period), serum HCG levels are around 200 mIU/mL, while urine levels are approximately 50 mIU/mL.
HCG Dynamics in Early Pregnancy
  • HCG levels double every 48 hours (1.5-2 days) in early pregnancy.
  • Increase ranges from 33% to 65%.
  • Maximum levels are seen at 10 weeks (60-80 days).
  • Minimum levels are observed around 16-20 weeks.
  • T half of HCG is 36 hours, distinct from the doubling time.
  • Significance of HCG testing is primarily in the first trimester.
Abnormal Pregnancy Indications
  • In viable intrauterine pregnancies, HCG levels increase by at least 33% every 48 hours.
  • Slow rise (increase less than 33%) may indicate ectopic pregnancy.
  • Decreasing levels suggest a non-viable intrauterine pregnancy.
Conditions with Altered HCG Levels
  • Higher than expected:
    • Underestimated gestational age.
    • Multi-fetal pregnancy.
    • Rh-negative pregnancy (erythroblastosis fetalis).
    • Gestational trophoblastic diseases (molar pregnancy, choriocarcinoma).
    • Down syndrome (trisomy 21).
  • Lower than expected:
    • Overestimated gestational age.
    • Abortion.
    • Ectopic pregnancy.
    • Trisomies other than Down syndrome.
Ectopic Pregnancy and HCG
  • Absolute levels are lower than in intrauterine pregnancies at the same gestational age.
  • HCG levels show a slow rise (less than 33% increase in 48 hours).
Functions of HCG
  • Maintains corpus luteum during pregnancy.
  • Stimulates testosterone release from Leydig cells in male fetuses.
  • Acts as a smooth muscle relaxant.
  • Prevents fetal rejection.
  • Amniotic fluid levels of HCG are similar to maternal plasma levels.
  • Placental GnRH stimulates HCG production.
  • Cleared 70% by the liver and 30% by the kidney.

Corpus Luteum

Maintenance and Role
  • In non-pregnant females, maintained by LH and undergoes luteolysis monthly.
  • In pregnancy, HCG prevents luteolysis.
  • HCG maintains corpus luteum in pregnancy, preventing apoptosis.

Human Placental Lactogen (HPL) / Human Chorionic Somatomammotropin (HCS)

Structure and Similarity
  • Synthesized by syncytiotrophoblast.
  • Single, non-glycosylated polypeptide chain.
  • Molecular weight: 22,00022,000 D.
  • 96% structural resemblance to growth hormone and 65% to prolactin.
Production and Levels
  • Detected by 3 weeks of pregnancy.
  • Levels increase throughout pregnancy, peaking at 36 weeks.
  • Serves as a marker for placental functioning.
  • t1/2t_{1/2}: 20-30 minutes.
  • Production rate at term: 1 g/day.
Distribution
  • Maximum levels are seen in maternal plasma, then amniotic fluid, and least in fetal blood.
Functions
  • Provides glucose to the fetus by:
    • Causing insulin resistance in the mother.
    • Promoting lipolysis.
  • Angiogenic, but has no role in breastfeeding.
Insulin Resistance
  • Increases with gestation due to HPL.
  • Significant insulin resistance beyond 24 weeks can lead to gestational diabetes.
  • Testing for gestational diabetes is best between 24-28 weeks.
Hormonal Influence on Insulin Resistance
  • Mainly due to HPL, with contributions from estrogen, progesterone, and cortisol.
  • HCG does not play a role in insulin resistance.
Metabolic Effects
  • Fasting hypoglycemia and postprandial hyperglycemia in pregnant females.

Insulin-like Growth Factors (IGF)

Production and Function
  • Placenta produces IGF-1, IGF-2, and IGF binding proteins.
  • IGF-2 binds to IGF-1, promoting fetal growth.
  • Key hormone for fetal growth (not growth hormone).

Corticotropin-Releasing Hormone (CRH)

Regulation and Impact
  • Maternal glucocorticoids have negative feedback on maternal hypothalamus but positive feedback on placental CRH.
  • Placental CRH is produced throughout pregnancy, bound to CRH binding protein.
  • At term, CRH binding proteins decrease, increasing free placental CRH.
  • Activates fetal HPA axis, leading to labor.
  • Acts as a placental clock.
Preterm Labor
  • Maternal stress can prematurely activate the placental CRH pathway, leading to preterm labor.

Vascular Endothelial Growth Factor (VEGF) and Placental Growth Factor (PIGF)

Roles
  • VEGF: Angiogenesis in the first trimester.
  • PIGF: Angiogenesis in the third trimester.

Soluble FMS-like Tyrosine Kinase-1 (sFlt-1)

Function
  • Binds to VEGF and PIGF, inhibiting angiogenesis and vasodilation.
Preeclampsia
  • Imbalance with increased sFlt-1, leading to vasoconstriction and preeclampsia.
  • Predictors of preeclampsia include sFlt-1, VEGF, and PIGF imbalances.
  • sFlt-1 increases, while VEGF and PIGF decrease in preeclampsia.

Steroid Hormones

Estrogen
  • Placenta cannot synthesize estrogen from maternal precursors due to the lack of 17 alpha-hydroxylase enzyme.
  • Uses fetal adrenal gland-produced DHEA sulfate instead.
  • Enzymes involved: sulfatase, 3β-HSD, and aromatase.
  • Contributes to initiating uterine contractions.
Role at Term
  • Estrogen production and estrogen receptors increase at term.
Anencephaly
  • Absent or hypoplastic adrenal gland leads to decreased DHEA sulfate.
  • Results in decreased estrogen production, potentially causing post-term pregnancy.
Types and Significance
  • Most common estrogen in pregnancy: Estradiol (E2).
  • Most specific estrogen in pregnancy: Estriol (E3).
Clinical Conditions
  • Increased estrogen:
    • Erythroblastosis fetalis (Rh-negative pregnancies).
    • Maternal androgen- or estrogen-producing tumors.
  • Decreased estrogen:
    • Intrauterine fetal demise.
    • Anencephaly.
    • Placental sulfatase or aromatase deficiency.
    • Down syndrome.
Aromatase Deficiency
  • Leads to decreased estrogen and post-term labor.
  • Increases androgen levels, causing hirsutism in the mother.
  • Can result in ambiguous genitalia in a female fetus.
Progesterone
  • Produced using mother's LDL cholesterol.
  • Production starts at ≥8 weeks (luteal-placental shift).
  • Role: Smooth muscle relaxant, preventing fetal expulsion.
Labor Onset
  • Requires functional withdrawal of progesterone: progesterone levels remain the same, but the receptors decrease.
Preterm Labor Prevention
  • Administering progesterone can help prevent preterm labor.
Low Progesterone Levels
  • Can lead to abortion (luteal phase defect).
  • Managed by administering progesterone.
Function and Production
  • Daily production rate is approximately 250 mg per day.