Low aromatase activity in microsomes from complete hydatidiform mole

Area of Science:

• Biochemistry
• Reproductive Endocrinology
• Gynecologic Pathology

Background:

• Complete hydatidiform mole (CHM) is a placental abnormality lacking maternal genetic material.
• Steroidogenesis is altered in CHM, making aromatase activity a key area of investigation.
• Understanding these alterations is crucial for explaining pregnancy complications associated with CHM.

Purpose of the Study:

• To compare the kinetic parameters of aromatase in CHM and normal early placenta (NEP).
• To investigate the impact of altered aromatase activity on steroidogenesis in CHM.
• To elucidate the role of altered steroidogenesis in the clinical presentation of CHM.

Main Methods:

• Microsomal preparations from CHM and NEP tissues were used.
• Aromatase activity was measured by the conversion of [3H]testosterone to [3H]estradiol and [3H]estrone.
• Kinetic parameters (Km, Vmax) and inhibitor (aminoglutethimide) potency were determined.

Main Results:

• Aromatase exhibited similar Michaelis constant (Km) for testosterone in CHM (33 nmol/L) and NEP (17 nmol/L).
• The enzyme inhibitor aminoglutethimide showed similar potency in both tissues.
• Enzyme efficiency (Vmax/Km) was 17-fold lower in CHM compared to NEP, indicating reduced aromatase capacity.

Conclusions:

• CHM trophoblast tissue has a significantly decreased capacity for estrogen formation due to reduced aromatase efficiency.
• Lower estrogen production may lead to increased intravesicular testosterone, inhibiting progesterone formation.
• These findings offer a biochemical explanation for low progesterone levels in molar pregnancies, potentially influencing spontaneous expulsion.