Endometriosis and adenomyosis: shared pathophysiology.

Area of Science:

• Gynecology
• Reproductive Biology
• Cell Biology

Background:

• Endometriosis and adenomyosis are distinct yet closely related gynecological disorders.
• Their pathophysiologies exhibit significant similarities, originating from the eutopic endometrium.
• Both conditions involve endometrial glandular epithelial cells with somatic mutations and stromal cell abnormalities.

Purpose of the Study:

• To elucidate the shared molecular mechanisms underlying endometriosis and adenomyosis.
• To compare the genetic and epigenetic profiles of epithelial and stromal cells in both disorders.
• To understand the role of specific mutations and epigenetic defects in disease progression.

Main Methods:

• Comparative analysis of genetic variants in epithelial cells.
• Assessment of epigenetic abnormalities in stromal cells.
• Investigation of nuclear receptor expression and steroid hormone action.

Main Results:

• Activating KRAS mutations are prevalent in endometriotic epithelial cells; adenomyotic epithelial cells almost exclusively harbor KRAS mutations.
• Stromal cells in both conditions display similar epigenetic abnormalities, including altered nuclear receptor expression.
• Epigenetic defects lead to increased local estrogen biosynthesis and abnormal estrogen receptor-β action.
• Deficient progesterone receptor expression causes progesterone resistance in both endometriosis and adenomyosis.

Conclusions:

• Endometriosis and adenomyosis share common origins and molecular drivers, including KRAS mutations and stromal epigenetic dysregulation.
• Aberrant estrogen and progesterone signaling pathways are critical in the pathogenesis of both disorders.
• Targeting these shared pathways may offer therapeutic strategies for both endometriosis and adenomyosis.