Pregnancy-induced denervation of the human uterine artery correlates with local decrease of NGF and TrkA

Area of Science:

• Reproductive Biology
• Neuroscience
• Vascular Physiology

Background:

• Pregnancy involves temporary denervation of the uterus and uterine artery, but the cause is unclear.
• Nerve growth factor (NGF) regulates sympathetic innervation density.
• The role of NGF and its receptor TrkA in pregnancy-related uterine artery denervation is not well understood.

Purpose of the Study:

• To investigate the involvement of decreased nerve growth factor (NGF) and its receptor TrkA in the physiological denervation of the human uterine artery during early pregnancy.
• To analyze NGF and TrkA levels and distribution in uterine arteries of pregnant and non-pregnant women.

Main Methods:

• Human uterine artery samples from non-pregnant and pregnant women (4-16 weeks gestation) obtained via hysterectomy.
• Analysis using ELISA, Western blotting, and immunohistochemistry with quantitative image analysis.
• Assessment of nerve fiber density using tyrosine hydroxylase, PGP 9.5, NFP, and S-100 protein markers.

Main Results:

• Significantly reduced density of sympathetic innervation (tyrosine hydroxylase) and general nerve fibers (PGP 9.5, NFP) in uterine arteries of pregnant women.
• Significantly decreased tissue levels of NGF and reduced density of TrkA receptor in uterine arteries from pregnant patients.
• Immunostaining confirmed reduced presence of NGF and TrkA in the uterine arteries of pregnant women.

Conclusions:

• The physiological denervation of the uterine artery during pregnancy is associated with reduced NGF availability and a significant decrease in the TrkA receptor.
• This reduction in NGF and TrkA likely impairs the signaling necessary for maintaining uterine artery innervation during pregnancy.