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

Pregnancy induces transient and reversible denervation of the mammalian ute rus and uterine artery which origin remains still unclear. It is well estab lished that the density of sympathetic innervation is regulated by the leve ls of peptidergic diffusible growth factors, especially nerve growth factor (NGF). Whether a decrease of NGF and/or its signal-transducing receptor Tr kA are involved in this physiological denervation of the uterine artery dur ing pregnancy has not been analyzed. The aim of the present study is to ana lyze this topic on human uterine artery using ELISA, Western blotting and i mmunohistochemistry (associated to quantitative image analysis). The materi al was obtained from surgical pieces (hysterectomy) of non-pregnant and pre gnant women from 4 to 16 weeks of gestation. The density of innervation for tyrosine hydroxylase assessed in whole mount samples of uterine artery, as well as the density of nerve fibers identified with other general nerve (P GP 9.5 and NEP) or Schwann cell (S-100 protein) markers was significantly r educed (p<0.05) in the uterine artery from pregnant woman. On the other han d, the tissular levels of NGF, the density of TrkA, and the immunostaining for both NGF and TrkA, were significantly reduced in uterine arteries from pregnant patients. These results strongly suggest that the physiological de nervation occurring in the uterine artery during pregnancy is related to a decrease in the availability of NGF by nerve fibers, and to the impossibili ty to mediate its effect due to a remarkable decrease in the signal-transdu cing TkRA receptor.