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 uterus and uterine artery which origin remains still unclear. It is well established that the density of sympathetic innervation is regulated by the levels of peptidergic diffusible growth factors, especially nerve growth factor (NGF). Whether a decrease of NGF and/or its signal-transducing receptor TrkA are involved in this physiological denervation of the uterine artery during pregnancy has not been analyzed. The aim of the present study is to analyze this topic on human uterine artery using ELISA, Western blotting and immunohistochemistry (associated to quantitative image analysis). The material was obtained from surgical pieces (hysterectomy) of non-pregnant and pregnant 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 (PGP 9.5 and NFP) or Schwann cell (S-100 protein) markers was significantly reduced (p<0.05) in the uterine artery from pregnant woman. On the other hand, 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 denervation occurring in the uterine artery during pregnancy is related to a decrease in the availability of NGF by nerve fibers, and to the impossibility to mediate its effect due to a remarkable decrease in the signal-transducing TrkA receptor.