Disruption of the estrogen-dependent sympathetic nerve fibers remodelling in adenomyosis uteri

Abstract

In rodents, the sympathetic innervation is depleted in estrogen-rich phases of the cycle and restored in estrogen-poor phases. A decrease of PGP-9.5-positive nerve fibers (NF) at the endometrial-myometrial interface of adenomyosis (AM) is described. However, NF are present in some AM samples, suggesting a dysfunctional regulation of hormone-dependent changes in uterine innervation in AM. In order to investigate the estrogen-dependent remodeling of uterine innervation in AM, we characterized sympathetic NF in 42 AM specimens by using immunohistochemistry. Furthermore, we analyzed the interaction of sympathetic NF and estrogen receptor α and β in AM patients. The myometrium of women with AM showed less sympathetic NF than the control group ( p < 0.01). The control group showed less sympathetic NF in the secretory than in the proliferative phase. In AM we could not find a cycle-dependent modulation of sympathetic NF. The double staining showed an expression of estrogen receptor α and β in sympathetic NF. In healthy myometrium; a cycle-dependent modulation of the innervation was seen, but in AM it seems to be disturbed. This study demonstrated a reduction of sympathetic myometrial NF in AM. The sympathetic outgrowth is reduced in rodents during estrogen-rich phases, suggesting that estrogen modulates the sympathetic innervation. We could demonstrate an estrogen receptor α and β expression by sympathetic NF, suggesting an estrogen-dependent depletion of sympathetic NF. The uterus seems to go through an estrogen-dependent remodeling. In AM, this remodeling seems to be disturbed since we were able to demonstrate a reduction of sympathetic NF in all cycle phases.