ABSTRACT
OBJECTIVE: To investigate neuronal remodeling processes in the uterine innervation, particularly a remodeling of sympathetic nerve fibers, as well as the role of estrogen in this modulation in adenomyosis. DESIGN: Retrospective case-control study. SETTING: University hospital endometriosis center. PATIENT(S): Forty-two patients with histologically proven adenomyosis and 19 patients without adenomyosis. INTERVENTION(S): Endometrial and myometrial tissue were immunohistochemically analyzed to further characterize the uterine innervation. MAIN OUTCOME MEASURE(S): Immunohistochemical analysis was used to identify PGP 9.5-, substance P-, and tyrosine hydroxylase-positive nerve fibers. The expression of the aromatase cytochrome P450 was evaluated in uterine tissue, and the expression of the estrogen receptor (ER) -α and ERß in uterine nerve fibers was analyzed. RESULT(S): Adenomyotic lesions are not innervated. The density of sympathetic nerve fibers in the myometrium of women with adenomyosis is reduced when compared with the nonadenomyosis group. The aromatase expression in the myometrium of women with adenomyosis was increased when compared with the control group. The ERα/ERß ratio is in trend shifted to the ERα side in the myometrial tyrosine hydroxylase-positive nerve fibers in adenomyosis compared to the controls. CONCLUSION(S): The disruption of the modulation of the uterine sympathetic innervation seems to be an important aspect in the pathogenesis of adenomyosis. Estrogen and its receptors seem to play a crucial role in the depletion of myometrial sympathetic nerve fibers.
Subject(s)
Adenomyosis/physiopathology , Adrenergic Fibers/drug effects , Adrenergic Fibers/physiology , Estrogens/pharmacology , Uterus/innervation , Adenomyosis/metabolism , Adenomyosis/pathology , Adrenergic Fibers/metabolism , Adrenergic Fibers/pathology , Adult , Aromatase/metabolism , Case-Control Studies , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Female , Gravidity/physiology , Humans , Menstrual Cycle/drug effects , Menstrual Cycle/metabolism , Menstrual Cycle/physiology , Middle Aged , Nerve Regeneration/drug effects , Parity/physiology , Pregnancy , Retrospective Studies , Uterus/drug effects , Uterus/metabolism , Uterus/physiopathologyABSTRACT
To investigate the involvement of neurotrophins and nerve fibres in the pathogenesis of adenomyosis, we performed a retrospective, clinical study. Hysterectomy specimens from 40 patients with histologically proven adenomyosis and from 20 patients without adenomyosis or endometriosis were used for immunohistochemical analysis. In order to investigate neurotrophic properties in adenomyosis, the antibodies against nerve growth factor (NGF), neurotrophin 3 (NT-3), the high-affinity NGF receptor (TrkA), the low-affinity neurotrophin receptor (p75(NTR)), the neuronal marker S100 (for myelinated nerve fibres) and protein gene product 9.5 (PGP9.5; for intact nerve fibres) were used. There was no significant difference in the NGF, NT-3 and p75(NTR) expression in the myometrium or endometrium between the adenomyosis and the control group. The nerve fibre density (S100, PGP9.5 and p75(NTR)) did not significantly differ between the adenomyosis and control group, the nerve fibre density of the adenomyosis group was tendentially decreased when compared with the nonporous control group. The present study suggests that endometrial and uterine neurotrophin expression and endometrial innervation are not altered in adenomyosis; however, women with adenomyosis or with adenomyosis/endometriosis tendentially had less myometrial nerve fibres than the control group.
