Abstract
Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (P<0.001) and deep infiltrating endometriotic lesions of uterosacral ligament (P = 0.028)compared with glandular epithelial cells of the endometrium from women with endometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (P<0.001, P<0.001, respectively). NFDs of Anti-TH (+) endometriosis-associated sympathetic nerve of peritoneal endometriosis (p<0.001) and deep endometriosis of uterosacral ligament (p<0.001) were significantly lower than NFDs of para-endometriotic sympathetic nerve. Our results suggest that Sema 3A may contribute to the regulation of aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis.
Highlights
Endometriosis is a chronic, inflammatory, estrogen-dependent benign gynecological disease characterized by the presence of endometrial glands and stromal cells outside the uterine cavity
We further investigated the distribution of PGP9.5-immunoactive or Tyrosine Hydroxylase-immunoactive sympathetic nerve fibers in/ near the endometriotic lesions and analyze the association between expression of semaphorin 3A (Sema 3A) and the density of these nerve fibers
Higher immunostaining of Sema 3A and Plexin A1 were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041 and p = 0.025, respectively) than those without endometriosis
Summary
Endometriosis is a chronic, inflammatory, estrogen-dependent benign gynecological disease characterized by the presence of endometrial glands and stromal cells outside the uterine cavity. It is often associated with infertility and pelvic pain, affecting 10–15% of women of childbearing age worldwide [1]. The mechanisms underlying endometriosis-associated-pain remain to be further investigated. Recent studies have shown endometriotic lesions develop newly formed sensory and autonomic nerve fibers in rat models and in women with endometriosis [2,3,4], often in close contact with endometriotic implants and accompany with the immature blood vessels that vascularize the ectopic growth [5]. The density of endometriosis-associated nerve fibers were correlative with the severity of pain in women with endometriosis [6], suggesting a direct association between pain and nerve fiber density
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