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Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis.

Liang Y, Wang W, Huang J, Tan H, Liu T, Shang C, Liu D, Guo L, Yao S - PLoS ONE (2015)

Bottom Line: 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.Our results suggest that Sema 3A may contribute to the regulation of aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Sun Yat-sen University, No. 58, the 2nd Zhongshan Road, Yuexiu District, Guangzhou city, Guangdong Province, 510080, China.

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.

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Comparison of total nerve fiber density and sympathetic nerve fiber density in deep infiltrating endometriotic specimens of uterosacral ligament and healthy uterosacral ligament.(A) Total nerve fibers were positively stained by Anti-PGP 9.5 antibody. Comparison of the total nerve fiber density (NFD, NF/mm2) of endometriosis-associated nerve of deep infiltrating endometriosis of uterosacral ligament (EAN-USL-EM), NFD of para-endometriotic nerve of deep infiltrating endometriosis of uterosacral ligament (PEN-USL-EM) and NFD of nerve of uterosacral ligament of control (N-USL-C). (B) Sympathetic nerve fibers were positively stained by Anti-TH antibody. Comparison of endometriosis-associated sympathetic NFD of USL-EM (ESAN-USL-EM), para-endometriotic sympathetic NFD of USL-EM (PESN-USL-EM) and sympathetic NFD of uterosacral ligament of control (SN-USL-C). *P<0.05.
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pone.0146027.g004: Comparison of total nerve fiber density and sympathetic nerve fiber density in deep infiltrating endometriotic specimens of uterosacral ligament and healthy uterosacral ligament.(A) Total nerve fibers were positively stained by Anti-PGP 9.5 antibody. Comparison of the total nerve fiber density (NFD, NF/mm2) of endometriosis-associated nerve of deep infiltrating endometriosis of uterosacral ligament (EAN-USL-EM), NFD of para-endometriotic nerve of deep infiltrating endometriosis of uterosacral ligament (PEN-USL-EM) and NFD of nerve of uterosacral ligament of control (N-USL-C). (B) Sympathetic nerve fibers were positively stained by Anti-TH antibody. Comparison of endometriosis-associated sympathetic NFD of USL-EM (ESAN-USL-EM), para-endometriotic sympathetic NFD of USL-EM (PESN-USL-EM) and sympathetic NFD of uterosacral ligament of control (SN-USL-C). *P<0.05.

Mentions: The NFD of Anti-PGP 9.5 (+) endometriosis-associated nerve of uterosacral ligament endometriosis (EAN-USL-EM) was significantly higher than NFD of para-endometriotic nerve of uterosacral ligament endometriosis (PEN-USL-EM) as well as NFD of nerve of uterosacral ligament of control (N-USL-C) (p<0.001, p<0.001, respectively) (Fig 4A, S5 Table). NFD of Anti-TH (+) endometriosis-associated sympathetic nerve of uterosacral ligament endometriosis (EASN-USL-EM) was also lower than NFD of para-endometriotic sympathetic nerve of uterosacral ligament endometriosis (PESN-USL-EM) (p<0.001). And NFD of PESN-USL-EM was also lower than that of sympathetic nerve of uterosacral ligament of control (SN-USL-C) (p = 0.012) (Fig 4B, S6 Table) (Fig 5).


Potential Role of Semaphorin 3A and Its Receptors in Regulating Aberrant Sympathetic Innervation in Peritoneal and Deep Infiltrating Endometriosis.

Liang Y, Wang W, Huang J, Tan H, Liu T, Shang C, Liu D, Guo L, Yao S - PLoS ONE (2015)

Comparison of total nerve fiber density and sympathetic nerve fiber density in deep infiltrating endometriotic specimens of uterosacral ligament and healthy uterosacral ligament.(A) Total nerve fibers were positively stained by Anti-PGP 9.5 antibody. Comparison of the total nerve fiber density (NFD, NF/mm2) of endometriosis-associated nerve of deep infiltrating endometriosis of uterosacral ligament (EAN-USL-EM), NFD of para-endometriotic nerve of deep infiltrating endometriosis of uterosacral ligament (PEN-USL-EM) and NFD of nerve of uterosacral ligament of control (N-USL-C). (B) Sympathetic nerve fibers were positively stained by Anti-TH antibody. Comparison of endometriosis-associated sympathetic NFD of USL-EM (ESAN-USL-EM), para-endometriotic sympathetic NFD of USL-EM (PESN-USL-EM) and sympathetic NFD of uterosacral ligament of control (SN-USL-C). *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4697795&req=5

pone.0146027.g004: Comparison of total nerve fiber density and sympathetic nerve fiber density in deep infiltrating endometriotic specimens of uterosacral ligament and healthy uterosacral ligament.(A) Total nerve fibers were positively stained by Anti-PGP 9.5 antibody. Comparison of the total nerve fiber density (NFD, NF/mm2) of endometriosis-associated nerve of deep infiltrating endometriosis of uterosacral ligament (EAN-USL-EM), NFD of para-endometriotic nerve of deep infiltrating endometriosis of uterosacral ligament (PEN-USL-EM) and NFD of nerve of uterosacral ligament of control (N-USL-C). (B) Sympathetic nerve fibers were positively stained by Anti-TH antibody. Comparison of endometriosis-associated sympathetic NFD of USL-EM (ESAN-USL-EM), para-endometriotic sympathetic NFD of USL-EM (PESN-USL-EM) and sympathetic NFD of uterosacral ligament of control (SN-USL-C). *P<0.05.
Mentions: The NFD of Anti-PGP 9.5 (+) endometriosis-associated nerve of uterosacral ligament endometriosis (EAN-USL-EM) was significantly higher than NFD of para-endometriotic nerve of uterosacral ligament endometriosis (PEN-USL-EM) as well as NFD of nerve of uterosacral ligament of control (N-USL-C) (p<0.001, p<0.001, respectively) (Fig 4A, S5 Table). NFD of Anti-TH (+) endometriosis-associated sympathetic nerve of uterosacral ligament endometriosis (EASN-USL-EM) was also lower than NFD of para-endometriotic sympathetic nerve of uterosacral ligament endometriosis (PESN-USL-EM) (p<0.001). And NFD of PESN-USL-EM was also lower than that of sympathetic nerve of uterosacral ligament of control (SN-USL-C) (p = 0.012) (Fig 4B, S6 Table) (Fig 5).

Bottom Line: 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.Our results suggest that Sema 3A may contribute to the regulation of aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Sun Yat-sen University, No. 58, the 2nd Zhongshan Road, Yuexiu District, Guangzhou city, Guangdong Province, 510080, China.

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.

Show MeSH
Related in: MedlinePlus