子宮與下泌尿道 (LUT) 之間的交互作用是下泌尿道功能障礙與骨盆腔疼痛症候群高度併發的重要影響，然而，子宮異位症患者的高度循環性腺類固醇是否會影響子宮－尿道交互作用 (UUC) 還尚未清楚。目前的研究證實了子宮－尿道交互作用在子宮內膜異位症的條件下是雌激素依賴性敏化。在本實驗中，子宮內膜異位症 (EM) 和naïve組動物透過子宮組織與脂肪組織的自體移植來誘導。以測定急性子宮刺激的骨盆－尿道反射來反映出子宮－尿道交互作用。與naïve組的動物相比，EM組的動物顯示出增強的UUC，然而這種增強的UUC能夠被α亞型雌激素受體的藥理拮抗所逆轉。此外，混合譜系白血病1 (MLL1) 和 Trp-Asp repeat domain 5 subunit (WDR5) 之間的相互作用以及之後的H3K4me3-dependent spinal mGluR5 轉錄之間的可能存在著潛在參與。目前為止，我們的數據顯示出UUC在EM的動物模式中以雌激素依賴性的方式敏化。

The crosstalk between the uterus and the lower urinary tract (LUT) underlies the high concurrence of LUT dysfunctions with the pelvic pain syndrome, nevertheless, if high circulatory gonadal steroids in endometriosis patients could impact the uterus-urethra crosstalk (UUC) is unclear. The current study tested the hypothesis that the UUC was estrogen-dependently sensitized under the endometriosis condition. Endometriosis-like (EM) and naïve animals were induced by auto-grafting of uterine tissue and adipose tissue, respectively. The pelvic-urethral reflex in response to acute uterine irritation was assay to reflect the UUC. When compared with their naïve littermates, EM animals display enhanced UUC that was reversed by pharmacological antagonizing of alpha-subtype estrogen receptors. Moreover, the potential involvement of the interaction between the mixed lineage leukemia 1 (MLL1) and Trp-Asp repeat domain 5 subunit (WDR5) and the subsequently H3K4me3-dependent spinal mGluR5 transcription is suspected. So far, our data reveal UUC was sensitized in EM animal in an estrogen-dependent manner.

Onofrio Triolo, Antonio Simone Laganà, Emanuele Sturlese.Endometriosis: An Overview. J Clin Med Res. 2013; 5(3): 153–163.
AlexisLaux-Biehlmann, Thomasd’Hooghe, Thomas M.Zollner. Menstruation pulls the trigger for inflammation and pain in endometriosis. Trends inPharmacological Sciences.2015;36(5): 270-276.
Goodman HM, Kredentser D, Deligdisch L. Postmenopausal endometriosis associated with hormone replacement therapy. A case report. J Reprod Med. 1989;34:231–233.
Takayama K, Zeitoun K, Gunby RT, Sasano H, Carr BR, Bulun SE. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril. 1998;69:709–713.
Peng HY, Chen GD, Lai CY, Hsieh MC, Hsu HH, Wu HC, Lin TB. PI3K modulates estrogen‐dependent facilitation of colon‐to‐urethra cross‐organ reflex sensitization in ovariectomized female rats. J Neurochem. 2010b; 113:54-66.
William C.de Groat. Anatomy and physiology of the lower urinary tract.Urologic Clinics of North America. 1993; 20: 383-401.
Peng HY, Chen GD, Tung KC, Lai CY, Hsien MC, Chiu CH, Lu HT, Liao JM, Lee SD, Lin TB. Colon mustard oil instillation induced cross-organ reflex sensitization on the pelvic–urethra reflex activity in rats. Pain. 2009c; 142:75-88.
Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011 17(3):327-46.
Kim JH, Han E. Endometriosis and Female Pelvic Pain. Semin Reprod Med. 2018 Mar;36(2):143-151.
Tawadros C, Burnett K, Derbyshire LF, Tawadros T, Clarke NW, Betts CD. External urethral sphincter electromyography in asymptomatic women and the influence of the menstrual cycle. BJU Int. 2015 Sep;116(3):423-31.
Lin TB, Lai CY, Hsieh MC, Ho YC, Wang HH, Yang PS, Cheng JK, Chen GD, Ng SC, Peng HY. Inhibiting MLL1-WDR5 interaction ameliorates neuropathic allodynia by attenuating histone H3 lysine 4 trimethylation-dependent spinal mGluR5 transcription. Pain. 2020 Sep 1;161(9):1995-2009.
Maddern J, Grundy L, Castro J, Brierley SM. Pain in Endometriosis. Front Cell Neurosci. 2020 Oct 6;14:590823.
Li T, Mamillapalli R, Ding S, Chang H, Liu ZW, Gao XB, Taylor HS. Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice. Biol Reprod. 2018 Aug 1;99(2):349-359.
Marquardt RM, Kim TH, Shin JH, Jeong JW. Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis? Int J Mol Sci. 2019 Aug 5;20(15):3822.
Guimaraes MZP, Jordt SE. TRPA1 : A Sensory Channel of Many Talents. In: Liedtke WB, Heller S, editors. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 11.
Peng HY, Yeh CM, Cheng JK, Chau YP, Ruan T, Chen GD, Hsieh MC, Lai CY, Lin TB. Acute uterine irritation provokes colonic motility via transient receptor potential A(1)-dependent spinal NR2B phosphorylation in rats. Anesthesiology. 2014 Feb;120(2):436-46.