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Paratubal Cyst Size Correlates With Obesity and Dysregulation of the Wnt Signaling Pathway

Published:April 26, 2017DOI:https://doi.org/10.1016/j.jpag.2017.04.002

      Abstract

      Study Objective

      Paratubal cysts (PTCs) occur in 7%-10% of women, regardless of age. Although common, PTCs often are found incidentally because of the potential for these cysts to be asymptomatic. The specific aims of the study were to determine if PTC number and size correlated with signs of hyperandrogenism and obesity, as well as to investigate the molecular profiles of these PTCs in samples derived from female adolescents.

      Design, Setting, Participants, Interventions, and Main Outcome Measures

      A prospective cohort study was performed in a single children's hospital. Girls 18 years of age or younger who underwent surgery for PTC suspected on the basis of the presence of a persistent adnexal cyst on imaging or a concern for adnexal torsion involving a cyst were consented to participate in the study.

      Results

      Nineteen patients met enrollment criteria with a mean age at menarche of 11.2 ± 1.3 years. Most of the patients (84%; n = 16/19) had adnexal torsion at the time of diagnosis of PTC. Irregular menses and hirsutism was found in 52.6% (n = 10/19) of the patients, among whom 36.8% (n = 7/19) were obese. The mean PTC size was 10.4 ± 4.3 cm with 57.9% (n = 11/19) of the cohort having more than 1 PTC. When patients were compared on the basis of their body mass index, the size of PTCs was significantly larger in the overweight/obese group. The wingless-type (WNT) signaling members catenin beta 1 (CTNBB1) and wingless-type MMTV integration site family, member 7A (WNT7A) were upregulated in 86% (n = 12/14) and 79% (n = 11/14) of the patients, respectively. WNT7A was significantly upregulated in girls with 1 cyst and low body mass index.

      Conclusion

      A correlation exists between obesity, cyst size, and hyperandrogenism. Activation of the WNT/CTNBB1 pathway via WNT7A might play a role in PTC development.

      Key Words

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      References

        • Muolokwu E.
        • Sanchez J.
        • Bercaw J.L.
        • et al.
        The incidence and surgical management of paratubal cysts in a pediatric and adolescent population.
        J Pediatr Surg. 2011; 46: 2161-2163
        • Drews U.
        Helper function of the Wolffian ducts and role of androgens in the development of the vagina.
        Sex Dev. 2007; 1: 100
        • Bentvelsen F.M.
        • Brinkmann A.O.
        • van der Schoot P.
        • et al.
        Developmental pattern and regulation by androgens of androgen receptor expression in the urogenital tract of the rat.
        Mol Cell Endocrinol. 1995; 113: 245
        • Kobayashi A.
        • Behringer R.R.
        Developmental genetics of the female reproductive tract in mammals.
        Nat Rev Genet. 2003; 4: 969
        • Welsh M.
        • Sharpe R.M.
        • Walker M.
        • Smith L.B.
        • Saunders P.T.
        New insights into the role of androgens in Wolffian duct stabilization in male and female rodents.
        Endocrinology. 2009; 150: 2472
        • Kiseli M.
        • Caglar G.S.
        • Cengiz S.D.
        • Karadag D.
        • Yilmaz M.B.
        Clinical diagnosis and complications of paratubal cysts: review of the literature and report of uncommon presentations.
        Arch Gynecol Obstet. 2012; 285: 1563
        • Lee S.
        • Ahn K.H.
        • Park H.T.
        • et al.
        Paratubal borderline malignancy: a case of a 17-year-old adolescent female treated with laparo-endoscopic single-site surgery and a review of the literature.
        J Pediatr Adolesc Gynecol. 2016; 29: 74
        • Devouassoux-Shisheboran M.
        • Silver S.A.
        • Tavassoli F.A.
        Wolffian adnexal tumor, so-called female adnexal tumor of probable Wolffian origin (FATWO): immunohistochemical evidence in support of a Wolffian origin.
        Hum Pathol. 1999; 30: 856
        • Nagaraja A.K.
        • Andreu-Vieyra C.
        • Franco H.L.
        • et al.
        Deletion of Dicer in somatic cells of the female reproductive tract causes sterility.
        Mol Endocrinol. 2008; 22: 2336
        • Muolokwu E.
        • Sanchez J.
        • Bercaw J.L.
        • et al.
        Paratubal cysts, obesity, and hyperandrogenism.
        J Pediatr Surg. 2011; 46: 2164
        • Legro R.S.
        • Lin H.M.
        • Demers L.M.
        • Lloyd T.
        Rapid maturation of the reproductive axis during perimenarche independent of body composition.
        J Clin Endocrinol Metab. 2000; 85: 1021
        • Carmina E.
        • Oberfield S.E.
        • Lobo R.A.
        The diagnosis of polycystic ovary syndrome in adolescents.
        Am J Obstet Gynecol. 2010; 203: 201.e1
        • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
        Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
        Fertil Steril. 2004; 81: 19
        • Liou T.H.
        • Yang J.H.
        • Hsieh C.H.
        • Lee C.Y.
        • Hsu C.S.
        • Hsu M.I.
        Clinical and biochemical presentations of polycystic ovary syndrome among obese and nonobese women.
        Fertil Steril. 2009; 92: 1960
        • Tanwar P.S.
        • Kaneko-Tarui T.
        • Zhang L.
        • Tanaka Y.
        • Crum C.P.
        • Teixeira J.M.
        Stromal liver kinase B1 [STK11] signaling loss induces oviductal adenomas and endometrial cancer by activating mammalian Target of Rapamycin Complex 1.
        PLoS Genet. 2012; 8: e1002906
        • Murphy D.B.
        • Seemann S.
        • Wiese S.
        • Kirschner R.
        • Grzeschik K.H.
        • Thies U.
        The human hepatocyte nuclear factor 3/fork head gene FKHL13: genomic structure and pattern of expression.
        Genomics. 1997; 40: 462
        • Camoretti-Mercado B.
        • Forsythe S.M.
        • LeBeau M.M.
        • et al.
        Expression and cytogenetic localization of the human SM22 gene (TAGLN).
        Genomics. 1998; 49: 452
        • Noack F.
        • Schmidt H.
        • Buchweitz O.
        • Malik E.
        • Horny H.P.
        Genomic imbalance and onco-protein expression of ovarian endometrioid adenocarcinoma arisen in an endometriotic cyst.
        Anticancer Res. 2004; 24: 151
        • Quartuccio S.M.
        • Lantvit D.D.
        • Bosland M.C.
        • Burdette J.E.
        Conditional inactivation of p53 in mouse ovarian surface epithelium does not alter MIS driven Smad2-dominant negative epithelium-lined inclusion cysts or teratomas.
        PLoS One. 2013; 8: e65067
        • Himes J.H.
        Examining the evidence for recent secular changes in the timing of puberty in US children in light of increases in the prevalence of obesity.
        Mol Cell Endocrinol. 2006; 254-255: 13
        • Jamin S.P.
        • Arango N.A.
        • Mishina Y.
        • Hanks M.C.
        • Behringer R.R.
        Requirement of Bmpr1a for Mullerian duct regression during male sexual development.
        Nat Genet. 2002; 32: 408
        • Moren A.
        • Raja E.
        • Heldin C.H.
        • Moustakas A.
        Negative regulation of TGFbeta signaling by the kinase LKB1 and the scaffolding protein LIP1.
        J Biol Chem. 2011; 286: 341
        • Wynn T.A.
        Cellular and molecular mechanisms of fibrosis.
        J Pathol. 2008; 214: 199
        • Kumar M.
        • Syed S.M.
        • Taketo M.M.
        • Tanwar P.S.
        Epithelial Wnt/beta-catenin signalling is essential for epididymal coiling.
        Dev Biol. 2016; 412: 234
        • MacDonald B.T.
        • Tamai K.
        • He X.
        Wnt/beta-catenin signaling: components, mechanisms, and diseases.
        Dev Cell. 2009; 17: 9
        • Carmon K.S.
        • Loose D.S.
        Secreted frizzled-related protein 4 regulates two Wnt7a signaling pathways and inhibits proliferation in endometrial cancer cells.
        Mol Cancer Res. 2008; 6: 1017
        • Kobayashi A.
        • Stewart C.A.
        • Wang Y.
        • et al.
        β-Catenin is essential for Mullerian duct regression during male sexual differentiation.
        Development. 2011; 138: 1967
        • Boyer A.
        • Yeh J.R.
        • Zhang X.
        • et al.
        CTNNB1 signaling in sertoli cells downregulates spermatogonial stem cell activity via WNT4.
        PLoS One. 2012; 7: e29764
        • Davis E.K.
        • Zou Y.
        • Ghosh A.
        Wnts acting through canonical and noncanonical signaling pathways exert opposite effects on hippocampal synapse formation.
        Neural Dev. 2008; 3: 32
        • Miller C.
        • Sassoon D.A.
        Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract.
        Development. 1998; 125: 3201
        • Parr B.A.
        • McMahon A.P.
        Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a.
        Nature. 1998; 395: 707
        • Heikkila M.
        • Peltoketo H.
        • Vainio S.
        Wnts and the female reproductive system.
        J Exp Zool. 2001; 290: 616
        • Marose T.D.
        • Merkel C.E.
        • McMahon A.P.
        • Carroll T.J.
        Beta-catenin is necessary to keep cells of ureteric bud/Wolffian duct epithelium in a precursor state.
        Dev Biol. 2008; 314: 112
        • Stewart C.A.
        • Wang Y.
        • Bonilla-Claudio M.
        • et al.
        CTNNB1 in mesenchyme regulates epithelial cell differentiation during Mullerian duct and postnatal uterine development.
        Mol Endocrinol. 2013; 27: 1442
        • Deutscher E.
        • Hung-Chang Yao H.
        Essential roles of mesenchyme-derived beta-catenin in mouse Mullerian duct morphogenesis.
        Dev Biol. 2007; 307: 227
        • Funa N.S.
        • Schachter K.A.
        • Lerdrup M.
        • et al.
        beta-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4.
        Cell Stem Cell. 2015; 16: 639
        • van der Horst P.H.
        • van der Zee M.
        • Heijmans-Antonissen C.
        • et al.
        A mouse model for endometrioid ovarian cancer arising from the distal oviduct.
        Int J Cancer. 2014; 135: 1028
        • Zhang X.L.
        • Peng C.J.
        • Peng J.
        • Jiang L.Y.
        • Ning X.M.
        • Zheng J.H.
        Prognostic role of Wnt7a expression in ovarian carcinoma patients.
        Neoplasma. 2010; 57: 545
        • Yoshioka S.
        • King M.L.
        • Ran S.
        • et al.
        WNT7A regulates tumor growth and progression in ovarian cancer through the WNT/beta-catenin pathway.
        Mol Cancer Res. 2012; 10: 469
        • Dixon S.C.
        • Nagle C.M.
        • Thrift A.P.
        • et al.
        Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study.
        Int J Epidemiol. 2016; 45: 884