Transforming growth factor β signaling in uterine development and function

Journal of Animal Science and Biotechnology

Qinglei Li¹ 

[1] Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA

关键词: Uterus;    Transforming growth factor β;    Pregnancy;    Myometrium;    Implantation;    Embryonic development;    Development;    Decidualization;   

Others  :  1133490
DOI  :  10.1186/2049-1891-5-52

 received in 2014-07-09, accepted in 2014-10-28,  发布年份 2014

【 摘 要 】

Transforming growth factor β (TGFβ) superfamily is evolutionarily conserved and plays fundamental roles in cell growth and differentiation. Mounting evidence supports its important role in female reproduction and development. TGFBs1-3 are founding members of this growth factor family, however, the in vivo function of TGFβ signaling in the uterus remains poorly defined. By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus. The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.

【 授权许可】

   
2014 Li; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Massague J: Receptors for the TGF-beta family. Cell 1992, 69:1067-1070.
• [2]Massague J: TGF-beta signal transduction. Annu Rev Biochem 1998, 67:753-791.
• [3]Chang H, Brown CW, Matzuk MM: Genetic analysis of the mammalian transforming growth factor-β superfamily. Endocr Rev 2002, 23:787-823.
• [4]Schmierer B, Hill CS: TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol 2007, 8:970-982.
• [5]Tsukazaki T, Chiang TA, Davison AF, Attisano L, Wrana JL: SARA, a FYVE domain protein that recruits Smad2 to the TGF beta receptor. Cell 1998, 95:779-791.
• [6]Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, Miyazono K: Smad6 inhibits signalling by the TGF-beta superfamily. Nature 1997, 389:622-626.
• [7]Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke P: Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 1997, 389:631-635.
• [8]Massague J: How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000, 1:169-178.
• [9]Massague J: TGFbeta signalling in context. Nat Rev Mol Cell Biol 2012, 13:616-630.
• [10]Akhurst RJ, Hata A: Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discov 2012, 11:790-811.
• [11]Jonk LJC, Itoh S, Heldin CH, ten Dijke P, Kruijer W: Identification and functional characterization of a Smad binding element (SBE) in the JunB promoter that acts as a transforming growth factor-beta, activin, and bone morphogenetic protein-inducible enhancer. J Biol Chem 1998, 273:21145-21152.
• [12]Shi Y, Wang YF, Jayaraman L, Yang H, Massague J, Pavletich NP: Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling. Cell 1998, 94:585-594.
• [13]Ross S, Cheung E, Petrakis TG, Howell M, Kraus WL, Hill CS: Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription. Embo J 2006, 25:4490-4502.
• [14]Moustakas A, Heldin CH: Non-Smad TGF-beta signals. J Cell Sci 2005, 118:3573-3584.
• [15]Zhang YE: Non-Smad pathways in TGF-beta signaling. Cell Res 2009, 19:128-139.
• [16]Guo X, Wang XF: Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res 2009, 19:71-88.
• [17]Davis BN, Hilyard AC, Lagna G, Hata A: SMAD proteins control DROSHA-mediated microRNA maturation. Nature 2008, 454:56-61.
• [18]Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A: Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha. Mol Cell 2010, 39:373-384.
• [19]Davis-Dusenbery BN, Hata A: Smad-mediated miRNA processing: A critical role for a conserved RNA sequence. RNA Biol 2011, 8:71-76.
• [20]Attisano L, Wrana JL: Signal transduction by the TGF-beta superfamily. Science 2002, 296:1646-1647.
• [21]Derynck R, Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003, 425:577-584.
• [22]Yan X, Liu Z, Chen Y: Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai) 2009, 41:263-272.
• [23]Yan XH, Chen YG: Smad7: not only a regulator, but also a cross-talk mediator of TGF-beta signalling. Biochem J 2011, 434:1-10.
• [24]Pera EM, Ikeda A, Eivers E, De Robertis EM: Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev 2003, 17:3023-3028.
• [25]Wakefield LM, Hill CS: Beyond TGFbeta: roles of other TGFbeta superfamily members in cancer. Nat Rev Cancer 2013, 13:328-341.
• [26]Li Q, Graff JM, O’Connor AE, Loveland KL, Matzuk MM: SMAD3 regulates gonadal tumorigenesis. Mol Endocrinol 2007, 21:2472-2486.
• [27]Pangas SA, Li X, Umans L, Zwijsen A, Huylebroeck D, Gutierrez C, Wang D, Martin JF, Jamin SP, Behringer RR, Robertson EJ, Matzuk MM: Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol 2008, 28:248-257.
• [28]Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A: Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 1992, 360:313-319.
• [29]Edson MA, Nalam RL, Clementi C, Franco HL, Demayo FJ, Lyons KM, Pangas SA, Matzuk MM: Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development. Mol Endocrinol 2010, 24:1251-1266.
• [30]Middlebrook BS, Eldin K, Li X, Shivasankaran S, Pangas SA: Smad1-Smad5 ovarian conditional knockout mice develop a disease profile similar to the juvenile form of human granulosa cell tumors. Endocrinology 2009, 150:5208-5217.
• [31]Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, Ramirez F, Sakai LY, Dietz HC: Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 2003, 33:407-411.
• [32]Huang XR, Chung AC, Wang XJ, Lai KN, Lan HY: Mice overexpressing latent TGF-beta1 are protected against renal fibrosis in obstructive kidney disease. Am J Physiol Renal Physiol 2008, 295:F118-F127.
• [33]Massague J: TGFbeta in Cancer. Cell 2008, 134:215-230.
• [34]Arnold SJ, Maretto S, Islam A, Bikoff EK, Robertson EJ: Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. Dev Biol 2006, 296:104-118.
• [35]Huang Z, Wang DG, Ihida-Stansbury K, Jones PL, Martin JF: Defective pulmonary vascular remodeling in Smad8 mutant mice. Hum Mol Genet 2009, 18:2791-2801.
• [36]Tomic D, Miller KP, Kenny HA, Woodruff TK, Hoyer P, Flaws JA: Ovarian follicle development requires Smad3. Mol Endocrinol 2004, 18:2224-2240.
• [37]Gong X, McGee EA: Smad3 is required for normal follicular follicle-stimulating hormone responsiveness in the mouse. Biol Reprod 2009, 81:730-738.
• [38]Li Q, Pangas SA, Jorgez CJ, Graff JM, Weinstein M, Matzuk MM: Redundant roles of SMAD2 and SMAD3 in ovarian granulosa cells in vivo. Mol Cell Biol 2008, 28:7001-7011.
• [39]Pangas SA, Li X, Robertson EJ, Matzuk MM: Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice. Mol Endocrinol 2006, 20:1406-1422.
• [40]Li X, Tripurani SK, James R, Pangas SA: Minimal fertility defects in mice deficient in oocyte-expressed Smad4. Biol Reprod 2012, 86:1-6.
• [41]Quezada M, Wang J, Hoang V, McGee EA: Smad7 is a transforming growth factor-beta-inducible mediator of apoptosis in granulosa cells. Fertil Steril 2012, 97:1452-1459. e1451-1456
• [42]Gao Y, Wen H, Wang C, Li Q: SMAD7 antagonizes key TGFbeta superfamily signaling in mouse granulosa cells in vitro. Reproduction 2013, 146:1-11.
• [43]Li Q, Agno JE, Edson MA, Nagaraja AK, Nagashima T, Matzuk MM: Transforming growth factor beta receptor type 1 is essential for female reproductive tract integrity and function. PLoS Genet 2011, 7:e1002320.
• [44]Gao Y, Bayless KJ, Li Q: TGFBR1 is required for mouse myometrial development. Mol Endocrinol 2014, 28:380-394.
• [45]Clementi C, Tripurani SK, Large MJ, Edson MA, Creighton CJ, Hawkins SM, Kovanci E, Kaartinen V, Lydon JP, Pangas SA, DeMayo FJ, Matzuk MM: Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans. PLoS Genet 2013, 9:e1003863.
• [46]Nagashima T, Li Q, Clementi C, Lydon JP, Demayo FJ, Matzuk MM: BMPR2 is required for postimplantation uterine function and pregnancy maintenance. J Clin Invest 2013, 123:2539-2550.
• [47]Orvis GD, Behringer RR: Cellular mechanisms of Mullerian duct formation in the mouse. Dev Biol 2007, 306:493-504.
• [48]Brody JR, Cunha GR: Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: I. Normal development. Am J Anat 1989, 186:1-20.
• [49]Brody JR, Cunha GR: Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: II. Effects of DES on development. Am J Anat 1989, 186:21-42.
• [50]Miller C, Sassoon DA: Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract. Development 1998, 125:3201-3211.
• [51]Wang Y, Jia Y, Franken P, Smits R, Ewing PC, Lydon JP, Demayo FJ, Burger CW, Anton Grootegoed J, Fodde R, Blok LJ: Loss of APC function in mesenchymal cells surrounding the Mullerian duct leads to myometrial defects in adult mice. Mol Cell Endocrinol 2011, 341:48-54.
• [52]Arango NA, Szotek PP, Manganaro TF, Oliva E, Donahoe PK, Teixeira J: Conditional deletion of beta-catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium. Dev Biol 2005, 288:276-283.
• [53]Parr BA, McMahon AP: Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a. Nature 1998, 395:707-710.
• [54]Mesiano S, Chan EC, Fitter JT, Kwek K, Yeo G, Smith R: Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium. J Clin Endocrinol Metab 2002, 87:2924-2930.
• [55]Condon JC, Jeyasuria P, Faust JM, Wilson JW, Mendelson CR: A decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition. Proc Natl Acad Sci U S A 2003, 100:9518-9523.
• [56]Brainard AM, Miller AJ, Martens JR, England SK: Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K + current. Am J Physiol Cell Physiol 2005, 289:C49-C57.
• [57]Brainard AM, Korovkina VP, England SK: Potassium channels and uterine function. Semin Cell Dev Biol 2007, 18:332-339.
• [58]Pierce SL, Kresowik JD, Lamping KG, England SK: Overexpression of SK3 channels dampens uterine contractility to prevent preterm labor in mice. Bio Reprod 2008, 78:1058-1063.
• [59]Pierce SL, England SK: SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of the KCNN3 gene. Am J Physiol Endocrinol Metab 2010, 299:E640-E646.
• [60]Yallampalli C, Dong YL: Estradiol-17beta inhibits nitric oxide synthase (NOS)-II and stimulates NOS-III gene expression in the rat uterus. Bio Reprod 2000, 63:34-41.
• [61]Yallampalli C, Garfield RE, Byam-Smith M: Nitric oxide inhibits uterine contractility during pregnancy but not during delivery. Endocrinology 1993, 133:1899-1902.
• [62]Yallampalli C, Izumi H, Byam-Smith M, Garfield RE: An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy. Am J Obstet Gynecol 1994, 170:175-185.
• [63]Dong YL, Yallampalli C: Interaction between nitric oxide and prostaglandin E2 pathways in pregnant rat uteri. Am J Physiol 1996, 270:E471-E476.
• [64]Tong D, Lu X, Wang HX, Plante I, Lui E, Laird DW, Bai D, Kidder GM: A dominant loss-of-function GJA1 (Cx43) mutant impairs parturition in the mouse. Biol Reprod 2009, 80:1099-1106.
• [65]Renthal NE, Chen CC, Williams KC, Gerard RD, Prange-Kiel J, Mendelson CR: miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc Natl Acad Sci U S A 2010, 107:20828-20833.
• [66]Williams KC, Renthal NE, Gerard RD, Mendelson CR: The microRNA (miR)-199a/214 cluster mediates opposing effects of progesterone and estrogen on uterine contractility during pregnancy and labor. Mol Endocrinol 2012, 26:1857-1867.
• [67]Cockburn K, Rossant J: Making the blastocyst: lessons from the mouse. J Clin Invest 2010, 120:995-1003.
• [68]Flach G, Johnson MH, Braude PR, Taylor RA, Bolton VN: The transition from maternal to embryonic control in the 2-cell mouse embryo. Embo J 1982, 1:681-686.
• [69]Salamonsen LA, Dimitriadis E, Jones RL, Nie G: Complex regulation of decidualization: a role for cytokines and proteases--a review. Placenta 2003, 24(Suppl A):S76-S85.
• [70]Wang H, Dey SK: Roadmap to embryo implantation: clues from mouse models. Nat Rev Genet 2006, 7:185-199.
• [71]Cha J, Sun X, Dey SK: Mechanisms of implantation: strategies for successful pregnancy. Nat Med 2012, 18:1754-1767.
• [72]Guzelogiu-Kayisli Z, Kayisli UA, Taylor HS: The role of growth factors and cytokines during implantation: endocrine and paracrine interactions. Semin Reprod Med 2009, 27:62-79.
• [73]Memon MA, Anway MD, Covert TR, Uzumcu M, Skinner MK: Transforming growth factor beta (TGF beta 1, TGF beta 2 and TGF beta 3) null-mutant phenotypes in embryonic gonadal development. Mol Cell Endocrinol 2008, 294:70-80.
• [74]Mu Z, Yang Z, Yu D, Zhao Z, Munger JS: TGFbeta1 and TGFbeta3 are partially redundant effectors in brain vascular morphogenesis. Mech Dev 2008, 125:508-516.
• [75]Kallapur S, Ormsby I, Doetschman T: Strain dependency of TGFbeta1 function during embryogenesis. Mol Reprod Dev 1999, 52:341-349.
• [76]Ingman WV, Robker RL, Woittiez K, Robertson SA: Null mutation in transforming growth factor beta1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest. Endocrinology 2006, 147:835-845.
• [77]Paria BC, Dey SK: Preimplantation embryo development in vitro - cooperative interactions among embryos and role of growth-factors. Proc Natl Acad Sci U S A 1990, 87:4756-4760.
• [78]Lim J, Bongso A, Ratnam S: Mitogenic and cytogenetic evaluation of transforming growth-factor-beta on murine preimplantation embryonic-development in-vitro. Mol Reprod Dev 1993, 36:482-487.
• [79]Nowak RA, Haimovici F, Biggers JD, Erbach GT: Transforming growth factor-beta stimulates mouse blastocyst outgrowth through a mechanism involving parathyroid hormone-related protein. Biol Reprod 1999, 60:85-93.
• [80]Feinberg RF, Kliman HJ, Wang CL: Transforming growth factor-beta stimulates trophoblast oncofetal fibronectin synthesis in vitro: implications for trophoblast implantation in vivo. J Clin Endocrinol Metab 1994, 78:1241-1248.
• [81]Graham CH, Connelly I, Macdougall JR, Kerbel RS, Stetlerstevenson WG, Lala PK: Resistance of malignant trophoblast cells to both the antiproliferative and anti-invasive effects of transforming growth-factor-beta. Exp Cell Res 1994, 214:93-99.
• [82]Letterio JJ, Geiser AG, Kulkarni AB, Roche NS, Sporn MB, Roberts AB: Maternal rescue of transforming growth factor-beta 1 null mice. Science 1994, 264:1936-1938.
• [83]McLennan IS, Koishi K: Fetal and maternal transforming growth factor-beta 1 may combine to maintain pregnancy in mice. Biol Reprod 2004, 70:1614-1618.
• [84]Akinyemi BO, Adewoye BR, Fakoya TA: Uterine fibroid: a review. Niger J Med 2004, 13:318-329.
• [85]Dou Q, Zhao Y, Tarnuzzer RW, Rong H, Williams RS, Schultz GS, Chegini N: Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin-releasing hormone agonist therapy. J Clin Endocrinol Metab 1996, 81:3222-3230.
• [86]Arici A, Sozen I: Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertil Steril 2000, 73:1006-1011.
• [87]Levy G, Malik M, Britten J, Gilden M, Segars J, Catherino WH: Liarozole inhibits transforming growth factor-beta3-mediated extracellular matrix formation in human three-dimensional leiomyoma cultures. Fertil Steril 2014, 102:272-281.
• [88]Joseph DS, Malik M, Nurudeen S, Catherino WH: Myometrial cells undergo fibrotic transformation under the influence of transforming growth factor beta-3. Fertil Steril 2010, 93:1500-1508.
• [89]Malik M, Catherino WH: Development and validation of a three-dimensional in vitro model for uterine leiomyoma and patient-matched myometrium. Fertil Steril 2012, 97:1287-1293.
• [90]Malik M, Catherino WH: Novel method to characterize primary cultures of leiomyoma and myometrium with the use of confirmatory biomarker gene arrays. Fertil Steril 2007, 87:1166-1172.
• [91]Luo X, Ding L, Chegini N: CCNs, fibulin-1C and S100A4 expression in leiomyoma and myometrium: inverse association with TGF-beta and regulation by TGF-beta in leiomyoma and myometrial smooth muscle cells. Mol Hum Reprod 2006, 12:245-256.
• [92]Levens E, Luo X, Ding L, Williams RS, Chegini N: Fibromodulin is expressed in leiomyoma and myometrium and regulated by gonadotropin-releasing hormone analogue therapy and TGF-beta through Smad and MAPK-mediated signalling. Mol Hum Reprod 2005, 11:489-494.
• [93]Norian JM, Malik M, Parker CY, Joseph D, Leppert PC, Segars JH, Catherino WH: Transforming growth factor beta3 regulates the versican variants in the extracellular matrix-rich uterine leiomyomas. Reprod Sci 2009, 16:1153-1164.
• [94]Di X, Andrews DM, Tucker CJ, Yu L, Moore AB, Zheng X, Castro L, Hermon T, Xiao H, Dixon D: A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med 2012, 44:281-292.
• [95]Li Z, Burzawa JK, Troung A, Feng S, Agoulnik IU, Tong X, Anderson ML, Kovanci E, Rajkovic A, Agoulnik AI: Relaxin signaling in uterine fibroids. Ann N Y Acad Sci 2009, 1160:374-378.
• [96]Grudzien MM, Low PS, Manning PC, Arredondo M, Belton RJ Jr, Nowak RA: The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells. Fertil Steril 2010, 93:1290-1298.
• [97]Ohara N, Morikawa A, Chen W, Wang J, DeManno DA, Chwalisz K, Maruo T: Comparative effects of SPRM asoprisnil (J867) on proliferation, apoptosis, and the expression of growth factors in cultured uterine leiomyoma cells and normal myometrial cells. Reprod Sci 2007, 14:20-27.
• [98]De Falco M, Staibano S, D’Armiento FP, Mascolo M, Salvatore G, Busiello A, Carbone IF, Pollio F, Di Lieto A: Preoperative treatment of uterine leiomyomas: Clinical findings and expression of transforming growth factor-beta 3 and connective tissue growth factor. J Soc Gynecol Investig 2006, 13:297-303.
• [99]Sinclair DC, Mastroyannis A, Taylor HS: Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and anticoagulant expression through secretion of TGF-beta 3. J Clin Endocr Metab 2011, 96:412-421.
• [100]Peracoli MT, Menegon FT, Borges VT, de Araujo Costa RA, Thomazini-Santos IA, Peracoli JC: Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia. J Reprod Immunol 2008, 79:79-84.
• [101]Djurovic S, Schjetlein R, Wisloff F, Haugen G, Husby H, Berg K: Plasma concentrations of Lp(a) lipoprotein and TGF-beta1 are altered in preeclampsia. Clin Genet 1997, 52:371-376.
• [102]Enquobahrie DA, Williams MA, Qiu C, Woelk GB, Mahomed K: Maternal plasma transforming growth factor-beta1 concentrations in preeclamptic and normotensive pregnant Zimbabwean women. J Matern Fetal Neona 2005, 17:343-348.
• [103]Wang XJ, Zhou ZY, Xu YJ: Changes of plasma uPA and TGF-beta1 in patients with preeclampsia. Sichuan Da Xue Xue Bao Yi Xue Ban 2010, 41:118-120.
• [104]Feizollahzadeh S, Taheripanah R, Khani M, Farokhi B, Amani D: Promoter region polymorphisms in the transforming growth factor beta-1 (TGFbeta1) gene and serum TGFbeta1 concentration in preeclamptic and control Iranian women. J Reprod Immunol 2012, 94:216-221.
• [105]Shaarawy M, El Meleigy M, Rasheed K: Maternal serum transforming growth factor beta-2 in preeclampsia and eclampsia, a potential biomarker for the assessment of disease severity and fetal outcome. J Soc Gynecol Investig 2001, 8:27-31.
• [106]Caniggia I, Grisaru-Gravnosky S, Kuliszewsky M, Post M, Lye SJ: Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest 1999, 103:1641-1650.
• [107]Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, Bdolah Y, Lim KH, Yuan HT, Libermann TA, Stillman IE, Roberts D, D’Amore PA, Epstein FH, Sellke FW, Romero R, Sukhatme VP, Letarte M, Karumanchi SA: Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006, 12:642-649.
• [108]Stepan H, Kramer T, Faber R: Maternal plasma concentrations of soluble endoglin in pregnancies with intrauterine growth restriction. J Clin Endocrinol Metab 2007, 92:2831-2834.
• [109]Lyall F, Simpson H, Bulmer JN, Barber A, Robson SC: Transforming growth factor-beta expression in human placenta and placental bed in third trimester normal pregnancy, preeclampsia, and fetal growth restriction. Am J Pathol 2001, 159:1827-1838.
• [110]Szarka A, Rigo J Jr, Lazar L, Beko G, Molvarec A: Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol 2010, 11:59. BioMed Central Full Text
• [111]Perucci LO, Gomes KB, Freitas LG, Godoi LC, Alpoim PN, Pinheiro MB, Miranda AS, Teixeira AL, Dusse LM, Sousa LP: Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia. PLoS One 2014, 9:e97632.
• [112]Huber A, Hefler L, Tempfer C, Zeisler H, Lebrecht A, Husslein P: Transforming growth factor-beta 1 serum levels in pregnancy and pre-eclampsia. Acta Obstet Gynecol Scand 2002, 81:168-171.
• [113]Bersinger NA, Smarason AK, Muttukrishna S, Groome NP, Redman CW: Women with preeclampsia have increased serum levels of pregnancy-associated plasma protein a (PAPP-A), inhibin A, activin A, and soluble E-selectin. Hypertens Pregnancy 2003, 22:45-55.
• [114]Silver HM, Lambert-Messerlian GM, Reis FM, Diblasio AM, Petraglia F, Canick JA: Mechanism of increased maternal serum total activin A and inhibin A in preeclampsia. J Soc Gynecol Investig 2002, 9:308-312.
• [115]Yair D, Eshed-Englender T, Kupferminc MJ, Geva E, Frenkel J, Sherman D: Serum levels of inhibin B, unlike inhibin A and activin A, are not altered in women with preeclampsia. Am J Reprod Immunol 2001, 45:180-187.
• [116]Laivuori H, Kaaja R, Turpeinen U, Stenman UH, Ylikorkala O: Serum activin A and inhibin A elevated in pre-eclampsia: no relation to insulin sensitivity. BJOG 1999, 106:1298-1303.
• [117]Figueras F, Gardosi J: Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynecol 2011, 204:288-300.
• [118]Ostlund E, Tally M, Fried G: Transforming growth factor-beta1 in fetal serum correlates with insulin-like growth factor-I and fetal growth. Obstet Gynecol 2002, 100:567-573.
• [119]Sanford LP, Ormsby I, GittenbergerdeGroot AC, Sariola H, Friedman R, Boivin GP, Cardell EL, Doetschman T: TGF beta 2 knockout mice have multiple developmental defects that are nonoverlapping with other TGF beta knockout phenotypes. Development 1997, 124:2659-2670.
• [120]Jeyabalan A, McGonigal S, Gilmour C, Hubel CA, Rajakumar A: Circulating and placental endoglin concentrations in pregnancies complicated by intrauterine growth restriction and preeclampsia. Placenta 2008, 29:555-563.
• [121]Yinon Y, Nevo O, Xu J, Many A, Rolfo A, Todros T, Post M, Caniggia I: Severe intrauterine growth restriction pregnancies have increased placental endoglin levels: hypoxic regulation via transforming growth factor-beta 3. Am J Pathol 2008, 172:77-85.
• [122]Park CB, DeMayo FJ, Lydon JP, Dufort D: NODAL in the uterus is necessary for proper placental development and maintenance of pregnancy. Biol Reprod 2012, 86:194.
• [123]Mills AM, Longacre TA: Endometrial hyperplasia. Semin Diagn Pathol 2010, 27:199-214.
• [124]Kurman RJ, Kaminski PF, Norris HJ: The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer 1985, 56:403-412.
• [125]Montgomery BE, Daum GS, Dunton CJ: Endometrial hyperplasia: a review. Obstet Gynecol Surv 2004, 59:368-378.
• [126]Shutter J, Wright TC: Prevalence of underlying adenocarcinoma in women with atypical endometrial hyperplasia. Int J Gynecol Pathol 2005, 24:313-318.
• [127]Lacey JV, Chia VM: Endometrial hyperplasia and the risk of progression to carcinoma. Maturitas 2009, 63:39-44.
• [128]Hahn HS, Chun YK, Kwon YI, Kim TJ, Lee KH, Shim JU, Mok JE, Lim KT: Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia. Eur J Obstet Gynecol Reprod Biol 2010, 150:80-83.
• [129]Gambrell RD: Progestogens in estrogen-replacement therapy. Clin Obstet Gynecol 1995, 38:890-901.
• [130]Reed SD, Voigt LF, Newton KM, Garcia RH, Allison HK, Epplein M, Jordan D, Swisher E, Weiss NS: Progestin therapy of complex endometrial hyperplasia with and without atypia. Obstet Gynecol 2009, 113:655-662.
• [131]Stambolic V, Tsao MS, Macpherson D, Suzuki A, Chapman WR, Mak TW: High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten(+/−) mice. Cancer Res 2000, 60:3605-3611.
• [132]Milam MR, Soliman PT, Chung LH, Schmeler KM, Bassett RL, Broaddus RR, Lu KH: Loss of phosphatase and tensin homologue deleted on chromosome 10 and phosphorylation of mammalian target of rapamycin are associated with progesterone refractory endometrial hyperplasia. Int J Gynecol Cancer 2008, 18:146-151.
• [133]Parekh TV, Gama P, Wen X, Demopoulos R, Munger JS, Carcangiu ML, Reiss M, Gold LI: Transforming growth factor beta signaling is disabled early in human endometrial carcinogenesis concomitant with loss of growth inhibition. Cancer Res 2002, 62:2778-2790.
• [134]Lecanda J, Parekh TV, Gama P, Lin K, Liarski V, Uretsky S, Mittal K, Gold LI: Transforming growth factor-beta, estrogen, and progesterone converge on the regulation of p27Kip1 in the normal and malignant endometrium. Cancer Res 2007, 67:1007-1018.
• [135]Piestrzeniewicz-Ulanska D, McGuinness D, Yeaman G: TGF-β Signaling in Endometrial Cancer. In Transforming Growth Factor-β in Cancer Therapy, Volume II. Edited by Jakowlew S. Totowa, NJ: Humana Press; 2008:63-78.
• [136]Gao Y, Li S, Li Q: Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model. Mol Hum Reprod 2014, 20:776-786.