Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways

 

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Abstract

Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease.

• References

• 1 Adamson GD, Kennedy SH, Hummelshoj L. Creating solutions in endometriosis: global collaboration through the World Endometriosis Research Foundation. J Endometriosis 2010; 2: 3-6
  PubMedGoogle Scholar
• 2 Simoens S, Dunselman G, Dirksen C , et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod 2012; 27 (5) 1292-1299
  CrossrefPubMedGoogle Scholar
• 3 De Graaff AA, D'Hooghe TM, Dunselman GA, Dirksen CD, Hummelshoj L, Simoens S. WERF EndoCost Consortium. The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod 2013; 28 (10) 2677-2685
  CrossrefPubMedGoogle Scholar
• 4 Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001; 75 (1) 1-10
  CrossrefPubMedGoogle Scholar
• 5 Sidell N, Han SW, Parthasarathy S. Regulation and modulation of abnormal immune responses in endometriosis. Ann N Y Acad Sci 2002; 955: 159-173 ; discussion 199–200, 396–406
  CrossrefPubMedGoogle Scholar
• 6 Taylor RN. Classical and neo-classical concepts in the etiology of endometriosis. In: Hedon B, Mettler L, Tinneberg H-R, , eds. Proceedings of the IFFS 20th World Congress on Fertility and Sterility. Munich Lukon 2010: 70-73
  Google Scholar
• 7 Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril 2012; 98 (3) 511-519
  CrossrefPubMedGoogle Scholar
• 8 Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927; 14: 442-469
  PubMedGoogle Scholar
• 9 Dmowski WP, Ding J, Shen J, Rana N, Fernandez BB, Braun DP. Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis. Hum Reprod 2001; 16 (9) 1802-1808
  CrossrefPubMedGoogle Scholar
• 10 Osteen KG, Bruner-Tran KL, Eisenberg E. Reduced progesterone action during endometrial maturation: a potential risk factor for the development of endometriosis. Fertil Steril 2005; 83 (3) 529-537
  CrossrefPubMedGoogle Scholar
• 11 Asante A, Taylor RN. Endometriosis: the role of neuroangiogenesis. Annu Rev Physiol 2011; 73: 163-182
  CrossrefPubMedGoogle Scholar
• 12 Meyer R. Zur Frage der heterotopen Epithelwucherung, insbesondere des Peritonealepithels und in die Ovarien. Virch Arch Path Anat Phys 1924; 250: 595-610
  PubMedGoogle Scholar
• 13 Batt RE. A History of Endometriosis. London: Springer; 2011: 85
  CrossrefGoogle Scholar
• 14 Taylor RN, Yu J, Torres PB , et al. Mechanistic and therapeutic implications of angiogenesis in endometriosis. Reprod Sci 2009; 16 (2) 140-146
  CrossrefPubMedGoogle Scholar
• 15 Pearce CL, Templeman C, Rossing MA , et al; Ovarian Cancer Association Consortium. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 2012; 13 (4) 385-394
  CrossrefPubMedGoogle Scholar
• 16 Gargett CE, Masuda H. Adult stem cells in the endometrium. Mol Hum Reprod 2010; 16 (11) 818-834
  CrossrefPubMedGoogle Scholar
• 17 Figueira PG, Abrão MS, Krikun G, Taylor HS. Stem cells in endometrium and their role in the pathogenesis of endometriosis. Ann N Y Acad Sci 2011; 1221: 10-17
  CrossrefPubMedGoogle Scholar
• 18 Oberg S, Peters JH, DeMeester TR , et al. Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease. Ann Surg 1997; 226 (4) 522-530 , discussion 530–532
  CrossrefPubMedGoogle Scholar
• 19 Matsumoto M, Yokoyama H, Suzuki H, Shiraishi-Yokoyama H, Hibi T. Retinoic acid formation from retinol in the human gastric mucosa: role of class IV alcohol dehydrogenase and its relevance to morphological changes. Am J Physiol Gastrointest Liver Physiol 2005; 289 (3) G429-G433
  CrossrefPubMedGoogle Scholar
• 20 Fisseler-Eckhoff A, Rothstein D, Müller KM. Neovascularization in hyperplastic, metaplastic and potentially preneoplastic lesions of the bronchial mucosa. Virchows Arch 1996; 429 (2-3) 95-100
  PubMedGoogle Scholar
• 21 Yoon JH, Koo JS, Norford D, Guzman K, Gray T, Nettesheim P. Lysozyme expression during metaplastic squamous differentiation of retinoic acid-deficient human tracheobronchial epithelial cells. Am J Respir Cell Mol Biol 1999; 20 (4) 573-581
  CrossrefPubMedGoogle Scholar
• 22 Jetten AM, Vollberg TM, Nervi C. Hyperplasia and squamous metaplasia in the tracheobronchial epithelium: alterations in the balance of growth and differentiation factors. Adv Exp Med Biol 1992; 320: 89-93
  PubMedGoogle Scholar
• 23 Wu J, Zhang Y, Liu Q, Zhong W, Xia Z. All-trans retinoic acid attenuates airway inflammation by inhibiting Th2 and Th17 response in experimental allergic asthma. BMC Immunol 2013; 14: 28
  CrossrefPubMedGoogle Scholar
• 24 Chen F, Marquez H, Kim YK , et al. Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice. J Clin Invest 2014; 124 (2) 801-811
  CrossrefPubMedGoogle Scholar
• 25 Duits LC, Phoa KN, Curvers WL , et al. Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut 2015; 64 (5) 700-706
  CrossrefPubMedGoogle Scholar
• 26 Herfs M, Hubert P, Poirrier AL , et al. Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy. Am J Respir Cell Mol Biol 2012; 47 (1) 67-79
  CrossrefPubMedGoogle Scholar
• 27 Ehrlich P. [The partial function of cells. (Nobel Prize address given on 11 December 1908 at Stockholm)]. Int Arch Allergy Appl Immunol 1954; 5 (2) 67-86
  CrossrefPubMedGoogle Scholar
• 28 Meigs JV. Endometrial hematomas of the ovary. Boston Med Surg J 1922; 187: 1-13
  CrossrefPubMedGoogle Scholar
• 29 Weed JC, Arquembourg PC. Endometriosis: can it produce an autoimmune response resulting in infertility?. Clin Obstet Gynecol 1980; 23 (3) 885-893
  CrossrefPubMedGoogle Scholar
• 30 Lessey BA, Lebovic DI, Taylor RN. Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects. Semin Reprod Med 2013; 31 (2) 109-124
  Article in Thieme ConnectPubMedGoogle Scholar
• 31 Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 2002; 17 (10) 2715-2724
  CrossrefPubMedGoogle Scholar
• 32 Bungum HF, Vestergaard C, Knudsen UB. Endometriosis and type 1 allergies/immediate type hypersensitivity: a systematic review. Eur J Obstet Gynecol Reprod Biol 2014; 179: 209-215
  CrossrefPubMedGoogle Scholar
• 33 Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update 2013; 19 (4) 406-418
  CrossrefPubMedGoogle Scholar
• 34 Bianco B, André GM, Vilarino FL , et al. The possible role of genetic variants in autoimmune-related genes in the development of endometriosis. Hum Immunol 2012; 73 (3) 306-315
  CrossrefPubMedGoogle Scholar
• 35 Dmowski WP, Gebel HM, Braun DP. The role of cell-mediated immunity in pathogenesis of endometriosis. Acta Obstet Gynecol Scand Suppl 1994; 159: 7-14
  PubMedGoogle Scholar
• 36 Haney AF, Muscato JJ, Weinberg JB. Peritoneal fluid cell populations in infertility patients. Fertil Steril 1981; 35 (6) 696-698
  PubMedGoogle Scholar
• 37 Halme J, Becker S, Hammond MG, Raj MH, Raj S. Increased activation of pelvic macrophages in infertile women with mild endometriosis. Am J Obstet Gynecol 1983; 145 (3) 333-337
  CrossrefPubMedGoogle Scholar
• 38 Wieser F, Wu J, Shen Z, Taylor RN, Sidell N. Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis. Fertil Steril 2012; 97 (6) 1430-1437
  CrossrefPubMedGoogle Scholar
• 39 Leiva MC, Hasty LA, Pfeifer S, Mastroianni Jr L, Lyttle CR. Increased chemotactic activity of peritoneal fluid in patients with endometriosis. Am J Obstet Gynecol 1993; 168 (2) 592-598
  CrossrefPubMedGoogle Scholar
• 40 Khorram O, Taylor RN, Ryan IP, Schall TJ, Landers DV. Peritoneal fluid concentrations of the cytokine RANTES correlate with the severity of endometriosis. Am J Obstet Gynecol 1993; 169 (6) 1545-1549
  CrossrefPubMedGoogle Scholar
• 41 Akoum A, Lemay A, Brunet C, Hébert J. Secretion of monocyte chemotactic protein-1 by cytokine-stimulated endometrial cells of women with endometriosis. Le groupe d'investigation en gynécologie. Fertil Steril 1995; 63 (2) 322-328
  PubMedGoogle Scholar
• 42 Na YJ, Lee DH, Kim SC , et al. Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes. Arch Gynecol Obstet 2011; 283 (6) 1333-1341
  CrossrefPubMedGoogle Scholar
• 43 Hornung D, Dohrn K, Sotlar K , et al. Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis. J Clin Endocrinol Metab 2000; 85 (7) 2604-2608
  CrossrefPubMedGoogle Scholar
• 44 Oral E, Seli E, Bahtiyar MO, Jones EE, Arici A. Growth-regulated alpha expression in human preovulatory follicles and ovarian cells. Am J Reprod Immunol 1997; 38 (1) 19-25
  CrossrefPubMedGoogle Scholar
• 45 Mueller MD, Mazzucchelli L, Buri C, Lebovic DI, Dreher E, Taylor RN. Epithelial neutrophil-activating peptide 78 concentrations are elevated in the peritoneal fluid of women with endometriosis. Fertil Steril 2003; (79) (Suppl. 01) 815-820
  PubMedGoogle Scholar
• 46 Ryan IP, Tseng JF, Schriock ED, Khorram O, Landers DV, Taylor RN. Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril 1995; 63 (4) 929-932
  PubMedGoogle Scholar
• 47 Arici A, Tazuke SI, Attar E, Kliman HJ, Olive DL. Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells. Mol Hum Reprod 1996; 2 (1) 40-45
  CrossrefPubMedGoogle Scholar
• 48 Ruiz A, Salvo VA, Ruiz LA, Báez P, García M, Flores I. Basal and steroid hormone-regulated expression of CXCR4 in human endometrium and endometriosis. Reprod Sci 2010; 17 (10) 894-903
  CrossrefPubMedGoogle Scholar
• 49 Hornung D, Klingel K, Dohrn K, Kandolf R, Wallwiener D, Taylor RN. Regulated on activation, normal T-cell-expressed and -secreted mRNA expression in normal endometrium and endometriotic implants: assessment of autocrine/paracrine regulation by in situ hybridization. Am J Pathol 2001; 158 (6) 1949-1954
  CrossrefPubMedGoogle Scholar
• 50 Furuya M, Suyama T, Usui H , et al. Up-regulation of CXC chemokines and their receptors: implications for proinflammatory microenvironments of ovarian carcinomas and endometriosis. Hum Pathol 2007; 38 (11) 1676-1687
  CrossrefPubMedGoogle Scholar
• 51 Ulukus M, Ulukus EC, Tavmergen Goker EN, Tavmergen E, Zheng W, Arici A. Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis. Fertil Steril 2009; 91 (3) 687-693
  CrossrefPubMedGoogle Scholar
• 52 Kelly MG, Francisco AM, Cimic A , et al. Type 2 endometrial cancer is associated with a high density of tumor-associated macrophages in the stromal compartment. Reprod Sci 2015; (In press)
  PubMedGoogle Scholar
• 53 Hornung D, Ryan IP, Chao VA, Vigne JL, Schriock ED, Taylor RN. Immunolocalization and regulation of the chemokine RANTES in human endometrial and endometriosis tissues and cells. J Clin Endocrinol Metab 1997; 82 (5) 1621-1628
  CrossrefPubMedGoogle Scholar
• 54 Wieser F, Vigne JL, Ryan I, Hornung D, Djalali S, Taylor RN. Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis. J Clin Endocrinol Metab 2005; 90 (12) 6441-6447
  CrossrefPubMedGoogle Scholar
• 55 Wang XQ, Yu J, Luo XZ , et al. The high level of RANTES in the ectopic milieu recruits macrophages and induces their tolerance in progression of endometriosis. J Mol Endocrinol 2010; 45 (5) 291-299
  CrossrefPubMedGoogle Scholar
• 56 Brosens IA, Koninckx PR, Corveleyn PA. A study of plasma progesterone, oestradiol-17beta, prolactin and LH levels, and of the luteal phase appearance of the ovaries in patients with endometriosis and infertility. Br J Obstet Gynaecol 1978; 85 (4) 246-250
  CrossrefPubMedGoogle Scholar
• 57 Barry-Kinsella C, Sharma SC, Cottell E, Harrison RF. Mid to late luteal phase steroids in minimal stage endometriosis and unexplained infertility. Eur J Obstet Gynecol Reprod Biol 1994; 54 (2) 113-118
  CrossrefPubMedGoogle Scholar
• 58 Cheesman KL, Ben-Nun Chatterton Jr RT, Cohen MR. Relationship of luteinizing hormone, pregnanediol-3-glucuronide, and estriol-16-glucuronide in urine of infertile women with endometriosis. Fertil Steril 1982; 38 (5) 542-548
  PubMedGoogle Scholar
• 59 Pittaway DE, Maxson W, Daniell J, Herbert C, Wentz AC. Luteal phase defects in infertility patients with endometriosis. Fertil Steril 1983; 39 (5) 712-713
  PubMedGoogle Scholar
• 60 Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S. Role of nuclear progesterone receptor isoforms in uterine pathophysiology. Hum Reprod Update 2015; 21 (2) 155-173
  CrossrefPubMedGoogle Scholar
• 61 Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab 2000; 85 (8) 2897-2902
  CrossrefPubMedGoogle Scholar
• 62 Taylor RN, Lundeen SG, Giudice LC. Emerging role of genomics in endometriosis research. Fertil Steril 2002; 78 (4) 694-698
  CrossrefPubMedGoogle Scholar
• 63 Kao LC, Germeyer A, Tulac S , et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology 2003; 144 (7) 2870-2881
  CrossrefPubMedGoogle Scholar
• 64 Burney RO, Talbi S, Hamilton AE , et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology 2007; 148 (8) 3814-3826
  CrossrefPubMedGoogle Scholar
• 65 Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis. Epigenetics 2006; 1 (2) 106-111
  CrossrefPubMedGoogle Scholar
• 66 Al-Sabbagh M, Lam EW, Brosens JJ. Mechanisms of endometrial progesterone resistance. Mol Cell Endocrinol 2012; 358 (2) 208-215
  Google Scholar
• 67 Aghajanova L, Hamilton A, Kwintkiewicz J, Vo KC, Giudice LC. Steroidogenic enzyme and key decidualization marker dysregulation in endometrial stromal cells from women with versus without endometriosis. Biol Reprod 2009; 80 (1) 105-114
  CrossrefPubMedGoogle Scholar
• 68 Fazleabas AT. Progesterone resistance in a baboon model of endometriosis. Semin Reprod Med 2010; 28 (1) 75-80
  Article in Thieme ConnectPubMedGoogle Scholar
• 69 Missmer SA, Cramer DW. The epidemiology of endometriosis. Obstet Gynecol Clin North Am 2003; 30 (1) 1-19 , vii
  CrossrefPubMedGoogle Scholar
• 70 Brandenberger AW, Lebovic DI, Tee MK , et al. Oestrogen receptor (ER)-alpha and ER-beta isoforms in normal endometrial and endometriosis-derived stromal cells. Mol Hum Reprod 1999; 5 (7) 651-655
  CrossrefPubMedGoogle Scholar
• 71 Bulun SE, Cheng YH, Pavone ME , et al. Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis. Semin Reprod Med 2010; 28 (1) 36-43
  Article in Thieme ConnectPubMedGoogle Scholar
• 72 Noble LS, Takayama K, Zeitoun KM , et al. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab 1997; 82 (2) 600-606
  CrossrefPubMedGoogle Scholar
• 73 Zhao Y, Gong P, Chen Y , et al. Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis. Sci Transl Med 2015; 7 :271ra9
  PubMedGoogle Scholar
• 74 Kulak Jr J, Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology 2011; 152 (8) 3226-3232
  CrossrefPubMedGoogle Scholar
• 75 Harris HA, Bruner-Tran KL, Zhang X, Osteen KG, Lyttle CR. A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis. Hum Reprod 2005; 20 (4) 936-941
  PubMedGoogle Scholar
• 76 Hornung D, Waite LL, Ricke EA, Bentzien F, Wallwiener D, Taylor RN. Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing effects on monocyte chemotaxis in endometriosis. J Clin Endocrinol Metab 2001; 86 (7) 3108-3114
  CrossrefPubMedGoogle Scholar
• 77 Pritts EA, Zhao D, Ricke E, Waite L, Taylor RN. PPAR-gamma decreases endometrial stromal cell transcription and translation of RANTES in vitro. J Clin Endocrinol Metab 2002; 87 (4) 1841-1844
  PubMedGoogle Scholar
• 78 Ohama Y, Harada T, Iwabe T, Taniguchi F, Takenaka Y, Terakawa N. Peroxisome proliferator-activated receptor-gamma ligand reduced tumor necrosis factor-alpha-induced interleukin-8 production and growth in endometriotic stromal cells. Fertil Steril 2008; 89 (2) 311-317
  CrossrefPubMedGoogle Scholar
• 79 McKinnon B, Bersinger NA, Mueller MD. Peroxisome proliferating activating receptor gamma-independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones. Fertil Steril 2012; 97 (3) 657-664
  CrossrefPubMedGoogle Scholar
• 80 Peeters LL, Vigne JL, Tee MK, Zhao D, Waite LL, Taylor RN. PPAR gamma represses VEGF expression in human endometrial cells: implications for uterine angiogenesis. Angiogenesis 2005; 8 (4) 373-379
  PubMedGoogle Scholar
• 81 Laschke MW, Menger MD. Anti-angiogenic treatment strategies for the therapy of endometriosis. Hum Reprod Update 2012; 18 (6) 682-702
  CrossrefPubMedGoogle Scholar
• 82 Wang L, Waltenberger B, Pferschy-Wenzig EM , et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochem Pharmacol 2014; 92 (1) 73-89
  CrossrefPubMedGoogle Scholar
• 83 Waite LL, Louie RE, Taylor RN. Circulating activators of peroxisome proliferator-activated receptors are reduced in preeclamptic pregnancy. J Clin Endocrinol Metab 2005; 90 (2) 620-626
  CrossrefPubMedGoogle Scholar
• 84 Lebovic DI, Kir M, Casey CL. Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril 2004; 82 (Suppl. 03) 1008-1013
  CrossrefPubMedGoogle Scholar
• 85 Nenicu A, Körbel C, Gu Y, Menger MD, Laschke MW. Combined blockade of angiotensin II type 1 receptor and activation of peroxisome proliferator-activated receptor-γ by telmisartan effectively inhibits vascularization and growth of murine endometriosis-like lesions. Hum Reprod 2014; 29 (5) 1011-1024
  CrossrefPubMedGoogle Scholar
• 86 Lebovic DI, Mwenda JM, Chai DC , et al. PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controlled study. Fertil Steril 2007; 88 (4, Suppl): 1108-1119
  CrossrefPubMedGoogle Scholar
• 87 Loughney AD, Kumarendran MK, Thomas EJ, Redfern CP. Variation in the expression of cellular retinoid binding proteins in human endometrium throughout the menstrual cycle. Hum Reprod 1995; 10 (5) 1297-1304
  PubMedGoogle Scholar
• 88 Kumarendran MK, Loughney AD, Prentice A, Thomas EJ, Redfern CP. Nuclear retinoid receptor expression in normal human endometrium throughout the menstrual cycle. Mol Hum Reprod 1996; 2 (2) 123-129
  CrossrefPubMedGoogle Scholar
• 89 Osteen KG, Keller NR, Feltus FA, Melner MH. Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium. Gynecol Obstet Invest 1999; 48 (Suppl. 01) 2-13
  CrossrefPubMedGoogle Scholar
• 90 Bo WJ, Smith MS. The effect of retinol and retinoic acid on the morphology of the rat uterus. Anat Rec 1966; 156 (1) 5-9
  CrossrefPubMedGoogle Scholar
• 91 Thompson JN, Howell JM, Pitt GA. Vitamin A and reproduction in rats. Proc R Soc Lond B Biol Sci 1964; 159: 510-535
  CrossrefPubMedGoogle Scholar
• 92 Li XH, Kakkad B, Ong DE. Estrogen directly induces expression of retinoic acid biosynthetic enzymes, compartmentalized between the epithelium and underlying stromal cells in rat uterus. Endocrinology 2004; 145 (10) 4756-4762
  CrossrefPubMedGoogle Scholar
• 93 Zheng WL, Sierra-Rivera E, Luan J, Osteen KG, Ong DE. Retinoic acid synthesis and expression of cellular retinol-binding protein and cellular retinoic acid-binding protein type II are concurrent with decidualization of rat uterine stromal cells. Endocrinology 2000; 141 (2) 802-808
  PubMedGoogle Scholar
• 94 Bruner-Tran KL, Eisenberg E, Yeaman GR, Anderson TA, McBean J, Osteen KG. Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice. J Clin Endocrinol Metab 2002; 87 (10) 4782-4791
  CrossrefPubMedGoogle Scholar
• 95 Wu J, Taylor RN, Sidell N. Retinoic acid regulates gap junction intercellular communication in human endometrial stromal cells through modulation of the phosphorylation status of connexin 43. J Cell Physiol 2013; 228 (4) 903-910
  Google Scholar
• 96 Nozaki Y, Yamagata T, Sugiyama M, Ikoma S, Kinoshita K, Funauchi M. Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis. Clin Immunol 2006; 119 (3) 272-279
  CrossrefPubMedGoogle Scholar
• 97 Sago K, Teitelbaum SL, Venstrom K, Reichardt LF, Ross FP. The integrin alphavbeta5 is expressed on avian osteoclast precursors and regulated by retinoic acid. J Bone Miner Res 1999; 14 (1) 32-38
  CrossrefPubMedGoogle Scholar
• 98 Sidell N, Feng Y, Hao L , et al. Retinoic acid is a cofactor for translational regulation of vascular endothelial growth factor in human endometrial stromal cells. Mol Endocrinol 2010; 24 (1) 148-160
  CrossrefPubMedGoogle Scholar
• 99 Sawatsri S, Desai N, Rock JA, Sidell N. Retinoic acid suppresses interleukin-6 production in human endometrial cells. Fertil Steril 2000; 73 (5) 1012-1019
  CrossrefPubMedGoogle Scholar
• 100 Sharpe-Timms KL. Endometrial anomalies in women with endometriosis. Ann N Y Acad Sci 2001; 943: 131-147
  CrossrefPubMedGoogle Scholar
• 101 Pavone ME, Reierstad S, Sun H, Milad M, Bulun SE, Cheng YH. Altered retinoid uptake and action contributes to cell survival in endometriosis. J Clin Endocrinol Metab 2010; 95 (11) E300-E309
  CrossrefPubMedGoogle Scholar
• 102 Pierzchalski K, Taylor RN, Nezhat C , et al. Retinoic acid biosynthesis is impaired in human and murine endometriosis. Biol Reprod 2014; 91 (4) 84
  CrossrefPubMedGoogle Scholar
• 103 Pavone ME, Dyson M, Reirstad S , et al. Endometriosis expresses a molecular pattern consistent with decreased retinoid uptake, metabolism and action. Hum Reprod 2011; 26 (8) 2157-2164
  CrossrefPubMedGoogle Scholar
• 104 Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochim Biophys Acta 2012; 1821 (1) 152-167
  CrossrefPubMedGoogle Scholar
• 105 Cvetković D, Williams SJ, Hamilton TC. Loss of cellular retinol-binding protein 1 gene expression in microdissected human ovarian cancer. Clin Cancer Res 2003; 9 (3) 1013-1020
  PubMedGoogle Scholar
• 106 Kuppumbatti YS, Bleiweiss IJ, Mandeli JP, Waxman S, Mira-Y-Lopez R. Cellular retinol-binding protein expression and breast cancer. J Natl Cancer Inst 2000; 92 (6) 475-480
  CrossrefPubMedGoogle Scholar
• 107 Esteller M, Guo M, Moreno V , et al. Hypermethylation-associated Inactivation of the Cellular Retinol-Binding-Protein 1 Gene in Human Cancer. Cancer Res 2002; 62 (20) 5902-5905
  PubMedGoogle Scholar
• 108 Mendoza-Rodriguez M, Arreola H, Valdivia A , et al. Cellular retinol binding protein 1 could be a tumor suppressor gene in cervical cancer. Int J Clin Exp Pathol 2013; 6 (9) 1817-1825
  PubMedGoogle Scholar
• 109 Pierzchalski K, Yu J, Norman V, Kane MA. CrbpI regulates mammary retinoic acid homeostasis and the mammary microenvironment. FASEB J 2013; 27 (5) 1904-1916
  CrossrefPubMedGoogle Scholar
• 110 Xu L, Song C, Ni M, Meng F, Xie H, Li G. Cellular retinol-binding protein 1 (CRBP-1) regulates osteogenenesis and adipogenesis of mesenchymal stem cells through inhibiting RXRα-induced β-catenin degradation. Int J Biochem Cell Biol 2012; 44 (4) 612-619
  CrossrefPubMedGoogle Scholar
• 111 Yu J, Boicea A, Barrett KL , et al. Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis. Mol Hum Reprod 2014; 20 (3) 260-270
  CrossrefPubMedGoogle Scholar
• 112 Augoulea A, Mastorakos G, Lambrinoudaki I, Christodoulakos G, Creatsas G. The role of the oxidative-stress in the endometriosis-related infertility. Gynecol Endocrinol 2009; 25 (2) 75-81
  CrossrefPubMedGoogle Scholar
• 113 Stock A, Booth S, Cerundolo V. Prostaglandin E2 suppresses the differentiation of retinoic acid-producing dendritic cells in mice and humans. J Exp Med 2011; 208 (4) 761-773
  CrossrefPubMedGoogle Scholar
• 114 Corlazzoli F, Rossetti S, Bistulfi G, Ren M, Sacchi N. Derangement of a factor upstream of RARalpha triggers the repression of a pleiotropic epigenetic network. PLoS ONE 2009; 4 (1) e4305
  CrossrefPubMedGoogle Scholar
• 115 Tannous-Khuri L, Talmage DA. Decreased cellular retinol-binding protein expression coincides with the loss of retinol responsiveness in rat cervical epithelial cells. Exp Cell Res 1997; 230 (1) 38-44
  CrossrefPubMedGoogle Scholar
• 116 Wu MH, Lu CW, Chuang PC, Tsai SJ. Prostaglandin E2: the master of endometriosis?. Exp Biol Med (Maywood) 2010; 235 (6) 668-677
  CrossrefPubMedGoogle Scholar
• 117 Budhu A, Gillilan R, Noy N. Localization of the RAR interaction domain of cellular retinoic acid binding protein-II. J Mol Biol 2001; 305 (4) 939-949
  CrossrefPubMedGoogle Scholar
• 118 Wang X, Allen C, Ballow M. Retinoic acid enhances the production of IL-10 while reducing the synthesis of IL-12 and TNF-alpha from LPS-stimulated monocytes/macrophages. J Clin Immunol 2007; 27 (2) 193-200
  CrossrefPubMedGoogle Scholar
• 119 Saxon A, Keld B, Braun J, Dotson A, Sidell N. Long-term administration of 13-cis retinoic acid in common variable immunodeficiency: circulating interleukin-6 levels, B-cell surface molecule display, and in vitro and in vivo B-cell antibody production. Immunology 1993; 80 (3) 477-487
  PubMedGoogle Scholar
• 120 Sidell N, Taga T, Hirano T, Kishimoto T, Saxon A. Retinoic acid-induced growth inhibition of a human myeloma cell line via down-regulation of IL-6 receptors. J Immunol 1991; 146 (11) 3809-3814
  PubMedGoogle Scholar
• 121 Adelman DC, Matsuda TF, Hirano TF, Kishimoto TF, Saxon A. Elevated serum interleukin-6 associated with a failure in B cell differentiation in common variable immunodeficiency. J Allergy Clin Immunol 1990; 86 (4) 512-521
  CrossrefPubMedGoogle Scholar
• 122 Tseng JF, Ryan IP, Milam TD , et al. Interleukin-6 secretion in vitro is up-regulated in ectopic and eutopic endometrial stromal cells from women with endometriosis. J Clin Endocrinol Metab 1996; 81 (3) 1118-1122
  CrossrefPubMedGoogle Scholar
• 123 Han S, Sidell N. Peroxisome-proliferator-activated-receptor gamma (PPARgamma) independent induction of CD36 in THP-1 monocytes by retinoic acid. Immunology 2002; 106 (1) 53-59
  CrossrefPubMedGoogle Scholar
• 124 Wuttge DM, Romert A, Eriksson U, Törmä H, Hansson GK, Sirsjö A. Induction of CD36 by all-trans retinoic acid: retinoic acid receptor signaling in the pathogenesis of atherosclerosis. FASEB J 2001; 15 (7) 1221-1223
  PubMedGoogle Scholar
• 125 Fadok VA, Warner ML, Bratton DL, Henson PM. CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (alpha v beta 3). J Immunol 1998; 161 (11) 6250-6257
  PubMedGoogle Scholar
• 126 Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 1993; 268 (16) 11811-11816
  PubMedGoogle Scholar
• 127 Nicholson AC, Frieda S, Pearce A, Silverstein RL. Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines. Evidence implicating the lipid moiety of the lipoprotein as the binding site. Arterioscler Thromb Vasc Biol 1995; 15 (2) 269-275
  CrossrefPubMedGoogle Scholar
• 128 Santanam N, Murphy AA, Parthasarathy S. Macrophages, oxidation, and endometriosis. Ann N Y Acad Sci 2002; 955: 183-198 , discussion 19–200, 396–406
  CrossrefPubMedGoogle Scholar
• 129 van Neerven S, Regen T, Wolf D , et al. Inflammatory chemokine release of astrocytes in vitro is reduced by all-trans retinoic acid. J Neurochem 2010; 114 (5) 1511-1526
  PubMedGoogle Scholar
• 130 Bruner-Tran KL, Osteen KG, Duleba AJ. Simvastatin protects against the development of endometriosis in a nude mouse model. J Clin Endocrinol Metab 2009; 94 (7) 2489-2494
  CrossrefPubMedGoogle Scholar
• 131 Oktem M, Esinler I, Eroglu D, Haberal N, Bayraktar N, Zeyneloglu HB. High-dose atorvastatin causes regression of endometriotic implants: a rat model. Hum Reprod 2007; 22 (5) 1474-1480
  CrossrefPubMedGoogle Scholar
• 132 Yilmaz B, Ozat M, Kilic S , et al. Atorvastatin causes regression of endometriotic implants in a rat model. Reprod Biomed Online 2010; 20 (2) 291-299
  CrossrefPubMedGoogle Scholar
• 133 Sokalska A, Anderson M, Villanueva J , et al. Effects of simvastatin on retinoic acid system in primary human endometrial stromal cells and in a chimeric model of human endometriosis. J Clin Endocrinol Metab 2013; 98 (3) E463-E471
  CrossrefPubMedGoogle Scholar
• 134 Cui J, Zhu N, Wang Q , et al. p38 MAPK contributes to CD54 expression and the enhancement of phagocytic activity during macrophage development. Cell Immunol 2009; 256 (1-2) 6-11
  CrossrefPubMedGoogle Scholar
• 135 Ghosn EE, Cassado AA, Govoni GR , et al. Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc Natl Acad Sci U S A 2010; 107 (6) 2568-2573
  CrossrefPubMedGoogle Scholar
• 136 Hoffman SM, Fleming SD. Natural Helicobacter infection modulates mouse intestinal muscularis macrophage responses. Cell Biochem Funct 2010; 28 (8) 686-694
  CrossrefPubMedGoogle Scholar
• 137 Rosas M, Thomas B, Stacey M, Gordon S, Taylor PR. The myeloid 7/4-antigen defines recently generated inflammatory macrophages and is synonymous with Ly-6B. J Leukoc Biol 2010; 88 (1) 169-180
  CrossrefPubMedGoogle Scholar
• 138 Prus E, Fibach E. Retinoic acid induction of CD38 antigen expression on normal and leukemic human myeloid cells: relationship with cell differentiation. Leuk Lymphoma 2003; 44 (4) 691-698
  CrossrefPubMedGoogle Scholar
• 139 Kishimoto H, Hoshino S, Ohori M , et al. Molecular mechanism of human CD38 gene expression by retinoic acid. Identification of retinoic acid response element in the first intron. J Biol Chem 1998; 273 (25) 15429-15434
  CrossrefPubMedGoogle Scholar
• 140 Musso T, Deaglio S, Franco L , et al. CD38 expression and functional activities are up-regulated by IFN-gamma on human monocytes and monocytic cell lines. J Leukoc Biol 2001; 69 (4) 605-612
  PubMedGoogle Scholar
• 141 Ozer H, Boztosun A, Açmaz G, Atilgan R, Akkar OB, Kosar MI. The efficacy of bevacizumab, sorafenib, and retinoic acid on rat endometriosis model. Reprod Sci 2013; 20 (1) 26-32
  CrossrefPubMedGoogle Scholar
• 142 Pelch KE, Schroder AL, Kimball PA, Sharpe-Timms KL, Davis JW, Nagel SC. Aberrant gene expression profile in a mouse model of endometriosis mirrors that observed in women. Fertil Steril 2010; 93 (5) 1615-1627 , e18
  CrossrefPubMedGoogle Scholar
• 143 Shah DK. Diminished ovarian reserve and endometriosis: insult upon injury. Semin Reprod Med 2013; 31 (2) 144-149
  Article in Thieme ConnectPubMedGoogle Scholar
• 144 Pauli SA, Session DR, Shang W , et al. Analysis of follicular fluid retinoids in women undergoing in vitro fertilization: retinoic acid influences embryo quality and is reduced in women with endometriosis. Reprod Sci 2013; 20 (9) 1116-1124
  CrossrefPubMedGoogle Scholar
• 145 Moulas AN, Gerogianni IC, Papadopoulos D, Gourgoulianis KI. Serum retinoic acid, retinol and retinyl palmitate levels in patients with lung cancer. Respirology 2006; 11 (2) 169-174
  CrossrefPubMedGoogle Scholar
• 146 Sedjo RL, Ranger-Moore J, Foote J , et al. Circulating endogenous retinoic acid concentrations among participants enrolled in a randomized placebo-controlled clinical trial of retinyl palmitate. Cancer Epidemiol Biomarkers Prev 2004; 13 (11, Pt 1) 1687-1692
  PubMedGoogle Scholar
• 147 Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 1984; 64 (2) 151-154
  PubMedGoogle Scholar
• 148 Dunselman GA, Vermeulen N, Becker C , et al; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014; 29 (3) 400-412
  CrossrefPubMedGoogle Scholar
• 149 Rogers PA, D'Hooghe TM, Fazleabas A , et al. Defining future directions for endometriosis research: workshop report from the 2011 World Congress of Endometriosis In Montpellier, France. Reprod Sci 2013; 20 (5) 483-499
  CrossrefPubMedGoogle Scholar
• 150 de Groot CJ, Murai JT, Vigne JL, Taylor RN. Eicosanoid secretion by human endothelial cells exposed to normal pregnancy and preeclampsia plasma in vitro. Prostaglandins Leukot Essent Fatty Acids 1998; 58 (2) 91-97
  CrossrefPubMedGoogle Scholar