İmplantasyon ve desidualizasyon esnasında fare uterus dokusunda PROK1 ve PROKR1’in ekspresyonu

Year 2021, Volume: 92 Issue: 1, 49 - 59, 15.01.2021

Duygu Mutluay Özlem Özbey Leyla Kılınç Jale Öner Hakan Öner İsmail Üstünel

https://doi.org/10.33188/vetheder.774408

Abstract

İmplantasyon, embriyonun özel hücreleri olan trofoektoderm ve trophoblast vasıtasıyla uterus dokusuyla bağlantı kurulması ile son bulan bir süreçtir. Başarılı bir implantasyon, plasentasyon ve sonrasında gebeliğin gerçekleşebişmesi için damardan zengin bir endometriyum, koordine olmuş bir damar gelişimi ve plasental villöz damarların genişlemesine gereksinim vardır. Bu bilgiler anjiyogenezin gebeliğin erken dönemleri için önemli fizyolojik bir süreç olduğunu göstermiştir. Prokinetisin ailesinin bir üyesi olan vasküler endoteliyal büyüme faktörü (EG-VEGF) diğer bir adıyla prokinetisin 1 (PROK1) plasentayı da içine alan spesifik endokrin dokular için anjiyogenik bir faktör olarak rapor edilmiştir. Biyolojik aktivitesini iki G protein bağlı reseptör, prokinetisin reseptör 1 (PROKR1) ve prokinetisin reseptör 2 (PROKR2) aracılığı ile gerçekleştirir. Trofoblast invazyonunu kontrol eden PROK1ve PROKR1 plasentada eksprese edilmektedir. Ayrıca, PROK1 plasental anjiyogenezi kontrol eder ve yüksek oranda birinci trimester boyunca eksprese edilmektedir. Çalışmamızda kullanılan dişi fareler, östrus siklusu tayini yapıldıktan sonra, 1 gece erkek fareler ile birlikte bırakılarak gebe kalmaları sağlandı. Vaginal plak (tıkaç) görülen dişiler gebe olarak değerlendirildi. Gebeliğin 1, 2, 3, 4, 5, 6, 7 ve 8. günlerinde alınan uterus doku örneklerinde Western Blot yöntemi kullanılarak PROK1, PROKR1 proteinlerinin ekspresyon analizi yapıldı ve günler arasında bir farklılığın olup olmadığını belirlemek için varyans analizi yöntemi kullanıldı. Çalışmamızda PROK1 ve PROKR1 proteinlerinin gebeliğin ilk 8 günü boyunca eksprese edildiği görüldü. Bu bulgular bize PROK1 ve PROKR1 proteinlerinin erken embriyo gelişimi ve implantasyon sırasında eksprese edildiğini ve bu proteinlerin embriyo gelişiminde önemli roller oynuyor olabileceğini önermiştir.

Keywords

Desidualizasyon, İmplantasyon, Preimplantasyon, Prokinetisin 1, Prokinetisin reseptör 1

Supporting Institution

Mehmet Akif Ersoy Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü

Project Number

0316-NAP-16

Thanks

MAKÜ-BAP projesi kapsamındaki çalışmamıza verdiği maddi destek için MAKÜ-BAP Koordinatörlüğüne teşekkürlerimizi sunarız.

Expression of PROK-1 and PROKR-1 in mouse uterine tissue during implantation and decidualization

Abstract

Implantation is a process culminating whereby specialized cells of the embryo, the trophectoderm and trophoblast, establish contact with a specialized tissue of the mother, the uterus. During this process trophoblast invades the maternal endometrium and makes contact with the maternal blood supply, which is critical for establishment of pregnancy. Successful implantation, placentation and subsequent gestation require coordinated vascular development to provide a richly vascularized endometrium for implantation and the development and expansion of the placental villous vasculature to facilitate transport of nutrients and oxygen to the embryo. This knowledge supports that angiogenesis is an essential physiological component of implantation, and placental and embryonic development in early stages of pregnancy. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1(PROK1), is the member of the prokineticin family which is an angiogenic factor reported to be specific for endocrine tissues, including the placenta. Its biological activity is mediated via two G protein coupled receptors, prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). PROK1 and PROKR1 are expressed in placenta and control trophoblast invasion. Additionally, PROKR1 controls placental angiogenesis and is highly expressed throughout the first trimester. Mice were mated overnight after determining of estrus. Pregnant mice were determined by vaginal plug control. Expressions of PROK-1 and PROKR1 proteins were determined by Western Blot analysis in uterine tissue samples taken at 1, 2, 3, 4, 5, 6, 7, and 8 days of gestation and the results were compared statistically by using the variance analysis to determine whether there was a significant difference between days. In our study, we showed that PROK1 and PROKR1 proteins were expressed during the first 8 days of gestation. These findings suggested that PROK1 and PROKR1 proteins were expressed during early embryo development and implantation and these proteins may play important roles in embryo development.

Keywords

Desidualization, Implantation, Preimplantation, Prokineticin, Prokineticin receptor 1

Project Number

0316-NAP-16

References

• Afonso S, Romagnano L, Babiarz B (1997): The expression and function of cystatin C and cathepsin B and cathepsin L during mouse embryo implantation and placentation. Development, 124, 3415-3425.
• Alfaidy N, Hoffmann P, Gillois P, Gueniffey A, Lebayle C, Garçin H, Thomas-Cadi C, Bessonnat J, Coutton C, Villaret L, Quenard N, Bergues U, Feige JJ, Hennebicq S, Brouillet S (2015): PROK1 Level in the Follicular Microenvironment: A New Noninvasive Predictive Biomarker of Embryo Implantation. J Clin Endocrinol Metab, 101(2), 435-444.
• Aplin JD (1988): Cellular biology of the endometrium. 187-202. In: Wynn RM, Jolie WP, (Ed), Biology of the Uterus. Ed.3 Plenum Press, New York.
• Baschat AA (2004): Fetal responses to placental insufficiency: an update. BJOG, 111(10), 1031–1041.
• Battersby S, Critchley HO, Morgan K, Millar RP, Jabbour HN (2004): Expression and regulation of the prokineticins (endocrine gland-derived vascular endothelial growth factor and Bv8) and their receptors in the human endometrium across the menstrual cycle. J Clin Endocrinol Metab, 89, 2463–2469.
• Brouillet S, Hoffmann P, Benharouga M, Salomon A, Schaal JP, Feige JJ, Alfaidy N (2010): Molecular characterization of EG-VEGFmediated angiogenesis: differential effects on microvascular and macrovascular endothelial cells. Mol Biol Cell, 21, 2832–2843.
• Brouillet S, Hoffmann P, Chauvet S, Salomon A, Chamboredon S, Sergent F, Benharouga M, Feige JJ, Alfaidy N (2012): Revisiting the role of hCG: new regulation of the angiogenic factor EG-VEGF and its receptors. Cell Mol Life Sci, 69(9), 1537–1550.
• Brouillet S, Hoffmann P, Feige J.J, Alfaidy N (2012): EG-VEGF: a key endocrine factor in placental development. Trends Endocrinol Metab, 23(10), 501-508.
• Brouillet S, Murthi P, Hoffmann P, Salomon A, Sergent f, De Mazancourt P, Dakouane-Giudicelli M, Dieudonne´ M. N, Rozenberg P, Vaiman D, Barbaux S, Benharouga M, Feige J, Alfaidy N (2013): EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR). Cell Mol Life Sci, 70, 511–525.
• Brouillet S, Hoffmann P, Alfaidy N, Feige JJ (2014): Prokineticins: new regulatory peptides in human reproduction. Med Sci (Paris), 30, 274–279.
• Catalano RD, Lannagan TR, Gorowiec M, Denison FC, Norman JE, Jabbour HN (2010): Prokineticins: novel mediators of inflammatory and contractile pathways at parturition? Mol Hum Reprod, 16, 311–319.
• Church HJ, Vicovac LM, Williams JDL, Hey NA, Aplin JD (1996): Laminins 2 and 4 are expressed by human decidual cells. Lab Invest, 74, 21-32.
• Cook IH, Evans J, Maldonado-Perez D, Critchley HO, Sales KJ, Jabbour HN (2010): Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/ NFAT signalling pathway. Mol Hum Reprod, 16, 158–169.
• Denison FC, Battersby S, King AE, Szuber M, Jabbour HN (2008): Prokineticin-1: a novel mediator of the inflammatory response in third-trimester human placenta. Endocrinology, 149, 3470–3477.
• Dorsch M, Qiu Y, Soler D, Frank N, Duong T, Goodearl A, O’Neil S, Lora J, Fraser CC (2005): PK1/EG-VEGF induces monocyte differentiation and activation. J Leukoc Biol, 78, 426–434.
• Evans J, Catalano RD, Morgan K, Critchley HO, Millar RP, Jabbour HN (2008): Prokineticin 1 signaling and gene regulation in early human pregnancy. Endocrinology, 149, 2877–2887.
• Evans J, Catalano RD, Brown P, Sherwin R, Critchley HO, Fazleabas AT, Jabbour HN (2009): Prokineticin 1 mediates fetal-maternal dialogue regulating endometrial leukemia inhibitory factor. FASEBJ, 23, 2165–2175.
• Ferrara N, Frantz G, LeCouter J, Dillard-Telm L, Pham T, Draksharapu A, Giordano T, Peale F (2003): Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am J Pathol, 162, 1881–1893.
• Fraser HM, Bell J, Wilson H, Taylor PD, Morgan K, Anderson RA, Duncan WC (2005): Localization and quantification of cyclic changes in the expression of endocrine gland vascular endothelial growth factor in the human corpus luteum. J Clin Endocrinol Metab, 90, 427–434.
• Graham CH, Lala PK (1992): Mechanisms of placental invasion of the uterus and their control. Biochem Cell Biol, 70, 867-74.
• Haouzi D, Mahmoud K, Fourar M, Bendhaou K, Dechaud H, De Vos J, Rème T, Dewailly D, Hamamah S (2009): Identification of new biomarkers of human endometrial receptivity in the natural cycle. Hum Reprod, 24, 198–205.
• Hoffmann P, Feige JJ, Alfaidy N (2006): Expression and oxygen regulation of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy. Endocrinology, 147(4), 1675–1684.
• Hoffmann P, Feige JJ, Alfaidy N (2007): Placental expression of EG-VEGF and its receptors PKR1 (prokineticin receptor-1) and PKR2 throughout mouse gestation. Placenta, 28(10), 1049–1058.
• Hoffmann P, Saoudi Y, Benharouga M, Graham CH, Schaal JP, Mazouni C, Feige JJ, Alfaidy N (2009): Role of EG-VEGF in human placentation: physiological and pathological implications. J Cell Mol Med, 13(8B), 2224–2235.
• Izgut-Uysal VN, Acar N, Birsen I, Ozcan F, Ozbey O, Soylu H, Avci S, Tepekoy F, Akkoyunlu G, Yucel G, Ustunel I (2018): Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart. Tissue Cell. 51, 91-96.
• Kaser A, Winklmayr M, Lepperdinger G, Kreil G (2003): The AVIT protein family. Secreted cysteine-rich vertebrate proteins with diverse functions. EMBO Reports, 4, 469–73.
• Kelly BA, Bond BC, Poston L (2003): Gestational profile of matrix metalloproteinases in rat uterine artery. Mol Hum Reprod, 9, 351-358.
• Kisliouk T, Levy N, Hurwitz A, Meidan R (2003): Presence and regulation of endocrine gland vascular endothelial growth factor/prokineticin-1 and its receptors in ovarian cells. J Clin. Endocrinol Metab, 88, 3700–3707.
• Kisliouk T, Podlovni H, Meidan R (2005): Unique expression and regulatory mechanisms of EG-VEGF/prokineticin-1 and its receptors in the corpus luteum. Ann Anat, 187, 529–537.
• Kisliouk T, Podlovni H, Spanel-Borowski K, Ovadia O, Zhou QY, Meidan R (2005): Prokineticins (endocrine gland-derived vascular endothelial growth factor and BV8) in the bovine ovary: expression and role as mitogens and survival factors for corpus luteum-derived endothelial cells. Endocrinology, 146, 3950–3958.
• LeCouter J, Kowalski J, Foster J, Hass P, Zhang ZM, Dillard-Telm L, Frantz G, Rangell L, DeGuzman L, Keller GA, Peale F, Gurney A, Hillan KJ, Ferrara N (2001): Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature, 412, 877–84.
• LeCouter J, Lin R, Tejada M, Frantz G, Peale F, Hillan KJ, Ferrara N (2003): The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: localization of Bv8 receptors to endothelial cells. PNAS, 100, 2685–90.
• LeCouter J, Zlot C, Tejada M, Peale F, Ferrara N (2004): Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization. PNAS, 101, 16813–16818.
• Li M, Bullock CM, Knauer DJ, Ehlert FJ, Zhou QY (2001): Identification of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle. Mol Pharmacol, 59, 692–698.
• Lockwood CJ, Krıkun G, Hausknecht VA, Papp C. and Schatz F (1998): Matrix Metalloproteinase and Matrix Metalloproteinase Inhıbıtor Expression in Endometrial Stromal Cells during Progestin-Inıtiated Decidualization and Menstruation-Related Progestin Withdrawal. Endocrinology, 139(11), 4607-4613.
• Macdonald LJ, Sales KJ, Grant V, Brown P, Jabbour HN, Catalano RD (2011): Prokineticin 1 induces Dickkopf 1 expression and regulates cell proliferation and decidualization in the human endometrium. Mol Hum Reprod, 17, 626–636.
• Maldonado-Perez D, Evans J, Denison F, Millar RP, Jabbour HN (2007): Potential roles of the prokineticins in reproduction. Trends Endocrin Met, 18, 66–72.
• Maldonado-Perez D, Brown P, Morgan K, Millar RP, Thompson EA, Jabbour HN (2009): Prokineticin 1 modulates IL-8 expression via the calcineurin/NFAT signaling pathway. Biochim Biophys Acta, 1793, 1315–1324. Monnier J, Samson M (2008): Cytokine properties of prokineticins. FEBSJ, 275, 4014–4021.
• Mutluay D, Oner H (2015): Farelerde Preimplantasyon Döneminde Trofoektoderm ve İç Hücre Kütlesinin Oluşumu. MAKU J Health Sci Inst, 3, 1-9.
• Mutluay D, Oner H (2017): The Abelson tyrosine kinase (c-Abl) localization in preimplantation mouse development. Rom J Morphol Embryol, 58(4), 1385-1391.
• Ngan ESW, Lee KY, Yeung WSB, Ngan HYS, Ng EHY, Ho PC (2006): Endocrine gland-derived vascular endothelial growth factor is expressed in human peri-implantation endometrium, but not in endometrial carcinoma. Endocrinology, 147, 88–95.
• Ngan ESW, Tam PKH (2008): Prokineticin-signaling pathway. Int J Biochem Cell B, 40, 1679–1684.
• Piliszek A, Grabarek JB, Frankenberg SR, Plusa B (2016): Cell fate in animal and human blastocysts and the determination of viability. Mol Hum Reprod, 22(10), 681-690.
• Roberts WG, Delaat J, Nagane M, Huang S, Cavenee WK, Palade GE (1998): Host microvasculature influence on tumor vascular morphology and endothelial gene expression. Am J Pathol, 153, 1239 –1248.
• Salamonsen LA, Woolley DE (1999): The role of proteinases in implanation. Rev Reprod, 4, 11-22.
• Salker M, Teklenburg G, Molokhia M, Lavery S, Trew G, Aojanepong T, Mardon HJ, Lokugamage AU, Rai R, Landles C (2010): Natural selection of human embryos: impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss. PLoS One, 5:e10287.
• Shaw JL, Denison FC, Evans J, Durno K, Williams AR, Entrican G, Critchley HO, Jabbour HN, Horne AW (2010): Evidence of prokineticin dysregulation in fallopian tube from women with ectopic pregnancy. Fertil Steril, 94, 1601–1608.
• Stewart PA, Wiley M J (1981): Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail-chick transplantation chimeras. Dev Biol, 84, 183–192.
• Su MT, Lin SH, Lee IW, Chen YC, Hsu CC, Pan HA, Kuo PL (2010): Polymorphisms of endocrine gland-derived vascular endothelial growth factor gene and its receptor genes are associated with recurrent pregnancy loss. Hum Reprod, 25, 2923–2930.
• Traboulsi W, Brouillet S, Sergent F, Boufettal H, Samouh N, Aboussaouira T, Hoffmann P, Feige JJ, Benharouga M, Alfaidy N (2015): Prokineticins in central and peripheral control of human reproduction. Horm Mol Biol Clin Investig, 24(2), 73-81.
• Waddell JM, Evans J, Jabbour HN, Denison FC (2011): CTGF expression is up-regulated by PROK1 in early pregnancy and influences HTR-8/ Svneo cell adhesion and network formation. Hum Reprod, 26(1), 67-75.
• Wang H, Li Q, Shao L, Zhu C (2001): Expression of matrix metalloproteinase -2, -9, -14, and Tissue inhibitors of metalloproteinase -1, -2, -3 in the endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy. Biol Reprod, 65, 31-40.