Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Spatiotemporal expression profile of proteases and immunological, angiogenic, hormonal and apoptotic mediators in rat placenta before and during intrauterine trophoblast migration

Juneo F. Silva A , Natália M. Ocarino B and Rogéria Serakides B C

A Laboratório de Histologia Animal, Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Campus Soane Nazaré de Andrade, Rodovia Jorge Amado, Km 16, 45662-900, Ilhéus, Bahia, Brazil.

B Laboratório de Patologia, Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Campus Pampulha, Avenida Antônio Carlos, 31270-901, Belo Horizonte, Minas Gerais, Brazil.

C Corresponding author. Email: serakidesufmg@gmail.com

Reproduction, Fertility and Development - https://doi.org/10.1071/RD16280
Submitted: 14 July 2016  Accepted: 19 September 2016   Published online: 14 October 2016

Abstract

The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated. In addition, the expression of the Vegf, Flk1, placental growth factor (Pigf), soluble fms-like tyrosine kinase 1 (sFlt1), placental lactogen 1 (Pl1), proliferin-related protein (rPlf), placental leptin (Lep), Toll-like receptor 2 (Tlr2), Toll-like receptor 4 (Tlr4), Infg, Mif, tumour necrosis factor-α (Tnf), interleukin-10 (Il10), Nos2, caspase 3 (Casp3), Bax, Bcl2, matrix metalloproteinase 2 (Mmp2) and matrix metalloproteinase 9 (Mmp9) genes was determined by real-time reverse transcription–polymerase chain reaction. At 10 days gestation, gene expression of Tlr2, Tlr4, Tnf, Infg, Il10, Casp3, Pigf, sFlt1 and Lep (P < 0.05) were higher than at 14 and/or 19 days of gestation. The beginning of intrauterine trophoblast invasion, i.e., at 14 days of gestation, coincided with higher gene and/or protein expression of MMP9, VEGF, Flk1, NOS2, MIF, BAX and rPlf compared to days 10 and 19 (P < 0.05). In contrast, gene expression of Mmp2 and Pl1 was higher at the end of trophoblast invasion compared to 10 and 14 days of gestation (P < 0.05). In conclusion, before intrauterine trophoblast migration, expression of TLRs and immunological and pro-apoptotic mediators is higher, whereas the beginning of trophoblast migration is characterised by higher expression of the pro-angiogenic factors NOS2 and MMP9. In contrast, MMP2 and PL1 expression is higher at the end of intrauterine trophoblast migration.

Additional keywords: cytokines, factors, lactogenic, rodent, trophoblastic invasion, vascular.


References

Ahmed, A., Dunk, C., Ahmad, S., and Khaliq, A. (2000). Regulation of placental vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) and soluble Flt-1 by oxygen: a review. Placenta 21, S16–S24.
Regulation of placental vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) and soluble Flt-1 by oxygen: a review.CrossRef | 10831117PubMed | open url image1

Amin, M. A., Volpert, O. V., Woods, J. M., Kumar, P., Harlow, L. A., and Koch, A. E. (2003). Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase. Circ. Res. 93, 321–329.
Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase.CrossRef | 1:CAS:528:DC%2BD3sXmt1Ohs7w%3D&md5=70f7930cdb165eadfa2595fc269d60d9CAS | 12881477PubMed | open url image1

Andraweera, P. H., Dekker, G. A., and Roberts, C. T. (2012). The vascular endothelial growth factor family in adverse pregnancy outcomes. Hum. Reprod. Update 18, 436–457.
The vascular endothelial growth factor family in adverse pregnancy outcomes.CrossRef | 1:CAS:528:DC%2BC38XptVGktLw%3D&md5=520818f6a5c7e30ba30a2675d4d42e57CAS | 22495259PubMed | open url image1

Ashkar, A. A., Di Santo, J. P., and Croy, B. A. (2000). Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J. Exp. Med. 192, 259–270.
Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy.CrossRef | 1:CAS:528:DC%2BD3cXkvFGiu7o%3D&md5=f8ab4c6af64fb787e40656db2add4e70CAS | 10899912PubMed | open url image1

Bevilacqua, E., and Abrahamsohn, P. A. (1994). Invasiveness of mouse trophoblastic cells in connective tissue. Acta Anat. (Basel) 150, 246–252.
Invasiveness of mouse trophoblastic cells in connective tissue.CrossRef | 1:STN:280:DyaK2M7ktFOmsg%3D%3D&md5=aa02c9b32c900fe9a7d9575885bf2e13CAS | 7839792PubMed | open url image1

Burton, G. J., and Jaunaiux, E. (2001). Maternal vascularisation of the human placenta: does the embryo develop in a hypoxic environment? Gynecol. Obstet. Fertil. 29, 503–508.
Maternal vascularisation of the human placenta: does the embryo develop in a hypoxic environment?CrossRef | 1:STN:280:DC%2BD3MrivFeqsA%3D%3D&md5=a08fa828cfe6f4665e6294c2f25fbe0bCAS | 11575145PubMed | open url image1

Caluwaerts, S., Vercruysse, L., Luyten, C., and Pijnenborg, R. (2005). Endovascular trophoblast invasion and associated structural changes in uterine spiral arteries of the pregnant rat. Placenta 26, 574–584.
Endovascular trophoblast invasion and associated structural changes in uterine spiral arteries of the pregnant rat.CrossRef | 1:CAS:528:DC%2BD2MXlvFKls7o%3D&md5=9f71cd4821bc5aee6b88bcd92d258eaaCAS | 15993707PubMed | open url image1

Cardaropoli, S., Paulesu, L., Romagnoli, R., Ietta, F., Marzioni, D., Castellucci, M., Rolfo, A., Vasario, E., Piccoli, E., and Todros, T. (2012). Macrophage migration inhibitory factor in fetoplacental tissues from preeclamptic pregnancies with or without fetal growth restriction. Clin. Dev. Immunol. 2012, 639342.
Macrophage migration inhibitory factor in fetoplacental tissues from preeclamptic pregnancies with or without fetal growth restriction.CrossRef | 22007254PubMed | open url image1

Cartwright, J. E., Holden, D. P., and Whitley, G. S. (1999). Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide. Br. J. Pharmacol. 128, 181–189.
Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide.CrossRef | 1:CAS:528:DyaK1MXmt1Wjsrk%3D&md5=2422d73a1a69663ce7ac08994a9677adCAS | 10498850PubMed | open url image1

Chakraborty, D., Rumi, M. A., Konno, T., and Soares, M. J. (2011). Natural killer cells direct hemochorial placentation by regulating hypoxia-inducible factor dependent trophoblast lineage decisions. Proc. Natl Acad. Sci. USA 108, 16 295–16 300.
Natural killer cells direct hemochorial placentation by regulating hypoxia-inducible factor dependent trophoblast lineage decisions.CrossRef | 1:CAS:528:DC%2BC3MXht1Kmtb%2FF&md5=09c265b1de857795f0ac563e3f7d52eeCAS | open url image1

Corbacho, A. M., Martinez De La Escalera, G., and Clapp, C. (2002). Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis. J. Endocrinol. 173, 219–238.
Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis.CrossRef | 1:CAS:528:DC%2BD38Xkt1SlsLw%3D&md5=0732f0152c8b7cd5fd3dcc985d4b26c7CAS | 12010630PubMed | open url image1

Coulam, C. B. (2000). Understanding the immunobiology of pregnancy and applying it to treatment of recurrent pregnancy loss. Early Pregnancy 4, 19–29.
| 1:CAS:528:DC%2BD3MXntlegt7w%3D&md5=195452c13845e0c78a528d0ade515b76CAS | 11719819PubMed | open url image1

Cross, J. C. (2005). How to make a placenta: mechanisms of trophoblast cell differentiation in mice: a review. Placenta 26, S3–S9.
How to make a placenta: mechanisms of trophoblast cell differentiation in mice: a review.CrossRef | 15837063PubMed | open url image1

Cross, J. C., Anson-Cartwright, L., and Scott, I. C. (2002a). Transcription factors underlying the development and endocrine functions of the placenta. Recent Prog. Horm. Res. 57, 221–234.
Transcription factors underlying the development and endocrine functions of the placenta.CrossRef | 1:CAS:528:DC%2BD38Xjt1WqtL8%3D&md5=ef1994a9b8563f444aa5bd1e77ee0b14CAS | 12017545PubMed | open url image1

Cross, J. C., Hemberger, M., Lu, Y., Nozaki, T., Whiteley, K., Masutani, M., and Adamson, S. L. (2002b). Trophoblast functions, angiogenesis and remodeling of the maternal vasculature in the placenta. Mol. Cell. Endocrinol. 187, 207–212.
Trophoblast functions, angiogenesis and remodeling of the maternal vasculature in the placenta.CrossRef | 1:CAS:528:DC%2BD38Xjt1Sqt78%3D&md5=b69c42339f537667754bf2af34046da3CAS | 11988329PubMed | open url image1

Erboga, M., and Kanter, M. (2015). Trophoblast cell proliferation and apoptosis in placental development during early gestation period in rats. Anal. Quant. Cytopathol. Histpathol. 37, 286–294.
| 26856113PubMed | open url image1

Faria, M. R., Hoshida, M. S., Ferro, E. A., Ietta, F., Paulesu, L., and Bevilacqua, E. (2010). Spatiotemporal patterns of macrophage migration inhibitory factor (Mif) expression in the mouse placenta. Reprod. Biol. Endocrinol. 8, 95.
Spatiotemporal patterns of macrophage migration inhibitory factor (Mif) expression in the mouse placenta.CrossRef | 20684790PubMed | open url image1

Flo, T. H., Ryan, L., Latz, E., Takeuchi, O., Monks, B. G., Lien, E., Halaas, O., Akira, S., Skjak-Braek, G., Golenbock, D. T., and Espevik, T. (2002). Involvement of toll-like receptor (TLR) 2 and TLR4 in cell activation by mannuronic acid polymers. J. Biol. Chem. 277, 35 489–35 495.
Involvement of toll-like receptor (TLR) 2 and TLR4 in cell activation by mannuronic acid polymers.CrossRef | 1:CAS:528:DC%2BD38Xnt1Wmtbw%3D&md5=b03bfc7d388bbdc485ea81607f26c63fCAS | open url image1

Gambino, Y. P., Maymo, J. L., Perez-Perez, A., Duenas, J. L., Sanchez-Margalet, V., Calvo, J. C., and Varone, C. L. (2010). 17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions. Biol. Reprod. 83, 42–51.
17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions.CrossRef | 1:CAS:528:DC%2BC3cXotlWqtL0%3D&md5=3cfeb9378f71c3928c080ae3c8fb8ad3CAS | 20237333PubMed | open url image1

Gambino, Y. P., Maymo, J. L., Perez Perez, A., Calvo, J. C., Sanchez-Margalet, V., and Varone, C. L. (2012). Elsevier Trophoblast Research Award Lecture: molecular mechanisms underlying estrogen functions in trophoblastic cells–focus on leptin expression. Placenta 33, S63–S70.
Elsevier Trophoblast Research Award Lecture: molecular mechanisms underlying estrogen functions in trophoblastic cells–focus on leptin expression.CrossRef | 22197627PubMed | open url image1

Giannice, R., Erreni, M., Allavena, P., Buscaglia, M., and Tozzi, R. (2013). Chemokines mRNA expression in relation to the macrophage migration inhibitory factor (MIF) mRNA and vascular endothelial growth factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: a pilot study. Cytokine 64, 509–515.
Chemokines mRNA expression in relation to the macrophage migration inhibitory factor (MIF) mRNA and vascular endothelial growth factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: a pilot study.CrossRef | 1:CAS:528:DC%2BC3sXhtlCgt7zI&md5=ed8e640b90670bb8d27b4e326454160eCAS | 23985752PubMed | open url image1

Goedbloed, J. F. (1976). Embryonic and postnatal growth of rat and mouse. IV. Prenatal growth of organs and tissues: age determination, and general growth pattern. Acta Anat. (Basel) 95, 8–33.
Embryonic and postnatal growth of rat and mouse. IV. Prenatal growth of organs and tissues: age determination, and general growth pattern.CrossRef | 1:STN:280:DyaE283kvFCjtQ%3D%3D&md5=57af544f9b955dce10a3c69e35457f98CAS | 952201PubMed | open url image1

Hammer, A. (2011). Immunological regulation of trophoblast invasion. J. Reprod. Immunol. 90, 21–28.
Immunological regulation of trophoblast invasion.CrossRef | 1:CAS:528:DC%2BC3MXos1ygsLc%3D&md5=1c8dd479d7f9f73ee7116b7d20f3a45bCAS | 21641660PubMed | open url image1

He, H., Venema, V. J., Gu, X., Venema, R. C., Marrero, M. B., and Caldwell, R. B. (1999). Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J. Biol. Chem. 274, 25 130–25 135.
Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src.CrossRef | 1:CAS:528:DyaK1MXls1ymu70%3D&md5=d6da80ef46d69da4433724bd90ef0944CAS | open url image1

Hemberger, M., Nozaki, T., Masutani, M., and Cross, J. C. (2003). Differential expression of angiogenic and vasodilatory factors by invasive trophoblast giant cells depending on depth of invasion. Dev. Dyn. 227, 185–191.
Differential expression of angiogenic and vasodilatory factors by invasive trophoblast giant cells depending on depth of invasion.CrossRef | 1:CAS:528:DC%2BD3sXltlKjtro%3D&md5=53a898e7b7d2e4583dc90574d54f085cCAS | 12761846PubMed | open url image1

Hu, D., and Cross, J. C. (2010). Development and function of trophoblast giant cells in the rodent placenta. Int. J. Dev. Biol. 54, 341–354.
Development and function of trophoblast giant cells in the rodent placenta.CrossRef | 1:CAS:528:DC%2BC3cXltVajtbg%3D&md5=3e023f2ff2d4b4eb222ed771e10a365cCAS | 19876834PubMed | open url image1

Huang, Y. Y., Yao, X. B., Lu, X. H., Liu, H. S., and Chen, D. J. (2009). [Relationship between changes of endogenous nitric oxide synthase inhibitor and hydrolase and initiation of pre-eclampsia.] Zhonghua Fu Chan Ke Za Zhi 44, 249–252.
| 1:CAS:528:DC%2BD1MXot1ent7c%3D&md5=cd786673c0d8d220fd977d5048a7f607CAS | 19570459PubMed | open url image1

Hunt, J. S., Atherton, R. A., and Pace, J. L. (1990). Differential responses of rat trophoblast cells and embryonic fibroblasts to cytokines that regulate proliferation and class I MHC antigen expression. J. Immunol. 145, 184–189.
| 1:CAS:528:DyaK3cXltlSgtbk%3D&md5=4ac4a7ed9922ca367846479d6cca2cfaCAS | 2113554PubMed | open url image1

Hunt, J. S., Chen, H. L., and Miller, L. (1996). Tumor necrosis factors: pivotal components of pregnancy? Biol. Reprod. 54, 554–562.
Tumor necrosis factors: pivotal components of pregnancy?CrossRef | 1:CAS:528:DyaK28XhtFCjt70%3D&md5=656a33888a3b2d99d18480001d015ab4CAS | 8835376PubMed | open url image1

Jackson, D., Volpert, O. V., Bouck, N., and Linzer, D. I. (1994). Stimulation and inhibition of angiogenesis by placental proliferin and proliferin-related protein. Science 266, 1581–1584.
Stimulation and inhibition of angiogenesis by placental proliferin and proliferin-related protein.CrossRef | 1:CAS:528:DyaK2MXisVGlsrc%3D&md5=db6eb5d8e84f86b06e5f6c350a5ce20aCAS | 7527157PubMed | open url image1

Jovanović Krivokuća, M., Stefanoska, I., Abu Rabi, T., Al-Abed, Y., Stošić-Grujičić, S., and Vićovac, L. (2015). Pharmacological inhibition of MIF interferes with trophoblast cell migration and invasiveness. Placenta 36, 150–159.
Pharmacological inhibition of MIF interferes with trophoblast cell migration and invasiveness.CrossRef | 25530499PubMed | open url image1

Kaufmann, P., Black, S., and Huppertz, B. (2003). Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol. Reprod. 69, 1–7.
Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia.CrossRef | 1:CAS:528:DC%2BD3sXkvFCnsbY%3D&md5=c7838723937192a0e3a8e73128783a06CAS | 12620937PubMed | open url image1

Khaliq, A., Dunk, C., Jiang, J., Shams, M., Li, X. F., Acevedo, C., Weich, H., Whittle, M., and Ahmed, A. (1999). Hypoxia down-regulates placenta growth factor, whereas fetal growth restriction up-regulates placenta growth factor expression: molecular evidence for ‘placental hyperoxia’ in intrauterine growth restriction. Lab. Invest. 79, 151–170.
| 1:CAS:528:DyaK1MXhsl2juro%3D&md5=81ef0cae4db6496993938a49cc94fbc7CAS | 10068204PubMed | open url image1

Kim, S., Lee, D. S., Watanabe, K., Furuoka, H., Suzuki, H., and Watarai, M. (2005). Interferon-gamma promotes abortion due to Brucella infection in pregnant mice. BMC Microbiol. 5, 22.
Interferon-gamma promotes abortion due to Brucella infection in pregnant mice.CrossRef | 15869716PubMed | open url image1

Knöfler, M. (2010). Critical growth factors and signalling pathways controlling human trophoblast invasion. Int. J. Dev. Biol. 54, 269–280.
Critical growth factors and signalling pathways controlling human trophoblast invasion.CrossRef | 19876833PubMed | open url image1

Koga, K., Aldo, P. B., and Mor, G. (2009). Toll-like receptors and pregnancy: trophoblast as modulators of the immune response. J. Obstet. Gynaecol. Res. 35, 191–202.
Toll-like receptors and pregnancy: trophoblast as modulators of the immune response.CrossRef | 1:CAS:528:DC%2BD1MXls1yqs7w%3D&md5=b602bf4b86adac48c6a460c7b173b586CAS | 19335792PubMed | open url image1

Lala, P. K., and Chakraborty, C. (2003). Factors regulating trophoblast migration and invasiveness: possible derangements contributing to pre-eclampsia and fetal injury. Placenta 24, 575–587.
Factors regulating trophoblast migration and invasiveness: possible derangements contributing to pre-eclampsia and fetal injury.CrossRef | 1:CAS:528:DC%2BD3sXkvVejsbs%3D&md5=183a43bc7035e514d33765733f77af86CAS | 12828917PubMed | open url image1

Lash, G. E., Otun, H. A., Innes, B. A., Kirkley, M., De Oliveira, L., Searle, R. F., Robson, S. C., and Bulmer, J. N. (2006). Interferon-gamma inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels. FASEB J. 20, 2512–2518.
Interferon-gamma inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels.CrossRef | 1:CAS:528:DC%2BD28Xht1OmsLbL&md5=91ba264df230ec67aa154072796bd76dCAS | 17142800PubMed | open url image1

Lea, R. G., Riley, S. C., Antipatis, C., Hannah, L., Ashworth, C. J., Clark, D. A., and Critchley, H. O. (1999). Cytokines and the regulation of apoptosis in reproductive tissues: a review. Am. J. Reprod. Immunol. 42, 100–109.
| 1:STN:280:DyaK1MvgsVensA%3D%3D&md5=aae1d0042195cb143527a81f6d07ca95CAS | 10476692PubMed | open url image1

Lunghi, L., Ferretti, M. E., Medici, S., Biondi, C., and Vesce, F. (2007). Control of human trophoblast function. Reprod. Biol. Endocrinol. 5, 6.
Control of human trophoblast function.CrossRef | 17288592PubMed | open url image1

Lyall, F., Bulmer, J. N., Kelly, H., Duffie, E., and Robson, S. C. (1999). Human trophoblast invasion and spiral artery transformation: the role of nitric oxide. Am. J. Pathol. 154, 1105–1114.
Human trophoblast invasion and spiral artery transformation: the role of nitric oxide.CrossRef | 1:CAS:528:DyaK1MXislKrs7s%3D&md5=8b53837a7539446ad7eeafc8071a962eCAS | 10233849PubMed | open url image1

Maynard, S. E., Min, J. Y., Merchan, J., Lim, K. H., Li, J., Mondal, S., Libermann, T. A., Morgan, J. P., Sellke, F. W., Stillman, I. E., Epstein, F. H., Sukhatme, V. P., and Karumanchi, S. A. (2003). Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J. Clin. Invest. 111, 649–658.
Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.CrossRef | 1:CAS:528:DC%2BD3sXhvFentbc%3D&md5=eddd7f8c3636359b1950f4060b23381aCAS | 12618519PubMed | open url image1

Nothnick, W. B., Colvin, A., Cheng, K. F., and Al-Abed, Y. (2011). Inhibition of macrophage migration inhibitory factor reduces endometriotic implant size in mice with experimentally induced disease. J. Endometr. 3, 135–142.
| 24790725PubMed | open url image1

Pavan, L., Tarrade, A., Hermouet, A., Delouis, C., Titeux, M., Vidaud, M., Therond, P., Evain-Brion, D., and Fournier, T. (2003). Human invasive trophoblasts transformed with simian virus 40 provide a new tool to study the role of PPARgamma in cell invasion process. Carcinogenesis 24, 1325–1336.
Human invasive trophoblasts transformed with simian virus 40 provide a new tool to study the role of PPARgamma in cell invasion process.CrossRef | 1:CAS:528:DC%2BD3sXmtFKktbs%3D&md5=1307691eb2801df6a8de4abedceef21fCAS | 12807721PubMed | open url image1

Pijnenborg, R., Robertson, W. B., Brosens, I., and Dixon, G. (1981). Review article: trophoblast invasion and the establishment of haemochorial placentation in man and laboratory animals. Placenta 2, 71–91.
Review article: trophoblast invasion and the establishment of haemochorial placentation in man and laboratory animals.CrossRef | 1:STN:280:DyaL3M7ltV2isw%3D%3D&md5=29ca54f6d3afc3cfc490f3f29a21a3aeCAS | 7010344PubMed | open url image1

Plaisier, M., Rodrigues, S., Willems, F., Koolwijk, P., van Hinsbergh, V. W., and Helmerhorst, F. M. (2007). Different degrees of vascularization and their relationship to the expression of vascular endothelial growth factor, placental growth factor, angiopoietins, and their receptors in first-trimester decidual tissues. Fertil. Steril. 88, 176–187.
Different degrees of vascularization and their relationship to the expression of vascular endothelial growth factor, placental growth factor, angiopoietins, and their receptors in first-trimester decidual tissues.CrossRef | 1:CAS:528:DC%2BD2sXptFGks7c%3D&md5=bea4a6c8cfffbe75f5c84c4b91aff2a5CAS | 17383647PubMed | open url image1

Plaisier, M., Dennert, I., Rost, E., Koolwijk, P., van Hinsbergh, V. W., and Helmerhorst, F. M. (2009). Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum. Reprod. 24, 185–197.
Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions.CrossRef | 1:CAS:528:DC%2BD1cXhsFWjtbbK&md5=702a501304fe7b365c063897201f1e66CAS | 18854409PubMed | open url image1

Rosario, G. X., Konno, T., and Soares, M. J. (2008). Maternal hypoxia activates endovascular trophoblast cell invasion. Dev. Biol. 314, 362–375.
Maternal hypoxia activates endovascular trophoblast cell invasion.CrossRef | 1:CAS:528:DC%2BD1cXhslKqtLo%3D&md5=2cd372976e5aee7915b8b0c598c3001cCAS | 18199431PubMed | open url image1

Roth, I., and Fisher, S. J. (1999). IL-10 is an autocrine inhibitor of human placental cytotrophoblast MMP-9 production and invasion. Dev. Biol. 205, 194–204.
IL-10 is an autocrine inhibitor of human placental cytotrophoblast MMP-9 production and invasion.CrossRef | 1:CAS:528:DyaK1MXmslCitQ%3D%3D&md5=b26fe6061cd1d185576e2f3ab6c546d0CAS | 9882507PubMed | open url image1

Silva, J. F., and Serakides, R. (2016). Intrauterine trophoblast migration: a comparative view of humans and rodents. Cell Adh. Migr. 10, 88–110.
Intrauterine trophoblast migration: a comparative view of humans and rodents.CrossRef | 1:CAS:528:DC%2BC28XisVCqsbc%3D&md5=898162b86debf97aefe00c332bad6004CAS | 26743330PubMed | open url image1

Silva, J. F., Ocarino, N. M., and Serakides, R. (2014). Maternal thyroid dysfunction affects placental profile of inflammatory mediators and the intrauterine trophoblast migration kinetics. Reproduction 147, 803–816.
Maternal thyroid dysfunction affects placental profile of inflammatory mediators and the intrauterine trophoblast migration kinetics.CrossRef | 1:CAS:528:DC%2BC2cXhtVKjurjO&md5=a8e0c1781056a168a573b67ce28ff290CAS | 24534949PubMed | open url image1

Silva, J. F., Vidigal, P. N., Galvao, D. D., Boeloni, J. N., Nunes, P. P., Ocarino, N. M., Nascimento, E. F., and Serakides, R. (2012). Fetal growth restriction in hypothyroidism is associated with changes in proliferative activity, apoptosis and vascularisation of the placenta. Reprod. Fertil. Dev. 24, 923–931.
Fetal growth restriction in hypothyroidism is associated with changes in proliferative activity, apoptosis and vascularisation of the placenta.CrossRef | 22935153PubMed | open url image1

Simon, M. C., and Keith, B. (2008). The role of oxygen availability in embryonic development and stem cell function. Nat. Rev. Mol. Cell Biol. 9, 285–296.
The role of oxygen availability in embryonic development and stem cell function.CrossRef | 1:CAS:528:DC%2BD1cXjsFCksbk%3D&md5=613b01b68bb6e8b2ce218f70e6f14c3aCAS | 18285802PubMed | open url image1

Siwetz, M., Blaschitz, A., El-Heliebi, A., Hiden, U., Desoye, G., Huppertz, B., and Gauster, M. (2016). TNF-alpha alters the inflammatory secretion profile of human first trimester placenta. Lab. Invest. 96, 428–438.
TNF-alpha alters the inflammatory secretion profile of human first trimester placenta.CrossRef | 1:CAS:528:DC%2BC28XhtV2ru7g%3D&md5=72b5db5d442c80269c615ae94a941d03CAS | 26752743PubMed | open url image1

Smith, S. K., He, Y., Clark, D. E., and Charnock-Jones, D. S. (2000). Angiogenic growth factor expression in placenta. Semin. Perinatol. 24, 82–86.
Angiogenic growth factor expression in placenta.CrossRef | 1:STN:280:DC%2BD3c7ntlWjsw%3D%3D&md5=8a1b9ab2d197809a92a9726ac2a68823CAS | 10709867PubMed | open url image1

Soares, M. J., Chakraborty, D., Karim Rumi, M. A., Konno, T., and Renaud, S. J. (2012). Rat placentation: an experimental model for investigating the hemochorial maternal–fetal interface. Placenta 33, 233–243.
Rat placentation: an experimental model for investigating the hemochorial maternal–fetal interface.CrossRef | 1:STN:280:DC%2BC383lvVOmtg%3D%3D&md5=a99dab489c181483c3980a2a1a06ce5aCAS | 22284666PubMed | open url image1

Sorenson, R. L., and Brelje, T. C. (1997). Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm. Metab. Res. 29, 301–307.
Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones.CrossRef | 1:CAS:528:DyaK2sXltV2ruro%3D&md5=72674293fb774101c2e61b75ccbf27d0CAS | 9230352PubMed | open url image1

Takeda, K., and Akira, S. (2001). Regulation of innate immune responses by Toll-like receptors. Jpn. J. Infect. Dis. 54, 209–219.
| 1:CAS:528:DC%2BD38Xjtlyrs78%3D&md5=e1fc740be259543d0acb3a82194b8053CAS | 11862002PubMed | open url image1

Tarrade, A., Schoonjans, K., Pavan, L., Auwerx, J., Rochette-Egly, C., Evain-Brion, D., and Fournier, T. (2001). PPARgamma/RXRalpha heterodimers control human trophoblast invasion. J. Clin. Endocrinol. Metab. 86, 5017–5024.
| 1:CAS:528:DC%2BD3MXptVartLw%3D&md5=25699f3dd5897507ae3ff1ef4c6d4ba1CAS | 11600579PubMed | open url image1

Thaxton, J. E., and Sharma, S. (2010). Interleukin-10: a multi-faceted agent of pregnancy. Am. J. Reprod. Immunol. 63, 482–491.
Interleukin-10: a multi-faceted agent of pregnancy.CrossRef | 1:CAS:528:DC%2BC3cXot1KjtL8%3D&md5=5f8be1fed2bb639d8d5d9dae8b86858fCAS | 20163400PubMed | open url image1

Toder, V., Fein, A., Carp, H., and Torchinsky, A. (2003). TNF-alpha in pregnancy loss and embryo maldevelopment: a mediator of detrimental stimuli or a protector of the fetoplacental unit? J. Assist. Reprod. Genet. 20, 73–81.
TNF-alpha in pregnancy loss and embryo maldevelopment: a mediator of detrimental stimuli or a protector of the fetoplacental unit?CrossRef | 1:STN:280:DC%2BD3s7ntVSmtg%3D%3D&md5=45ad2bb105d3b49d3d21e686b7c3f300CAS | 12688591PubMed | open url image1

Toft, D. J., and Linzer, D. I. (2000). Identification of three prolactin-related hormones as markers of invasive trophoblasts in the rat. Biol. Reprod. 63, 519–525.
Identification of three prolactin-related hormones as markers of invasive trophoblasts in the rat.CrossRef | 1:CAS:528:DC%2BD3cXltl2gtb0%3D&md5=6e8ec2d3e86024e726167c40011257ecCAS | 10906059PubMed | open url image1

Varanou, A., Withington, S. L., Lakasing, L., Williamson, C., Burton, G. J., and Hemberger, M. (2006). The importance of cysteine cathepsin proteases for placental development. J. Mol. Med. (Berl) 84, 305–317.
The importance of cysteine cathepsin proteases for placental development.CrossRef | 1:CAS:528:DC%2BD28XjtVSms7Y%3D&md5=653a5c4a0e57e4d176ddcaf5b83d7054CAS | 16440214PubMed | open url image1

Veillat, V., Carli, C., Metz, C. N., Al-Abed, Y., Naccache, P. H., and Akoum, A. (2010). Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways. J. Clin. Endocrinol. Metab. 95, E403–E412.
Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways.CrossRef | 1:CAS:528:DC%2BC3cXhs1arsLbK&md5=9081c2dfb1635a9b841d8362df2dd6dbCAS | 20829186PubMed | open url image1

Vercruysse, L., Caluwaerts, S., Luyten, C., and Pijnenborg, R. (2006). Interstitial trophoblast invasion in the decidua and mesometrial triangle during the last third of pregnancy in the rat. Placenta 27, 22–33.
Interstitial trophoblast invasion in the decidua and mesometrial triangle during the last third of pregnancy in the rat.CrossRef | 1:CAS:528:DC%2BD2MXht1GhsrjP&md5=1438c958e871b137885c548ededdd0bfCAS | 16310034PubMed | open url image1

Viganò, P., Cintorino, M., Schatz, F., Lockwood, C. J., and Arcuri, F. (2007). The role of macrophage migration inhibitory factor in maintaining the immune privilege at the fetal–maternal interface. Semin. Immunopathol. 29, 135–150.
The role of macrophage migration inhibitory factor in maintaining the immune privilege at the fetal–maternal interface.CrossRef | 17621699PubMed | open url image1

Vuorela, P., Hatva, E., Lymboussaki, A., Kaipainen, A., Joukov, V., Persico, M. G., Alitalo, K., and Halmesmaki, E. (1997). Expression of vascular endothelial growth factor and placenta growth factor in human placenta. Biol. Reprod. 56, 489–494.
Expression of vascular endothelial growth factor and placenta growth factor in human placenta.CrossRef | 1:CAS:528:DyaK2sXos1ertQ%3D%3D&md5=4036fa88911f4276ef3a2f5b3e048096CAS | 9116151PubMed | open url image1

Yelavarthi, K. K., Chen, H. L., Yang, Y. P., Cowley, B. D., Fishback, J. L., and Hunt, J. S. (1991). Tumor necrosis factor-alpha mRNA and protein in rat uterine and placental cells. J. Immunol. 146, 3840–3848.
| 1:CAS:528:DyaK3MXkt1Ontro%3D&md5=cd08b412ce521568cb74db793e30b021CAS | 2033253PubMed | open url image1

Zhang, L. J., Yang, M., and Ding, Y. L. (2007). [Bcl-2, TGFbeta1, and apoptosis in placenta tissues in patients with hypertensive disorder complicating pregnancy.] Zhong Nan Da Xue Xue Bao Yi Xue Ban 32, 883–889.
| 18007089PubMed | open url image1



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