Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo
Abstract
:1. Introduction
2. Results
2.1. Endometrial Transcriptome Profiling
2.2. Functional Annotation of Microarray Data
2.3. Comparison of Estradiol-17β Effect with Pregnancy-Induced Transcriptome Changes
2.4. Validation of the Microarray Results by Quantitative Real-Time RT-PCR
2.5. The Effects of E2 on PGE2 Secretion and PGF2α Metabolite (PGFM) Accumulation
3. Discussion
3.1. The Effect of Estradiol-17β on Porcine Endometrial Transcriptome In Vivo
3.2. Potential Upstream Regulators of DEGs
3.3. Validation of the Microarray Results by Quantitative PCR
3.4. Estradiol-17β Affects the Expression of Genes Involved in Secretive Function and Ion Transport in Endometrium
3.5. Estradiol-17β Affects Processes Related with Immune Response
3.6. Involvement of Estrogen Signaling in Processes Related to Cell Adhesion, Differentiation, and Proliferation and Tissue Remodeling
4. Materials and Methods
4.1. Tissue Collection
4.2. Effect of E2 on Porcine Endometrium In Vivo
4.3. RNA Isolation and cDNA Synthesis
4.4. Global Gene Expression Profiling Using Expression Microarrays
4.4.1. Functional Annotation of Microarray Data
4.4.2. Validation of Microarray Results
4.5. PGs Secretion by Endometrial Explants in Response to Estradiol-17β In Vivo
4.5.1. Isolation of Endometrial Explants
4.5.2. Measurement of Hormone Concentration in Incubation Media
4.6. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Pope, W.F.; First, N.L. Factors affecting the survival of pig embryos. Theriogenology 1985, 23, 91–105. [Google Scholar] [CrossRef]
- Waclawik, A.; Kaczmarek, M.M.; Blitek, A.; Kaczynski, P.; Ziecik, A.J. Embryo-maternal dialogue during pregnancy establishment and implantation in the pig. Mol. Reprod. Dev. 2017, 84, 842–855. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Groothuis, P.G.; Dassen, H.H.; Romano, A.; Punyadeera, C. Estrogen and the endometrium: Lessons learned from gene expression profiling in rodents and human. Hum. Reprod. Update 2007, 13, 405–417. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Waclawik, A. Novel insights into the mechanisms of pregnancy establishment: Regulation of prostaglandin synthesis and signaling in the pig. Reproduction 2011, 142, 389–399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bazer, F.W.; Thatcher, W.W. Theory of maternal recognition of pregnancy in swine based on estrogen controlled endocrine versus exocrine secretion of prostaglandin F2α by the uterine endometrium. Prostaglandins 1977, 14, 397–400. [Google Scholar] [CrossRef]
- Bolet, G. Timing and Extent of Embryonic Mortality in Pigs Sheep and Goats: Genetic Variability. In Embryonic Mortality in Farm Animals; Current Topics in Veterinary Medicine and Animal Science; Sreenan, J.M., Diskin, M.G., Eds.; Springer: Dordrecht, The Netherlands, 1986; pp. 12–43. [Google Scholar]
- Geisert, R.D.; Brenner, R.M.; Moffatt, J.; Harney, J.P.; Yellin, T.; Bazer, F.W. Changes in oestrogen receptor protein, mRNA expression and localization in the endometrium of cyclic and pregnant gilts. Reprod. Fertil. Dev. 1993, 5, 247–260. [Google Scholar] [CrossRef] [PubMed]
- Geisert, R.D.; Thatcher, W.W.; Roberts, R.M.; Bazer, F.W. Establishment of pregnancy in the pig: III. Endometrial secretory response to estradiol valerate administered on day 11 of the estrous cycle. Biol. Reprod. 1982, 27, 957–965. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bazer, F.W.; Geisert, R.D.; Thatcher, W.W.; Roberts, R.M. The establishment and maintenance of pregnancy. In Control of Pig Reproduction; Cole, D.J.A., Foxcroft, G.R., Eds.; Butterworth Scientific: London, UK, 1982; pp. 227–253. [Google Scholar]
- Laforest, J.P.; King, G.J. Structural and functional aspects of porcine endometrial capillaries on days 13 and 15 after oestrus or mating. J. Reprod. Fertil. 1992, 94, 269–277. [Google Scholar] [CrossRef] [Green Version]
- Meyer, A.E.; Pfeiffer, C.A.; Brooks, K.E.; Spate, L.D.; Benne, J.A.; Cecil, R.; Samuel, M.S.; Murphy, C.N.; Behura, S.; McLean, M.K.; et al. New perspective on conceptus estrogens in maternal recognition and pregnancy establishment in the pig. Biol. Reprod. 2019, 101, 148–161. [Google Scholar] [CrossRef]
- Østrup, E.; Bauersachs, S.; Blum, H.; Wolf, E.; Hyttel, P. Differential endometrial gene expression in pregnant and nonpregnant sows. Biol. Reprod. 2010, 83, 277–285. [Google Scholar] [CrossRef] [Green Version]
- Samborski, A.; Graf, A.; Krebs, S.; Kessler, B.; Reichenbach, M.; Reichenbach, H.D.; Ulbrich, S.E.; Bauersachs, S. Transcriptome changes in the porcine endometrium during the preattachment phase. Biol. Reprod. 2013, 89, 134. [Google Scholar] [CrossRef] [PubMed]
- Zeng, S.; Ulbrich, S.E.; Bauersachs, S. Spatial organization of endometrial gene expression at the onset of embryo attachment in pigs. BMC Genom. 2019, 20, 895. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frank, M.; Bazer, F.W.; Thatcher, W.W.; Wilcox, C.J. A study of prostaglandin F2alpha as the luteolysin in swine: III effects of estradiol valerate on prostaglandin F, progestins, estrone and estradiol concentrations in the utero-ovarian vein of nonpregnant gilts. Prostaglandins 1977, 14, 1183–1196. [Google Scholar] [CrossRef]
- Pusateri, A.E.; Smith, J.M.; Smith, J.W.; Thomford, P.J.; Diekman, M.A. Maternal recognition of pregnancy in swine. I. Minimal requirement for exogenous estradiol-17 beta to induce either short or long pseudopregnancy in cycling gilts. Biol. Reprod. 1996, 55, 582–589. [Google Scholar] [CrossRef]
- Ashworth, M.D.; Ross, J.W.; Ritchey, J.W.; Desilva, U.; Stein, D.R.; Geisert, R.D.; White, F.J. Effects of aberrant estrogen on the endometrial transcriptional profile in pigs. Reprod. Toxicol. 2012, 34, 8–15. [Google Scholar] [CrossRef]
- Samborski, A.; Graf, A.; Krebs, S.; Kessler, B.; Bauersachs, S. Deep sequencing of the porcine endometrial transcriptome on day 14 of pregnancy. Biol. Reprod. 2013, 88, 84. [Google Scholar] [CrossRef]
- Fujii, H.; Fujiwara, H.; Horie, A.; Sato, Y.; Konishi, I. Ephrin A1 induces intercellular dissociation in Ishikawa cells: Possible implication of the Eph-ephrin A system in human embryo implantation. Hum. Reprod. 2011, 26, 299–306. [Google Scholar] [CrossRef] [Green Version]
- Arvanitis, D.; Davy, A. Eph/ephrin signaling: Networks. Genes. Dev. 2008, 22, 416–429. [Google Scholar] [CrossRef] [Green Version]
- Franczak, A.; Kotwica, G. Secretion of estradiol-17beta by porcine endometrium and myometrium during early pregnancy and luteolysis. Theriogenology 2008, 69, 283–289. [Google Scholar] [CrossRef]
- Waclawik, A.; Ziecik, A.J. Differential expression of prostaglandin (PG) synthesis enzymes in conceptus during peri-implantation period and endometrial expression of carbonyl reductase/PG 9-ketoreductase in the pig. J. Endocrinol. 2007, 194, 499–510. [Google Scholar] [CrossRef] [Green Version]
- Ford, S.P.; Magness, R.R.; Farley, D.B.; Van Orden, D.E. Local and systemic effects of intrauterine estradiol-17 beta on luteal function of nonpregnant sows. J. Anim. Sci. 1982, 55, 657–664. [Google Scholar] [CrossRef] [PubMed]
- Zavy, M.T.; Bazer, F.W.; Thatcher, W.W.; Wilcox, C.J. A study of prostaglandin F2α as the luteolysin in swine: V. Comparison of prostaglandin F, progestins, estrone and estradiol in uterine flushings from pregnant and nonpregnant gilts. Prostaglandins 1980, 20, 837–851. [Google Scholar] [CrossRef]
- Waclawik, A.; Rivero-Muller, A.; Blitek, A.; Kaczmarek, M.M.; Brokken, L.J.; Watanabe, K.; Rahman, N.A.; Ziecik, A.J. Molecular cloning and spatiotemporal expression of prostaglandin F synthase and microsomal prostaglandin E synthase-1 in porcine endometrium. Endocrinology 2006, 147, 210–221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeng, S.; Bick, J.; Ulbrich, S.E.; Bauersachs, S. Cell type-specific analysis of transcriptome changes in the porcine endometrium on Day 12 of pregnancy. BMC Genom. 2018, 19, 459. [Google Scholar] [CrossRef] [PubMed]
- Seo, H.; Choi, Y.; Shim, J.; Yoo, I.; Ka, H. Prostaglandin transporters ABCC4 and SLCO2A1 in the uterine endometrium and conceptus during pregnancy in pigs. Biol. Reprod. 2014, 100, 1–10. [Google Scholar] [CrossRef]
- Waclawik, A.; Jabbour, H.N.; Blitek, A.; Ziecik, A.J. Estradiol-17beta, prostaglandin E2 (PGE2), and the PGE2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium. Endocrinology 2009, 150, 3823–3832. [Google Scholar] [CrossRef] [Green Version]
- Roberts, R.M.; Bazer, F.W. The functions of uterine secretions. J. Reprod. Fertil. 1988, 82, 875–892. [Google Scholar] [CrossRef] [Green Version]
- Berridge, M.J.; Bootman, M.D.; Roderick, H.L. Calcium signalling: Dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell. Biol. 2003, 4, 517–529. [Google Scholar] [CrossRef] [Green Version]
- Kovacs, C.S.; Kronenberg, H.M. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr. Rev. 1997, 18, 832–872. [Google Scholar] [CrossRef] [Green Version]
- Tinel, H.; Denker, H.W.; Thie, M. Calcium influx in human uterine epithelial RL95-2 cells triggers adhesiveness for trophoblast-like cells. Model studies on signalling events during embryo implantation. Mol. Hum. Reprod. 2000, 6, 1119–1130. [Google Scholar] [CrossRef] [Green Version]
- Li, H.Y.; Shen, J.T.; Chang, S.P.; Hsu, W.L.; Sung, Y.J. Calcitonin promotes outgrowth of trophoblast cells on endometrial epithelial cells: Involvement of calcium mobilization and protein kinase C activation. Placenta 2008, 29, 20–29. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Armant, D.R. Integrin-mediated adhesion and signaling during blastocyst implantation. Cells Tissues Organs 2002, 172, 190–201. [Google Scholar] [CrossRef] [PubMed]
- Hoenderop, J.G.; Nilius, B.; Bindels, R.J. Epithelial calcium channels: From identification to function and regulation. Pflugers Arch. 2003, 446, 304–308. [Google Scholar] [CrossRef] [PubMed]
- Ka, H.; Seo, H.; Kim, M.; Choi, Y.; Lee, C.K. Identification of differentially expressed genes in the uterine endometrium on day 12 of the estrous cycle and pregnancy in pigs. Mol. Reprod. Dev. 2009, 76, 75–84. [Google Scholar] [CrossRef]
- Li, S.H.; Yin, H.B.; Ren, M.R.; Wu, M.J.; Huang, X.L.; Li, J.J.; Luan, Y.P.; Wu, Y.L. TRPV5 and TRPV6 are expressed in placenta and bone tissues during pregnancy in mice. Biotech. Histochem. 2019, 94, 244–251. [Google Scholar] [CrossRef]
- Weng, Z.P.; Wang, X.M.; Qi, H.; Tao, H.; Zhang, S.P.; Ji, X.H. Effects of transient receptor potential V6 silence on proliferation and apoptosis of trophoblasts. Zhonghua Fu Chan Ke Za Zhi 2012, 47, 777–780. [Google Scholar]
- Passey, R.J.; Williams, E.; Lichanska, A.M.; Wells, C.; Hu, S.; Geczy, C.L.; Little, M.H.; Hume, D.A. A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo. J. Immunol. 1999, 163, 2209–2216. [Google Scholar]
- Hubert, R.S.; Vivanco, I.; Chen, E.; Rastegar, S.; Leong, K.; Mitchell, S.C.; Madraswala, R.; Zhou, Y.; Kuo, J.; Raitano, A.B.; et al. STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors. Proc. Natl. Acad. Sci. USA 1999, 96, 14523–14528. [Google Scholar] [CrossRef] [Green Version]
- Yamamoto, T.; Tamura, Y.; Kobayashi, J.; Kamiguchi, K.; Hirohashi, Y.; Miyazaki, A.; Torigoe, T.; Asanuma, H.; Hiratsuka, H.; Sato, N. Six-transmembrane epithelial antigen of the prostate-1 plays a role for in vivo tumor growth via intercellular communication. Exp. Cell. Res. 2013, 319, 2617–2626. [Google Scholar] [CrossRef]
- Ng, Y.H.; Rome, S.; Jalabert, A.; Forterre, A.; Singh, H.; Hincks, C.L.; Salamonsen, L.A. Endometrial exosomes/microvesicles in the uterine microenvironment: A new paradigm for embryo-endometrial cross talk at implantation. PLoS ONE 2013, 8, e58502. [Google Scholar] [CrossRef] [Green Version]
- Ruiz-González, I.; Xu, J.; Wang, X.; Burghardt, R.C.; Dunlap, K.A.; Bazer, F.W. Exosomes, endogenous retroviruses and toll-like receptors: Pregnancy recognition in ewes. Reproduction 2015, 149, 281–291. [Google Scholar] [CrossRef] [PubMed]
- Burns, G.W.; Brooks, K.E.; O’Neil, E.V.; Hagen, D.E.; Behura, S.K.; Spencer, T.E. Progesterone effects on extracellular vesicles in the sheep uterus. Biol. Reprod. 2018, 98, 612–622. [Google Scholar] [CrossRef] [PubMed]
- Ross, J.W.; Ashworth, M.D.; Stein, D.R.; Couture, O.P.; Tuggle, C.K.; Geisert, R.D. Identification of differential gene expression during porcine conceptus rapid trophoblastic elongation and attachment to uterine luminal epithelium. Physiol. Genom. 2009, 36, 140–148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Geisert, R.D.; Lucy, M.C.; Whyte, J.J.; Ross, J.W.; Mathew, D.J. Cytokines from the pig conceptus: Roles in conceptus development in pigs. J. Anim. Sci. Biotechnol. 2014, 5, 51. [Google Scholar] [CrossRef] [Green Version]
- Davoodi, S.; Cooke, R.F.; Fernandes, A.C.; Cappellozza, B.I.; Vasconcelos, J.L.; Cerri, R.L. Expression of estrus modifies the gene expression profile in reproductive tissues on Day 19 of gestation in beef cows. Theriogenology 2016, 85, 645–655. [Google Scholar] [CrossRef]
- Zhang, X.; Hoang, E.; Nothnick, W.B. Estrogen-induced uterine abnormalities in TIMP-1 deficient mice are associated with elevated plasmin activity and reduced expression of the novel uterine plasmin protease inhibitor serpinb7. Mol. Reprod. Dev. 2009, 76, 160–172. [Google Scholar] [CrossRef] [Green Version]
- Dhanoa, B.S.; Cogliati, T.; Satish, A.G.; Bruford, E.A.; Friedman, J.S. Update on the Kelch-like (KLHL) gene family. Hum. Genom. 2013, 7, 13. [Google Scholar] [CrossRef] [Green Version]
- Perez-Torrado, R.; Yamada, D.; Defossez, P.A. Born to bind: The BTB protein-protein interaction domain. Bioessays 2006, 28, 1194–1202. [Google Scholar] [CrossRef]
- Kang, M.I.; Kobayashi, A.; Wakabayashi, N.; Kim, S.G.; Yamamoto, M. Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. PNAS 2004, 101, 2046–2051. [Google Scholar] [CrossRef] [Green Version]
- Minor, D.L.; Lin, Y.F.; Mobley, B.C.; Avelar, A.; Jan, Y.N.; Jan, L.Y.; Berger, J.M. The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel. Cell 2000, 102, 657–670. [Google Scholar] [CrossRef] [Green Version]
- Melnick, A.; Ahmad, K.F.; Arai, S.; Polinger, A.; Ball, H.; Borden, K.L.; Carlile, G.W.; Prive, G.G.; Licht, J.D. In-depth mutational analysis of the promyelocytic leukemia zinc finger BTB/POZ domain reveals motifs and residues required for biological and transcriptional functions. Mol. Cell. Biol. 2000, 20, 6550–6567. [Google Scholar] [CrossRef] [PubMed]
- Evans, G.E.; Martínez-Conejero, J.A.; Phillipson, G.T.; Sykes, P.H.; Sin, I.L.; Lam, E.Y.; Print, C.G.; Horcajadas, J.A.; Evans, J.J. In the secretory endometria of women, luminal epithelia exhibit gene and protein expressions that differ from those of glandular epithelia. Fertil. Steril. 2014, 102, 307–317. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Liu, J.; Min, Q.; Ikawa, T.; Yasuda, S.; Yang, Y.; Wang, Y.Q.; Tsubata, T.; Zhao, Y.; Wang, J.Y. Kelch like protein 14 promotes B-1a but suppresses B-1b cell development. Int. Immunol. 2018, 30, 311–318. [Google Scholar] [CrossRef] [PubMed]
- Geisert, R.D.; Johnson, G.A.; Burghardt, R.C. Implantation and Establishment of Pregnancy in the Pig. Adv. Anat. Embryol. Cell. Biol. 2015, 216, 137–163. [Google Scholar] [CrossRef]
- Murphy, C.R. Junctional barrier complexes undergo major alterations during the plasma membrane transformation of uterine epithelial cells. Hum. Reprod. 2000, 15, 182–188. [Google Scholar] [CrossRef] [Green Version]
- Murphy, C.R. Uterine receptivity and the plasma membrane transformation. Cell Res. 2004, 14, 259–267. [Google Scholar] [CrossRef]
- Waclawik, A.; Kaczynski, P.; Jabbour, H.N. Autocrine and paracrine mechanisms of prostaglandin E₂ action on trophoblast/conceptus cells through the prostaglandin E₂ receptor (PTGER2) during implantation. Endocrinology 2013, 154, 3864–3876. [Google Scholar] [CrossRef] [Green Version]
- Kubota, K.; Furuse, M.; Sasaki, H.; Sonoda, N.; Fujita, K.; Nagafuchi, A.; Tsukita, S. Ca(2+)-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions. Curr. Biol. 1999, 9, 1035–1038. [Google Scholar] [CrossRef] [Green Version]
- Aplin, J.D.; Ruane, P.T. Embryo-epithelium interactions during implantation at a glance. J. Cell Sci. 2017, 130, 15–22. [Google Scholar] [CrossRef] [Green Version]
- Jalali, B.M.; Lukasik, K.; Witek, K.; Baclawska, A.; Skarzynski, D.J. Changes in the expression and distribution of junction and polarity proteins in the porcine endometrium during early pregnancy period. Theriogenology 2019, 142, 196–206. [Google Scholar] [CrossRef]
- Carraway, K.L.; Price-Schiavi, S.A.; Komatsu, M.; Idris, N.; Perez, A.; Li, P.; Jepson, S.; Zhu, X.; Carvajal, M.E.; Carraway, C.A. Multiple facets of sialomucin complex/MUC4, a membrane mucin and erbb2 ligand, in tumors and tissues (Y2K update). Front. Biosci. 2000, 5, D95–D107. [Google Scholar] [CrossRef] [PubMed]
- Ferrell, A.D.; Malayer, J.R.; Carraway, K.L.; Geisert, R.D. Sialomucin complex (Muc4) expression in porcine endometrium during the oestrous cycle and early pregnancy. Reprod. Domest. Anim. 2003, 38, 63–65. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Kang, S.G.; Kim, J.I.; Park, J.H.; Kim, S.K.; Cho, D.J.; Kim, H. Implication of ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 in implantational remodeling of a mouse uterus. Yonsei Med. J. 2006, 47, 558–567. [Google Scholar] [CrossRef]
- Olson, G.E.; Winfrey, V.P.; Matrisian, P.E.; NagDas, S.K.; Hoffman, L.H. Blastocyst-dependent upregulation of metalloproteinase/disintegrin MDC9 expression in rabbit endometrium. Cell Tissue Res. 1998, 293, 489–498. [Google Scholar] [CrossRef] [PubMed]
- Llamazares, M.; Cal, S.; Quesada, V.; López-Otín, C. Identification and characterization of ADAMTS-20 defines a novel subfamily of metalloproteinases-disintegrins with multiple thrombospondin-1 repeats and a unique GON domain. J. Biol. Chem. 2003, 278, 13382–13389. [Google Scholar] [CrossRef] [Green Version]
- Porter, S.; Clark, I.M.; Kevorkian, L.; Edwards, D.R. The ADAMTS metalloproteinases. Biochem. J. 2005, 386, 15–27. [Google Scholar] [CrossRef] [PubMed]
- Bootcov, M.R.; Bauskin, A.R.; Valenzuela, S.M.; Moore, A.G.; Bansal, M.; He, X.Y.; Zhang, H.P.; Donnellan, M.; Mahler, S.; Pryor, K.; et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. PNAS 1997, 94, 11514–11519. [Google Scholar] [CrossRef] [Green Version]
- Aw Yong, K.M.; Zeng, Y.; Vindivich, D.; Phillip, J.M.; Wu, P.H.; Wirtz, D.; Getzenberg, R.H. Morphological effects on expression of growth differentiation factor 15 (GDF15), a marker of metastasis. J. Cell Physiol. 2014, 229, 362–373. [Google Scholar] [CrossRef] [Green Version]
- Marjono, A.B.; Brown, D.A.; Horton, K.E.; Wallace, E.M.; Breit, S.N.; Manuelpillai, U. Macrophage inhibitory cytokine-1 in gestational tissues and maternal serum in normal and pre-eclamptic pregnancy. Placenta 2003, 24, 100–106. [Google Scholar] [CrossRef]
- Zhao, L.; Isayama, K.; Chen, H.; Yamauchi, N.; Shigeyoshi, Y.; Hashimoto, S.; Hattori, M.A. The nuclear receptor REV-ERBα represses the transcription of growth/differentiation factor 10 and 15 genes in rat endometrium stromal cells. Physiol. Rep. 2016, 4, e12663. [Google Scholar] [CrossRef]
- Morrish, D.W.; Dakour, J.; Li, H. Life and death in the placenta: New peptides and genes regulating human syncytiotrophoblast and extravillous cytotrophoblast lineage formation and renewal. Curr. Protein Pept. Sci. 2001, 2, 245–259. [Google Scholar] [CrossRef] [PubMed]
- Moustakas, A.; Souchelnytskyi, S.; Heldin, C.H. Smad regulation in TGF-beta signal transduction. J. Cell Sci. 2001, 114, 4359–4369. [Google Scholar] [PubMed]
- Burghardt, R.C.; Johnson, G.A.; Jaeger, L.A.; Ka, H.; Garlow, J.E.; Spencer, T.E.; Bazer, F.W. Integrins and extracellular matrix proteins at the maternal–fetal interface in domestic animals. Cells Tissues Organs 2002, 172, 202–217. [Google Scholar] [CrossRef] [PubMed]
- Jaeger, L.A.; Spiegel, A.K.; Ing, N.H.; Johnson, G.A.; Bazer, F.W.; Burghardt, R.C. Functional effects of transforming growth factor beta on adhesive properties of porcine trophectoderm. Endocrinology 2005, 146, 3933–3942. [Google Scholar] [CrossRef] [Green Version]
- Mantena, S.R.; Kannan, A.; Cheon, Y.P.; Li, Q.; Johnson, P.F.; Bagchi, I.C.; Bagchi, M.K. C/EBPbeta is a critical mediator of steroid hormone-regulated cell proliferation and differentiation in the uterine epithelium and stroma. PNAS 2006, 103, 1870–1875. [Google Scholar] [CrossRef] [Green Version]
- Kannan, A.; Fazleabas, A.T.; Bagchi, I.C.; Bagchi, M.K. The transcription factor C/EBPβ is a marker of uterine receptivity and expressed at the implantation site in the primate. Reprod. Sci. 2010, 17, 434–443. [Google Scholar] [CrossRef] [Green Version]
- Tynan, S.; Pacia, E.; Haynes-Johnson, D.; Lawrence, D.; D’Andrea, M.R.; Guo, J.Z.; Lundeen, S.; Allan, G. The putative tumor suppressor deleted in malignant brain tumors 1 is an estrogen-regulated gene in rodent and primate endometrial epithelium. Endocrinology 2005, 146, 1066–1073. [Google Scholar] [CrossRef] [Green Version]
- Kamińska, K.; Wasielak, M.; Bogacka, I.; Blitek, M.; Bogacki, M. Quantitative expression of lysophosphatidic acid receptor 3 gene in porcine endometrium during the periimplantation period and estrous cycle. Prostag. Oth. Lipid M 2008, 85, 26–32. [Google Scholar] [CrossRef]
- Ye, X.; Hama, K.; Contos, J.J.; Anliker, B.; Inoue, A.; Skinner, M.K.; Suzuki, H.; Amano, T.; Kennedy, G.; Arai, H.; et al. LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 2005, 435, 104–108. [Google Scholar] [CrossRef]
- Jeong, W.; Seo, H.; Sung, Y.; Ka, H.; Song, G.; Kim, J. Lysophosphatidic Acid (LPA) Receptor 3-Mediated LPA Signal Transduction Pathways: A Possible Relationship with Early Development of Peri-Implantation Porcine Conceptus. Biol. Reprod. 2016, 94, 104. [Google Scholar] [CrossRef]
- Woclawek-Potocka, I.; Kondraciuk, K.; Skarzynski, D.J. Lysophosphatidic acid stimulates prostaglandin E2 production in cultured stromal endometrial cells through LPA1 receptor. Exp. Biol. Med. 2009, 234, 986–993. [Google Scholar] [CrossRef]
- Ferlita, A.; Battaglia, R.; Andronico, F.; Caruso, S.; Cianci, A.; Purrello, M.; Pietro, C.D. Non-Coding RNAs in Endometrial Physiopathology. Int. J. Mol. Sci. 2018, 19, E2120. [Google Scholar] [CrossRef] [Green Version]
- Filigheddu, N.; Sampietro, S.; Chianale, F.; Porporato, P.E.; Gaggianesi, M.; Gregnanin, I.; Rainero, E.; Ferrara, M.; Perego, B.; Riboni, F.; et al. Diacylglycerol kinase α mediates 17-β-estradiol-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line through the G protein-coupled estrogen receptor GPR30. Cell Signal. 2011, 23, 1988–1996. [Google Scholar] [CrossRef] [PubMed]
- O’Leary, N.A.; Wright, M.W.; Brister, J.R.; Ciufo, S.; Haddad, D.; McVeigh, R.; Rajput, B.; Robbertse, B.; Smith-White, B.; Ako-Adjei, D.; et al. Reference sequence (RefSeq) database at NCBI: Current status, taxonomic expansion and functional annotation. Nucleic Acids Res. 2016, 44, D733–D745. [Google Scholar] [CrossRef] [Green Version]
- Pengchong, H.; Tao, H. Expression of IGF-1R, VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma. Eur. J. Gynaecol. Oncol. 2011, 32, 660–664. [Google Scholar] [PubMed]
- Kaczynski, P.; Kowalewski, M.P.; Waclawik, A. Prostaglandin F2α promotes angiogenesis and embryo-maternal interactions during implantation. Reproduction 2016, 151, 539–552. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huber, W.; von Heydebreck, A.; Sultmann, H.; Poustka, A.; Vingron, M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 2002, 18, S96–S104. [Google Scholar] [CrossRef]
- Smyth, G.K. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 2004, 3. [Google Scholar] [CrossRef]
- Saeed, A.I.; Sharov, V.; White, J.; Li, J.; Liang, W.; Bhagabati, N.; Braisted, J.; Klapa, M.; Currier, T.; Thiagarajan, M.; et al. TM4: A free, open-source system for microarray data management and analysis. Biotechniques 2003, 34, 374–378. [Google Scholar] [CrossRef] [Green Version]
- Bick, J.T.; Zeng, S.; Robinson, M.D.; Ulbrich, S.E.; Bauersachs, S. Mammalian Annotation Database for improved annotation and functional classification of Omics datasets from less well-annotated organisms. Database (Oxford) 2019, baz086. [Google Scholar] [CrossRef]
- Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009, 37, 1–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources. Nature Prot. 2009, 4, 44–57. [Google Scholar] [CrossRef] [PubMed]
- Bardou, P.; Mariette, J.; Escudié, F.; Djemiel, C.; Klopp, C. Jvenn: An interactive Venn diagram viewer. BMC Bioinform. 2014, 15, 293. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaimal, V.; Bardes, E.E.; Tabar, S.C.; Jegga, A.G.; Aronow, B.J. ToppCluster: A multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems. Nucleic Acids Res. 2010, 38, W96–W102. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krämer, A.; Green, J.; Pollard, J., Jr.; Tugendreich, S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics 2014, 30, 523–530. [Google Scholar] [CrossRef] [PubMed]
- Zhao, S.; Fernald, R.D. Comprehensive algorithm for quantitative real-time polymerase chain reaction. J. Comput. Biol. 2005, 12, 1047–1064. [Google Scholar] [CrossRef] [PubMed]
- Andersen, C.L.; Jensen, J.L.; Ørntoft, T.F. Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 2004, 64, 5245–5250. [Google Scholar] [CrossRef] [Green Version]
Selected Functional Terms of Overrepresented Annotation Clusters | Enrichment Score |
---|---|
E2 – 833 ng/infusion | |
UP REGULATED | |
extracellular exosome (45; 1.85), extracellular vesicle (45; 1.84) | 3.76 |
glucose metabolic process (8; 5.41) | 2.60 |
calcium ion transport (9; 3.14), ion homeostasis (16; 2.95), transmembrane transport (21; 2.05) | 2.31 |
protein phosphorylation (28; 1.95) | 2.07 |
positive regulation of cell growth (6; 5.02) | 1.89 |
epithelial cell differentiation (12; 2.75) | 1.79 |
cell adhesion (23; 1.74) | 1.72 |
response to hypoxia (6; 2.71) | 1.51 |
regulation of cell migration (11; 2.07) | 1.45 |
placenta development (5; 4.45) | 1.43 |
regulation of blood circulation (7; 3.01) | 1.42 |
DOWN REGULATED | |
extracellular exosome (23; 1.65), extracellular vesicle (23; 1.64) | 1.78 |
steroid metabolic process (5; 3.59), lipid metabolism (6; 2.88) | 1.66 |
protein ubiquitination (12; 3.09) | 1.65 |
calcium transport (3; 6.36), sodium ion transport (5, 4.98), active transmembrane transporter activity (7, 3.60) | 1.59 |
E2 – 33.3 μg/infusion | |
UP REGULATED | |
extracellular exosome (338; 1.85) extracellular vesicle (339; 1.85) | 30.04 |
focal adhesion (77; 3.03), cell junction (143; 1.60) | 13.69 |
regulation of inflammatory response (56; 2.96) | 12.95 |
cell migration (135; 1.89) | 9.57 |
cell proliferation (177; 1.58) | 8.04 |
apoptotic process (177; 1.62) | 7.67 |
positive regulation of mapk cascade (58; 2.02), activation of mapk activity (21; 2.39) | 7.62 |
angiogenesis (61; 2.45) | 7.32 |
cytokine production (75; 1.98) | 6.77 |
leukocyte migration (59; 2.61) | 5.70 |
lipid metabolism (57; 2.09) | 4.72 |
gland development (54; 2.13) | 4.37 |
response to hypoxia (38; 2.21) | 3.77 |
cell division (64; 1.84), mitotic cell cycle (96; 1.64), regulation of cell cycle (81; 1.38) | 3.54 |
maternal process involved in female pregnancy (11; 3.10), female pregnancy (28; 2.49); multi-organism reproductive process (70; 1.24) | 3.37 |
ecm-receptor interaction (20; 2.79), extracellular matrix component (19; 2.28), extracellular matrix (27; 2.01) | 3.12 |
protein transport (153; 1.37), intracellular protein transport (78; 1.28) | 3.09 |
protein processing (37; 2.61), protein maturation (40; 2.45) | 3.03 |
cellular response to interferon-gamma (20; 2.46) | 3.02 |
epithelial cell proliferation (39; 1.87) | 2.57 |
endothelium development (19; 2.84), endothelial cell differentiation (14; 2.45) | 2.54 |
steroid hormone receptor binding (15; 3.10), hormone receptor binding (21; 2.29), nuclear hormone receptor binding (18; 2.28) | 2.13 |
DOWN REGULATED | |
cell development (111; 1.31), regulation of cell differentiation (88; 1.33) | 4.06 |
cytoskeletal protein binding (59; 1.59) | 2.84 |
cell migration (67; 1.32) | 2.32 |
histone acetylation (16; 2.57) | 2.05 |
import into cell (10; 3.28) | 1.74 |
negative chemotaxis (8; 4.54) | 1.67 |
Day 12 of pregnancy vs day 12 of the estrous cycle | |
UPREGULATED | |
vasculature development (54; 3.12) | 11.26 |
cell migration (76; 2.26) | 9.78 |
extracellular exosome (464; 1.51), extracellular vesicle (464; 1.50) | 6.67 |
mitotic cell cycle (57; 2.02), cell cycle process (64; 1.66) | 5.65 |
regulation of signal transduction (116; 1.50) | 5.32 |
focal adhesion (32; 2.56 ), adherens junction (42; 1.89) | 4.81 |
regulation of protein phosphorylation (67; 1.81) | 4.75 |
tissue migration (22; 3.27), epithelial cell migration (19; 2.93) | 4.55 |
response to hypoxia (22; 2.71) | 4.04 |
activation of innate immune response (18; 2.53) | 3.28 |
endothelial cell development (9; 5.37), endothelium development (11; 3.49) | 3.12 |
immune response-regulating signaling pathway (28; 1.86) | 2.26 |
immune system development (39; 1.67) | 2.08 |
in utero embryonic development (20; 2.13) | 1.84 |
DOWN REGULATED | |
oxidation-reduction process (25; 2.31), organic acid metabolic process (21; 2.11), fatty acid metabolic process (11; 2.73), lipid metabolism (11; 2.63), lipid biosynthesis (5, 3.31) fatty acid biosynthesis (3; 5.97) | 2.13 |
regulation of extent of cell growth (7; 6.12) | 1.95 |
regulation of cell morphogenesis (16; 2.56), regulation of cell differentiation (30; 1.77), regulation of anatomical structure size (13; 2.44) | 1.92 |
response to calcium ion (6; 4.63) | 1.89 |
circulatory system development (19; 1.83) | 1.62 |
response to hormone (16; 1.70) | 1.60 |
regulation of transport (29; 1.47) | 1.36 |
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Kaczynski, P.; Bauersachs, S.; Baryla, M.; Goryszewska, E.; Muszak, J.; Grzegorzewski, W.J.; Waclawik, A. Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo. Int. J. Mol. Sci. 2020, 21, 890. https://doi.org/10.3390/ijms21030890
Kaczynski P, Bauersachs S, Baryla M, Goryszewska E, Muszak J, Grzegorzewski WJ, Waclawik A. Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo. International Journal of Molecular Sciences. 2020; 21(3):890. https://doi.org/10.3390/ijms21030890
Chicago/Turabian StyleKaczynski, Piotr, Stefan Bauersachs, Monika Baryla, Ewelina Goryszewska, Jolanta Muszak, Waldemar J. Grzegorzewski, and Agnieszka Waclawik. 2020. "Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo" International Journal of Molecular Sciences 21, no. 3: 890. https://doi.org/10.3390/ijms21030890