Endometrial gene expression profiling in pregnant Meishan and Yorkshire pigs on day 12 of gestation

Differentially expressed genes; Endometrium; Implantation; Pig; Prolificacy; Meishan pig; Yorkshire pig; Suidae; Sus; Animals; Cluster Analysis; Computational Biology; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Litter Size; Molecular Sequence Annotation; Pregnancy; Reproducibility of Results; Swine; Transcriptome

Abstract :

[en] Background: Litter size in pigs is a major factor affecting the profitability in the pig industry. The peri-implantation window in pigs is characterized by the coordinated interactions between the maternal uterine endometrium and the rapidly elongating conceptuses and represents a period of time during which a large percentage of the developing conceptuses are lost. However, the gene expression and regulatory networks in the endometrium contributing to the establishment of the maternal: placental interface remain poorly understood.Results: We characterized the endometrial gene expression profile during the peri-implantation stage of development by comparing two breeds that demonstrate very different reproductive efficiencies. We employed the porcine Affymetrix GeneChip® to assay the transcriptomic profiles of genes expressed in the uterine endometrium obtained from Meishan and Yorkshire gilts (n = 4 for each breed) on day 12 of gestation (M12 and Y12, respectively). Total of 17,076 probesets were identified as "present" in at least two arrays. A mixed model-based statistical analysis predicted a total of 2,656 (q < 0.1) transcripts as differentially expressed between Meishan and Yorkshire pigs. Eighteen differentially expressed transcripts of interest were validated by quantitative real-time PCR. Gene ontology (GO) annotation revealed that the known functions of the differentially expressed genes were involved in a series of important biological processes relevant to early pregnancy establishment in the pig.Conclusions: The results identified endometrial gene expression profiles of two breeds differing in litter size and identified candidate genes that are related to known physiological pathways related to reproductive prolificacy. These findings provide a deeper understanding of molecular pathways differing between two breeds at the critical peri-implantation stage of pregnancy, which can be utilized to better understand the events contributing to pregnancy establishment in the pig. © 2014 Gu et al.; licensee BioMed Central Ltd.

Disciplines :

Animal production & animal husbandry

Author, co-author :

Gu, T.; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China

Zhu, M.-J.; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China

Schroyen, Martine ; Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Zootechnie

Qu, L.; Department of Statistics, Iowa State University, Ames 50011, United States

Nettleton, D.; Department of Statistics, Iowa State University, Ames 50011, United States

Kuhar, D.; Animal Parasitic Diseases Laboratory, BARC, ARS, USDA, Beltsville, MD 20705, United States

Lunney, J. K.; Animal Parasitic Diseases Laboratory, BARC, ARS, USDA, Beltsville, MD 20705, United States

Ross, J. W.; Department of Animal Science, Iowa State University, Ames 50011, United States

Zhao, S.-H.; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China, Department of Animal Science, Iowa State University, Ames 50011, United States

Tuggle, C. K.; Department of Animal Science, Iowa State University, Ames 50011, United States

Title :

Endometrial gene expression profiling in pregnant Meishan and Yorkshire pigs on day 12 of gestation

Publication date :

2014

Journal title :

BMC Genomics

eISSN :

1471-2164

Publisher :

BioMed Central

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

NRI 2004-35205-14202, USDA, U.S. Department of Agriculture

Available on ORBi :

since 24 April 2017

Statistics

Number of views

56 (2 by ULiège)

Number of downloads

107 (1 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Spencer TE, Bazer FW. Uterine and placental factors regulating conceptus growth in domestic animals. J Anim Sci 2004, 82 E-Suppl:E4-13.
Lunney JK. Advances in swine biomedical model genomics. Int J Biol Sci 2007, 3(3):179-184. 1802015, 17384736.
Ross JW, de Castro JP F, Zhao J, Samuel M, Walters E, Rios C, Bray-Ward P, Jones BW, Marc RE, Wang W, et al. Generation of an inbred miniature pig model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 2012, 53(1):501-507. 10.1167/iovs.11-8784, 3292381, 22247487.
Yang CX, Ross JW. Genetic Modification of Domestic Animals for Agriculture and Biomedical Applications. Biomedical Science, Engineering and Technology 2012, 697-726. Rijeka, Croatia: InTech Publishing, Ghista DN.
Spotter A, Distl O. Genetic approaches to the improvement of fertility traits in the pig. Vet J 2006, 172(2):234-247. 10.1016/j.tvjl.2005.11.013, 16426876.
Legault C, Gruand J. Amélioration de la prolificité des truies par la création d'une lignée "hyperprolifique" et l'usage de l'insemination artificielle: principe et résultats experimentaux préliminaires. J Rech Porcine Fr 1976, 8:201-206.
Rothschild M, Bidanel J. Biology and genetics of reproduction. The Genetics of the pig 1998, 313-343. Cambridge, UK: CAB international, University Press, Rothschild MF, Ruvinsky A.
Rothschild M, Jacobson C, Vaske D, Tuggle C, Wang L, Short T, Eckardt G, Sasaki S, Vincent A, McLaren D, et al. The estrogen receptor locus is associated with a major gene influencing litter size in pigs. Proc Natl Acad Sci USA 1996, 93(1):201-205. 10.1073/pnas.93.1.201, 40206, 8552604.
Pope WF. Embryonic mortality in swine. Embryonic Mortality in Domestic Species 1994, 53-77. Boca Raton: CRC press, Zavy MT, Geisert RD.
Yelich JV, Pomp D, Geisert RD. Detection of transcripts for retinoic acid receptors, retinol-binding protein, and transforming growth factors during rapid trophoblastic elongation in the porcine conceptus. Biol Reprod 1997, 57(2):286-294. 10.1095/biolreprod57.2.286, 9241041.
Ross JW, Ashworth MD, Stein DR, Couture OP, Tuggle CK, Geisert RD. Identification of differential gene expression during porcine conceptus rapid trophoblastic elongation and attachment to uterine luminal epithelium. Physiol Genomics 2009, 36(3):140-148.
Geisert RD, Ross JW, Ashworth MD, White FJ, Johnson GA, DeSilva U. Maternal recognition of pregnancy signal or endocrine disruptor: the two faces of oestrogen during establishment of pregnancy in the pig. Soc Reprod Fertil Suppl 2006, 62:131-145.
Ashworth MD, Ross JW, Stein DR, Allen DT, Spicer LJ, Geisert RD. Endocrine disruption of uterine insulin-like growth factor expression in the pregnant gilt. Reproduction 2005, 130(4):545-551. 10.1530/rep.1.00821, 16183872.
Joyce MM, Burghardt RC, Geisert RD, Burghardt JR, Hooper RN, Ross JW, Ashworth MD, Johnson GA. Pig conceptuses secrete estrogen and interferons to differentially regulate uterine STAT1 in a temporal and cell type-specific manner. Endocrinol 2007, 148(9):4420-4431.
Ross JW, Ashworth MD, White FJ, Johnson GA, Ayoubi PJ, DeSilva U, Whitworth KM, Prather RS, Geisert RD. Premature estrogen exposure alters endometrial gene expression to disrupt pregnancy in the pig. Endocrinol 2007, 148(10):4761-4773.
Vallee M, Beaudry D, Roberge C, Matte JJ, Blouin R, Palin MF. Isolation of differentially expressed genes in conceptuses and endometrial tissue of sows in early gestation. Biol Reprod 2003, 69(5):1697-1706. 10.1095/biolreprod.103.019307, 12890725.
Tayade C, Black GP, Fang Y, Croy BA. Differential gene expression in endometrium, endometrial lymphocytes, and trophoblasts during successful and abortive embryo implantation. J Immunol 2006, 176(1):148-156.
Wessels JM, Linton NF, Croy BA, Tayade C. A review of molecular contrasts between arresting and viable porcine attachment sites. Am J Reprod Immunol 2007, 58(6):470-480. 10.1111/j.1600-0897.2007.00534.x, 17997745.
Fu Y, Fu J, Wang A. Association of EphA4 polymorphism with swine reproductive traits and mRNA expression of EphA4 during embryo implantation. Mol Biol Rep 2012, 39(3):2689-2696. 10.1007/s11033-011-1023-8, 21688153.
Wu YP, Wang AG, Li N, Fu JL, Zhao XB. Association with TGF-beta1 gene polymorphisms and reproductive performance of large white pig. Reprod Domest Anim 2010, 45(6):1028-1032. 10.1111/j.1439-0531.2009.01480.x, 20088852.
Lee SH, Zhao SH, Recknor JC, Nettleton D, Orley S, Kang SK, Lee BC, Hwang WS, Tuggle CK. Transcriptional profiling using a novel cDNA array identifies differential gene expression during porcine embryo elongation. Mol Reprod Dev 2005, 71(2):129-139. 10.1002/mrd.20291, 15791594.
Tuggle CK, Green JA, Fitzsimmons C, Woods R, Prather RS, Malchenko S, Soares BM, Kucaba T, Crouch K, Smith C, et al. EST-based gene discovery in pig: virtual expression patterns and comparative mapping to human. Mamm Genome 2003, 14(8):565-579. 10.1007/s00335-002-2263-7, 12925889.
Ross JW, Ashworth MD, Hurst AG, Malayer JR, Geisert RD. Analysis and characterization of differential gene expression during rapid trophoblastic elongation in the pig using suppression subtractive hybridization. Reprod Biol Endocrinol 2003, 1:23. 10.1186/1477-7827-1-23, 151795, 12646053.
Ross JW, Malayer JR, Ritchey JW, Geisert RD. Characterization of the interleukin-1beta system during porcine trophoblastic elongation and early placental attachment. Biol Reprod 2003, 69(4):1251-1259. 10.1095/biolreprod.103.015842, 12801990.
Ostrup E, Bauersachs S, Blum H, Wolf E, Hyttel P. Differential endometrial gene expression in pregnant and nonpregnant sows. Biol Reprod 2010, 83(2):277-285. 10.1095/biolreprod.109.082321, 20393170.
le Blomberg A, Schreier L, Li RW. Characteristics of peri-implantation porcine concepti population and maternal milieu influence the transcriptome profile. Mol Reprod Dev 2010, 77(11):978-989. 10.1002/mrd.21253, 21104768.
Zhou QY, Fang MD, Huang TH, Li CC, Yu M, Zhao SH. Detection of differentially expressed genes between Erhualian and large white placentas on day 75 and 90 of gestation. BMC Genomics 2009, 10:337. 10.1186/1471-2164-10-337, 2724418, 19630995.
Ford SP. Embryonic and fetal development in different genotypes in pigs. J Reprod Fertil Suppl 1997, 52:165-176.
Haley CS, Lee GJ. Genetic basis of prolificacy in Meishan pigs. J Reprod Fertil Suppl 1993, 48:247-259.
Haley CS, Lee GJ, Ritchie M. Comparative reproductive performance in Meishan and large white pigs and their crosses. Anim Sci 1995, 60:259-267.
Biensen NJ, Wilson ME, Ford SP. The impact of either a Meishan or Yorkshire uterus on Meishan or Yorkshire fetal and placental development to days 70, 90, and 110 of gestation. J Anim Sci 1998, 76(8):2169-2176.
Stinckens A, Mathur P, Janssens S, Bruggeman V, Onagbesan OM, Schroyen M, Spincemaille G, Decuypere E, Georges M, Buys N. Indirect effect of IGF2 intron3 g.3072G>A mutation on prolificacy in sows. Anim Genet 2010, 41(5):493-498. 10.1111/j.1365-2052.2010.02040.x, 20394605.
Youngs CR, Ford SP, McGinnis LK, Anderson LH. Investigations into the control of litter size in swine: I. Comparative studies on in vitro development of Meishan and Yorkshire preimplantation embryos. J Anim Sci 1993, 71(6):1561-1565.
Wilson ME, Ford SP. Differences in trophectoderm mitotic rate and P450 17alpha-hydroxylase expression between late preimplantation Meishan and Yorkshire conceptuses. Biol Reprod 1997, 56(2):380-385. 10.1095/biolreprod56.2.380, 9116136.
Bazer FW, Thatcher WW, Martinat-Botte F, Terqui M. Conceptus development in large white and prolific Chinese Meishan pigs. J Reprod Fertil 1988, 84(1):37-42. 10.1530/jrf.0.0840037, 3184056.
Biensen NJ, Wilson ME, Ford SP. The impacts of uterine environment and fetal genotype on conceptus size and placental vascularity during late gestation in pigs. J Anim Sci 1999, 77(4):954-959.
Fernandez-Rodriguez A, Munoz M, Fernandez A, Pena RN, Tomas A, Noguera JL, Ovilo C, Fernandez AI. Differential gene expression in ovaries of pregnant pigs with high and low prolificacy levels and identification of candidate genes for litter size. Biol Reprod 2011, 84(2):299-307. 10.1095/biolreprod.110.085589, 20926806.
Lockhart DJ, Dong H, Byrne MC, Follettie MT, Gallo MV, Chee MS, Mittmann M, Wang C, Kobayashi M, Horton H, et al. Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat Biotechnol 1996, 14(13):1675-1680. 10.1038/nbt1296-1675, 9634850.
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003, 34(3):267-273. 10.1038/ng1180, 12808457.
Zhao SH, Recknor J, Lunney JK, Nettleton D, Kuhar D, Orley S, Tuggle CK. Validation of a first-generation long-oligonucleotide microarray for transcriptional profiling in the pig. Genomics 2005, 86(5):618-625. 10.1016/j.ygeno.2005.08.001, 16216716.
Couture O, Callenberg K, Koul N, Pandit S, Younes R, Hu ZL, Dekkers J, Reecy J, Honavar V, Tuggle C. ANEXdb: an integrated animal ANnotation and microarray EXpression database. Mamm Genome 2009, 20(11-12):768-777.
Tuggle CK, Wang Y, Couture O. Advances in swine transcriptomics. Int J Biol Sci 2007, 3(3):132-152. 1802012, 17384733.
Pierzynski P, Reinheimer TM, Kuczynski W. Oxytocin antagonists may improve infertility treatment. Fertil Steril 2007, 88(1):213. e219-222.
Moraloglu O, Tonguc E, Var T, Zeyrek T, Batioglu S. Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF. Reprod Biomed Online 2010, 21(3):338-343. 10.1016/j.rbmo.2010.04.009, 20638340.
Ashworth MD, Ross JW, Hu J, White FJ, Stein DR, Desilva U, Johnson GA, Spencer TE, Geisert RD. Expression of porcine endometrial prostaglandin synthase during the estrous cycle and early pregnancy, and following endocrine disruption of pregnancy. Biol Reprod 2006, 74(6):1007-1015. 10.1095/biolreprod.105.046557, 16452463.
Zhang H, Wang S, Liu M, Zhang A, Wu Z, Zhang Z, Li J. Differential gene expression in the endometrium on gestation day 12 provides insight into sow prolificacy. BMC Genomics 2013, 14:45. 10.1186/1471-2164-14-45, 3610143, 23339594.
Wu D, Song D, Li X, Yu M, Li C, Zhao S. Molecular characterization and identification of the E2/P4 response element in the porcine HOXA10 gene. Mol Cell Biochem 2013, 374(1-2):213-222.
Blitek A, Morawska E, Kiewisz J, Ziecik AJ. Effect of conceptus secretions on HOXA10 and PTGS2 gene expression, and PGE2 release in co-cultured luminal epithelial and stromal cells of the porcine endometrium at the time of early implantation. Theriogenology 2011, 76(5):954-966. 10.1016/j.theriogenology.2011.05.002, 21705055.
Kyo S, Sakaguchi J, Kiyono T, Shimizu Y, Maida Y, Mizumoto Y, Mori N, Nakamura M, Takakura M, Miyake K, et al. Forkhead transcription factor FOXO1 is a direct target of progestin to inhibit endometrial epithelial cell growth. Clin Cancer Res 2011, 17(3):525-537. 10.1158/1078-0432.CCR-10-1287, 21131554.
Wilson ME, Ford SP. Effect of estradiol-17beta administration during the time of conceptus elongation on placental size at term in Meishan pigs. J Anim Sci 2000, 78(4):1047-1052.
Vestweber D. VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Arterioscler Thromb Vasc Biol 2008, 28(2):223-232.
Tapia A, Gangi LM, Zegers-Hochschild F, Balmaceda J, Pommer R, Trejo L, Pacheco IM, Salvatierra AM, Henriquez S, Quezada M, et al. Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy. Hum Reprod 2008, 23(2):340-351.
Massuto DA, Kneese EC, Johnson GA, Burghardt RC, Hooper RN, Ing NH, Jaeger LA. Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus-maternal interface. Reproduction 2010, 139(2):465-478. 10.1530/REP-09-0447, 19920116.
Oku N, Sasabe E, Ueta E, Yamamoto T, Osaki T. Tight junction protein claudin-1 enhances the invasive activity of oral squamous cell carcinoma cells by promoting cleavage of laminin-5 gamma2 chain via matrix metalloproteinase (MMP)-2 and membrane-type MMP-1. Cancer Res 2006, 66(10):5251-5257. 10.1158/0008-5472.CAN-05-4478, 16707450.
Riesewijk A, Martin J, van Os R, Horcajadas JA, Polman J, Pellicer A, Mosselman S, Simon C. Gene expression profiling of human endometrial receptivity on days LH + 2 versus LH + 7 by microarray technology. Mol Hum Reprod 2003, 9(5):253-264. 10.1093/molehr/gag037, 12728018.
Raghupathy R. Pregnancy: success and failure within the Th1/Th2/Th3 paradigm. Semin Immunol 2001, 13(4):219-227. 10.1006/smim.2001.0316, 11437629.
Makhseed M, Raghupathy R, Azizieh F, Omu A, Al-Shamali E, Ashkanani L. Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions. Hum Reprod 2001, 16(10):2219-2226. 10.1093/humrep/16.10.2219, 11574519.
Granot I, Gnainsky Y, Dekel N. Endometrial inflammation and effect on implantation improvement and pregnancy outcome. Reproduction 2012, 144(6):661-668. 10.1530/REP-12-0217, 23028125.
Jin LP, Fan DX, Zhang T, Guo PF, Li DJ. The costimulatory signal upregulation is associated with Th1 bias at the maternal-fetal interface in human miscarriage. Am J Reprod Immunol 2011, 66(4):270-278. 10.1111/j.1600-0897.2011.00997.x, 21481059.
Zhou WH, Dong L, Du MR, Zhu XY, Li DJ. Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: involvement of CD80/86 and CD28/CTLA-4. Reproduction 2008, 135(3):385-395. 10.1530/REP-07-0063, 18299432.
Du MR, Dong L, Zhou WH, Yan FT, Li DJ. Cyclosporin a improves pregnancy outcome by promoting functions of trophoblasts and inducing maternal tolerance to the allogeneic fetus in abortion-prone matings in the mouse. Biol Reprod 2007, 76(5):906-914. 10.1095/biolreprod.106.056648, 17229932.
Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T. Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol 2000, 165(5):2637-2642.
Tayade C, Esadeg S, Fang Y, Croy BA. Functions of alpha 2 macroglobulins in pregnancy. Mol Cell Endocrinol 2005, 245(1-2):60-66.
Sass-Kuhn SP, Moqbel R, Mackay JA, Cromwell O, Kay AB. Human granulocyte/pollen-binding protein. Recognition and identification as transferrin. J Clin Invest 1984, 73(1):202-210. 10.1172/JCI111192, 424998, 6690479.
Chae JI, Kim J, Lee SG, Jeon YJ, Kim DW, Soh Y, Seo KS, Lee HK, Choi NJ, Ryu J, et al. Proteomic analysis of pregnancy-related proteins from pig uterus endometrium during pregnancy. Proteome Sci 2011, 9:41. 10.1186/1477-5956-9-41, 3162492, 21791079.
Jetten AM. Recent advances in the mechanisms of action and physiological functions of the retinoid-related orphan receptors (RORs). Curr Drug Targets Inflamm Allergy 2004, 3(4):395-412. 10.2174/1568010042634497, 15584888.
Zenri F, Hiroi H, Momoeda M, Tsutsumi R, Hosokawa Y, Koizumi M, Nakae H, Osuga Y, Yano T, Taketani Y. Expression of retinoic acid-related orphan receptor alpha and its responsive genes in human endometrium regulated by cholesterol sulfate. J Steroid Biochem Mol Biol 2012, 128(1-2):21-28.
Laursen KB, Mongan NP, Zhuang Y, Ng MM, Benoit YD, Gudas LJ. Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene. Nucleic Acids Res 2013, 41(13):6430-6443. 10.1093/nar/gkt367, 3905905, 23666625.
Kim EJ, Yoo YG, Yang WK, Lim YS, Na TY, Lee IK, Lee MO. Transcriptional activation of HIF-1 by RORalpha and its role in hypoxia signaling. Arterioscler Thromb Vasc Biol 2008, 28(10):1796-1802. 10.1161/ATVBAHA.108.171546, 18658046.
Koos RD, Kazi AA, Roberson MS, Jones JM. New insight into the transcriptional regulation of vascular endothelial growth factor expression in the endometrium by estrogen and relaxin. Ann N Y Acad Sci 2005, 1041:233-247. 10.1196/annals.1282.037, 15956714.
Dos Santos E, Serazin V, Morvan C, Torre A, Wainer R, de Mazancourt P, Dieudonne MN. Adiponectin and leptin systems in human endometrium during window of implantation. Fertil Steril 2012, 97(3):771-778. e771, 10.1016/j.fertnstert.2011.12.042, 22265003.
Tanaka K, Minoura H, Isobe T, Yonaha H, Kawato H, Wang DF, Yoshida T, Kojima M, Kangawa K, Toyoda N. Ghrelin is involved in the decidualization of human endometrial stromal cells. J Clin Endocrinol Metab 2003, 88(5):2335-2340. 10.1210/jc.2002-021024, 12727993.
Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci USA 2003, 100(16):9440-9445. 10.1073/pnas.1530509100, 170937, 12883005.
Dawson K, Rodriguez RL, Malyj W. Sample phenotype clusters in high-density oligonucleotide microarray data sets are revealed using Isomap, a nonlinear algorithm. BMC Bioinformatics 2005, 6:195. 10.1186/1471-2105-6-195, 1189082, 16076401.