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Placental Up-Regulation of Leptin and ARMS2 is Associated with Growth Discordance in Monochorionic Diamniotic Twin Pregnancies

  • Luming Sun (a1) (a2) (a3), Jia Zhou (a1), Kai Wang (a1), Jian Wang (a2) (a3), Ling Shang (a4), Jianguang Zhang (a4), Junqing Wu (a2) (a3) and David S. Cram (a4) (a5)...

Abstract

Fetal growth discordance is a relatively common complication of monochorionic diamniotic (MCDA) twin pregnancies and is caused by a combination of maternal and placental factors. The aim of the study was to survey placental gene expression patterns and identify genes associated with growth discordance. Clinical samples comprised eight growth-discordant MCDA twin placentas (31+3–34+4 weeks gestational age) and six growth-concordant twin placentas (31+2–37 weeks gestational age). Gene expression libraries were constructed from placental biopsy samples and analyzed by RNA-sequencing. The distribution and relative abundance of mRNA transcripts expressed in the smaller and larger placentas from growth-discordant and concordant MCDA twins was remarkably similar. However, leptin (LEP) and age-related maculopathy susceptibility 2 (ARMS2) mRNA levels were exclusively up-regulated in all of the eight smaller growth-discordant twin placentas. Quantitative real-time PCR of independent biopsy samples confirmed the levels of differential mRNA expression for both genes. Immunohistochemical analysis of tissue sections from matching twin placentas showed increased leptin expression in 5–10% of blood vessel cells of the smaller placenta and marginally higher levels of ARMS2 expression in the microvillous membrane of the smaller placenta. Based on these findings, we speculate that up-regulation of leptin and ARMS2 forms part of an important survival mechanism to compensate for placental growth discordance. Since, leptin and ARMS2 are both expressed as soluble proteins, they may have clinical potential as measurable biomarkers for predicting the onset of growth discordance in MCDA twin pregnancies.

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Copyright

Corresponding author

address for correspondence: David S. Cram, Berry Genomics Corporation, Building 9, No 6 Court Jingshun East Road, Chaoyang District, Beijing, 100015, China. E-mail: david.cram@berrygenomics.com; Luming Sun, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, Gaoke West Road, Pudong New Area, Shanghai, 201204, China. E-mail: luming_sun@163.com

References

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Acosta-Rojas, R., Becker, J., Munoz-Abellana, B., Ruiz, C., Carreras, E., Gratacos, E., & Catalunya and Balears Monochorionic Network. (2007). Twin chorionicity and the risk of adverse perinatal outcome. International Journal of Gynaecology and Obstetrics, 96, 98102.
Allison, M. B., & Myers, M. G. Jr. (2014). 20 years of leptin: Connecting leptin signaling to biological function. Journal of Endocrinology, 223, T25–T35.
Bejar, R., Vigliocco, G., Gramajo, H., Solana, C., Benirschke, K., & Resnik, R. (1990). Antenatal origin of neurologic damage in newborn infants. II. Multiple gestations. American Journal of Obstetrics and Gynecology, 162, 12301236.
Bell, J. T., & Saffery, R. (2012). The value of twins in epigenetic epidemiology. International Journal of Epidemiology, 41, 140150.
Chang, Y. L., Chang, S. D., Chao, A. S., Hsieh, P. C., Wang, C. N., & Wang, T. H. (2009). Clinical outcome and placental territory ratio of monochorionic twin pregnancies and selective intrauterine growth restriction with different types of umbilical artery doppler. Prenatal Diagnosis, 29, 253256.
Cosmi, E., Visentin, S., Favretto, D., Tucci, M., Ragazzi, E., Viel, G., & Ferrara, S. D. (2013). Selective intrauterine growth restriction in monochorionic twin pregnancies: Markers of endothelial damage and metabolomic profile. Twin Research and Human Genetics, 16, 816826.
Fritsche, L. G., Loenhardt, T., Janssen, A., Fisher, S. A., Rivera, A., Keilhauer, C. N., & Weber, B. H. (2008). Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nature Genetics, 40, 892896.
Gao, Y., He, Z., Wang, Z., Luo, Y., Sun, H., Zhou, Y., . . . Jiang, S. (2012). Increased expression and altered methylation of HERVWE1 in the human placentas of smaller fetuses from monozygotic, dichorionic, discordant twins. PLoS One, 7, e33503.
Gordon, L., Joo, J. H., Andronikos, R., Ollikainen, M., Wallace, E. M., Umstad, M. P., . . . Craig, J. M. (2011). Expression discordance of monozygotic twins at birth: Effect of intrauterine environment and a possible mechanism for fetal programming. Epigenetics, 6, 579592.
Gratacós, E., Lewi, L., Muñoz, B., Acosta-Rojas, R., Hernandez-Andrade, E., Martinez, J. M., . . . Deprest, J. (2007). A classification system for intrauterine growth restriction in monochorionic pregnancies according to umbilical artery doppler flow in the smaller twin. Ultrasound in Obstetrics & Gynecology, 30, 2834.
Hack, K. E., Nikkels, P. G., Koopman-Esseboom, C., Derks, J. B., Elias, S. G., van, Gemert, M. J., & Visser, G. H. (2008). Placental characteristics of monochorionic diamniotic twin pregnancies in relation to perinatal outcome. Placenta, 29, 976981.
Horie-Inoue, K., & Inoue, S. (2014). Genomic aspects of age-related macular degeneration. Biochemical and Biophysical Research Communications, 452, 263275.
Huang, X., Yuan, T., Tschannen, M., Sun, Z., Jacob, H., Du, M., . . . Wang, L. (2013). Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics, 14, 319.
Kaminsky, Z. A., Tang, T., Wang, S. C., Ptak, C., Oh, G. H., Wong, A. H., . . . Petronis, A. (2009). DNA methylation profiles in monozygotic and dizygotic twins. Nature Genetics, 41, 240245.
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013). TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biology, 14, R36.
Kim, J., Zhao, K., Jiang, P., Lu, Z. X., Wang, J., Murray, J. C., & Xing, Y. (2012). Transcriptome landscape of the human placenta. BMC Genomics, 13, 115.
Koh, W., Pan, W., Gawad, C., Fan, H. C., Kerchner, G. A., Wyss-Coray, T., . . . Quake, S. R. (2014). Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. Proceedings of the National Academy of Sciences of the United States of America, 111, 73617366.
Kortvely, E., Hauck, S. M., Duetsch, G., Gloeckner, C. J., Kremmer, E., Alge-Priglinger, C. S., . . . Ueffing, M. (2010). ARMS2 is a constituent of the extracellular matrix providing a link between familial and sporadic age-related macular degenerations. Investigative Ophthalmology & Visual Science, 51, 7988.
Lewi, L., Cannie, M., Blickstein, I., Jani, J., Huber, A., Hecher, K., . . . Deprest, J. (2007). Placental sharing, birthweight discordance, and vascular anastomoses in monochorionic diamniotic twin placentas. American Journal of Obstetrics and Gynecology, 197, 587e1587e8.
Lewi, L., Devlieger, R., De Catte, , L., & Deprest, J. (2014). Growth discordance. Best Practice Research Clinical Obstetrics & Gynaecology, 28, 295303.
Li, M. C., Fang, Q., He, Z. M., Gao, Y., & Zhou, Y. (2013). Placental expression of osteopontin(OPN) in monochorionic twins with discordant growth. Placenta, 34, 288290.
Liang, D., Lv, W., Wang, H., Xu, L., Liu, J., Li, H., . . . Wu, L. (2013). Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing. Prenatal Diagnosis, 33, 409415.
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., . . . Ranganathan, S. (1995). Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine, 1, 11551161.
Marr, A. K., Boughorbel, S., Presnell, S., Quinn, C., Chaussabel, D., & Kino, T. (2016). A curated transcriptome dataset collection to investigate the development and differentiation of the human placenta and its associated pathologies. F1000Research, 5, 305.
McCarthy, C., Cotter, F. E., McElwaine, S., Twomey, A., Mooney, E. E., Ryan, F., & Vaughan, J. (2007). Altered gene expression patterns in intrauterine growth restriction: Potential role of hypoxia. American Journal of Obstetrics and Gynecology, 196, 70.e170.e6.
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008). Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods, 5, 621628.
Nishizawa, H., Ota, S., Suzuki, M., Kato, T., Sekiya, T., Kurahashi, H., & Udagawa, Y. (2011). Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction. Reproductive Biology and Endocrinology, 9, 107.
Pérez-Pérez, A., Sánchez-Jiménez, F., Maymó, J., Dueñas, J. L., Varone, C., & Sánchez-Margalet, V. (2015). Role of leptin in female reproduction. Clinical Chemistry and Laboratory Medicine, 53, 1528.
Ratnapriya, R., & Chew, E. Y. (2013). Age-related macular degeneration – clinical review and genetics update. Clinical Genetics, 84, 160166.
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010). EdgeR: A bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 26, 139140.
Sagawa, N., Yura, S., Itoh, H., Mise, H., Kakui, K., Korita, D., . . . Fujii, S. (2002). Role of leptin in pregnancy – a review. Placenta, 23(Suppl. A), S20–S26.
Schrey, S., Kingdom, J., Baczyk, D., Fitzgerald, B., Keating, S., Ryan, G., & Drewlo, S. (2013). Leptin is differentially expressed and epigenetically regulated across monochorionic twin placenta with discordant fetal growth. Molecular Human Reproduction, 19, 764772.
Sierra-Honigmann, M. R., Nath, A. K., Murakami, C., García-Cardeña, G., Papapetropoulos, A., Sessa, W. C., . . . Flores-Riveros, J. R. (1998). Biological action of leptin as an angiogenic factor. Science, 281, 16831686.
Simonazzi, G., Curti, A., Cattani, L., Rizzo, N., & Pilu, G. (2013). Outcome of severe placental insufficiency with abnormal umbilical artery doppler prior to fetal viability. BJOG-an International Journal of Obstetrics and Gynaecology, 120, 754757.
Sitras, V., Paulssen, R., Leirvik, J., Vartun, A., & Acharya, G. (2009). Placental gene expression profile in intrauterine growth restriction due to placental insufficiency. Reproductive Sciences, 16, 701711.
Sood, R., Zehnder, J. L., Druzin, M. L., & Brown, P. O. (2005). Gene expression patterns in the human placenta. Proceedings of the National Academy of Sciences of the United States of America, 103, 54785483.
Spornraft, M., Kirchner, B., Haase, B., Benes, V., Pfaffl, M. W., & Riedmaier, I. (2014). Optimization of extraction of circulating RNAs from plasma – enabling small RNA sequencing. PLoS One, 9, e107259.
Talavera-Adame, D., Xiong, Y., Zhao, T., Arias, A. E., Sierra-Honigmann, M. R., & Farkas, D. L. (2008). Quantitative and morphometric evaluation of the angiogenic effects of leptin. Journal of Biomedical Optics, 13, 064017.
Tsui, N. B., Jiang, P., Wong, Y. F., Leung, T. Y., Chan, K. C., Chiu, R. W., . . . Lo, Y. M. (2014). Maternal plasma RNA sequencing for genome-wide transcriptomic profiling and identification of pregnancy-associated transcripts. Clinical Chemistry, 60, 954962.
Valsky, D. V., Eixarch, E., Martinez, J. M., Crispi, F., & Gratacos, E. (2010). Selective intrauterine growth restriction in monochorionic twins: Pathophysiology, diagnostic approach and management dilemmas. Seminars in Fetal & Neonatal Medicine, 15, 342348.
Valsky, D. V., Eixarch, E., Martinez, J. M., & Gratacós, E. (2010). Selective intrauterine growth restriction in diamniotic twin pregnancies. Prenatal Diagnosis, 30, 719726.
Wang, G., Scott, W. K., Whitehead, P., Court, B. L., Kovach, J. L., Schwartz, S. G., . . . Pericak-Vance, M. A. (2011). A novel ARMS2 splice variant is identified in human retina. Experimental Eye Research, 94, 187191.
Yu, C. C., Furukawa, M., Kobayashi, K., Shikishima, C., Cha, P. C., Sese, J., . . . Toda, T. (2012). Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels. PLoS One, 7, e47081.

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