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Familial Hydatidiform Molar Pregnancy: The Germline Imprinting Defect Hypothesis?

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Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY,volume 301)

Abstract

Imprinting is the uniparental expression of a set of genes. Somatic cells carry two haploid sets of chromosomes, one maternal and one paternal, while germ cells contain only one of the two forms of chromosomes, male or female. This implies that during early embryogenesis the cells committed for developing the future germ cell lineage, the primordial germ cells, which are diploid, have to undergo a total chromosome reprogramming process. This process is delicately controlled during gametogenesis to ensure that males and females have only their respective form of gametes. The machinery involved in this process is yet poorly defined. Familial hydatidiform molar (HM) pregnancy is an abnormal form of pregnancy characterized by hydropic degeneration of placental villi and abnormal, or absence of, embryonic development. To date, the molecular defect causing this condition is unknown. However, in a few studied cases, the presence of paternal methylation patterns on the maternal chromosomes was observed. In this chapter, we summarize what is known about methylation aberrations in HMs and examine more closely the proposed hypothesis of a maternal germline imprinting defect.

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References

  • Agarwal P, Bagga R, Jain V, Karla J, Gopalan S (2004) Familial recurrent molar pregnancy: a case report. Acta Obstet Gynecol Scand 83:218–219

    Article  Google Scholar 

  • Al-Hussaini TK, Abd el-Aal DM, Van den Veyver IB (2003) Recurrent pregnancy loss due to familial and non-familial habitual molar pregnancy. Int J Gynaecol Obstet 83:179–186

    Article  CAS  PubMed  Google Scholar 

  • Ambani LM, Vaidya RA, Rao CS, Daftary SD, Motashaw ND (1980) Familial occurrence of trophoblastic disease—report of recurrent molar pregnancies in sisters in three families. Clin Genet 18:27–29

    CAS  PubMed  Google Scholar 

  • Ariel I, de Groot N, Hochberg A (2000) Imprinted H19 gene expression in embryogenesis and human cancer: the oncofetal connection. Am J Med Genet 91:46–50

    Article  CAS  PubMed  Google Scholar 

  • Barton SC, Surani MA, Norris ML (1984) Role of paternal and maternal genomes in mouse development. Nature 311:374–376

    CAS  PubMed  Google Scholar 

  • Batorfi J, Ye B, Mok SC, Cseh I, Berkowitz RS, Fulop V (2003) Protein profiling of complete mole and normal placenta using ProteinChip analysis on laser capture microdissected cells. Gynecol Oncol 88:424–428

    Article  CAS  PubMed  Google Scholar 

  • Beaujean N, Taylor J, Gardner J, Wilmut I, Meehan R, Young L (2004) Effect of limited DNA methylation reprogramming in the normal sheep embryo on somatic cell nuclear transfer. Biol Reprod 71:185–193

    Article  CAS  PubMed  Google Scholar 

  • Benchaib M, Braun V, Ressnikof D, Lornage J, Durand P, Niveleau A, Guerin JF (2005) Influence of global sperm DNA methylation on IVF results. Hum Reprod 20:768–773

    Article  CAS  PubMed  Google Scholar 

  • Bonilla-Musoles F (1993) The diagnosis of gestational trophoblastic neoplasm by ultrasonography. In: Chervenak FA, Campbell S (eds) Ultrasound in obstetrics and gynecology, vol. 2. Little Brown and Company, Boston, pp 1665–1673

    Google Scholar 

  • Chen T, Zhang YL, Jiang Y, Liu SZ, Schatten H, Chen DY, Sun QY (2004) The DNA methylation events in normal and cloned rabbit embryos. FEBS Lett 578:69–72

    Article  CAS  PubMed  Google Scholar 

  • Copeland LJ (1993) Gestational trophoblastic neoplasia. In: Copeland LJ (ed) Textbook of gynecology. W.B. Saunders Company, Philadelphia, pp 1133–1151

    Google Scholar 

  • Cui H, Niemitz EL, Ravenel JD, Onyango P, Brandenburg SA, Lobanenkov VV, Feinberg AP (2001) Loss of imprinting of insulin-like growth factor-II in Wilms’ tumor commonly involves altered methylation but not mutation of CTCF or its binding site. Cancer Res 61:4947–4950

    CAS  PubMed  Google Scholar 

  • Durand S, Abadie P, Angeletti S, Genti-Raimondi S (2003) Identification of multiple differentially expressed messenger RNAs in normal and pathological trophoblast. Placenta 24:209–218

    Article  CAS  PubMed  Google Scholar 

  • El-Maarri O (2004) SIRPH analysis: SNuPE with IP-RP-HPLC for quantitative measurements of DNA methylation at specific CpG sites. Methods Mol Biol 287:195–205

    CAS  PubMed  Google Scholar 

  • El-Maarri O, Herbiniaux U, Walter J, Oldenburg J (2002) A rapid, quantitative, nonradioactive bisulfite-SNuPE-IP RP HPLC assay for methylation analysis at specific CpG sites. Nucleic Acids Res 30:e25

    Article  PubMed  Google Scholar 

  • El-Maarri O, Seoud M, Coullin P, Herbiniaux U, Oldenburg J, Rouleau G, Slim R (2003) Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles. Hum Mol Genet 12:1405–1413

    Article  CAS  PubMed  Google Scholar 

  • El-Maarri O, Seoud M, Riviere JB, Oldenburg J, Walter J, Rouleau G, Slim R (2005) Patients with familial biparental hydatidiform moles have normal methylation at imprinted genes. Eur J Hum Genet 13:486–490

    Article  CAS  PubMed  Google Scholar 

  • Fallahian M (2003) Familial gestational trophoblastic disease. Placenta 24:797–799

    Article  CAS  PubMed  Google Scholar 

  • Ferguson-Smith AC, Surani MA (2001) Imprinting and the epigenetic asymmetry between parental genomes. Science 293:1086–1089

    Article  CAS  PubMed  Google Scholar 

  • Fisher RA, Khatoon R, Paradinas FJ, Roberts AP, Newlands ES (2000) Repetitive complete hydatidiform mole can be biparental in origin and either male or female. Hum Reprod 15:594–598

    Article  CAS  PubMed  Google Scholar 

  • Fisher RA, Hodges MD, Rees HC, Sebire NJ, Seckl MJ, Newlands ES, Genest DR, Castrillon DH (2002) The maternally transcribed gene p57(KIP2) (CDNK1C) is abnormally expressed in both and rogenetic and biparental complete hydatidiform moles. Hum Mol Genet 11:3267–3272

    Article  CAS  PubMed  Google Scholar 

  • Fisher RA, Hodges MD, Newlands ES (2004) Familial recurrent hydatidiform mole: a review. J Reprod Med 49:595–601

    PubMed  Google Scholar 

  • Fournier C, Goto Y, Ballestar E, Delaval K, Hever AM, Esteller M, Feil R (2002) Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. EMBO J 21:6560–6570

    Article  CAS  PubMed  Google Scholar 

  • Fukunaga M (2000) Early partial hydatidiform mole: prevalence, histopathology, DNA ploidy, and persistence rate. Virchows Arch 437:180–184

    Article  CAS  PubMed  Google Scholar 

  • Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MA (2002) Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 117:15–23

    Article  CAS  PubMed  Google Scholar 

  • Hodges MD, Rees HC, Seckl MJ, Newlands ES, Fisher RA (2003) Genetic refinement and physical mapping of a biparental complete hydatidiform mole locus on chromosome 19q13.4. J Med Genet 40:e95

    Article  CAS  PubMed  Google Scholar 

  • Jaenisch R (2004) Human cloning—the science and ethics of nuclear transplantation. N Engl J Med 351:2787–2791

    Article  CAS  PubMed  Google Scholar 

  • Judson H, Hayward BE, Sheridan E, Bonthron DT (2002) A global disorder of imprinting in the human female germ line. Nature 416:539–542

    CAS  PubMed  Google Scholar 

  • Kang YK, Koo DB, Park JS, Choi YH, Chung AS, Lee KK, Han YM (2001) Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet 28:173–177

    Article  CAS  PubMed  Google Scholar 

  • Kato HD, Terao Y, Ogawa M, Matsuda T, Arima T, Kato K, Yong Z, Wake N (2002) Growth-associated gene expression profiles by microarray analysis of trophoblast of molar pregnancies and normal villi. Int J Gynecol Pathol 21:255–260

    CAS  PubMed  Google Scholar 

  • Kim SJ, Park SE, Lee C, Lee SY, Kim IH, An HJ, Oh YK (2003) Altered imprinting, promoter usage, and expression of insulin-like growth factor-II gene in gestational trophoblastic diseases. Gynecol Oncol 88:411–418

    Article  CAS  PubMed  Google Scholar 

  • Kircheisen R, Schroeder-Kurth T (1991) Familial hydatidiform mole syndrome and genetic aspects of this disturbed trophoblast development. Geburtshilfe Frauenheilkd 51:569–571

    CAS  PubMed  Google Scholar 

  • Kovacs BW, Shahbahrami B, Tast DE, Curtin JP (1991) Molecular genetic analysis of complete hydatidiform moles. Cancer Genet Cytogenet 54:143–152

    Article  CAS  PubMed  Google Scholar 

  • La Vecchia C, Franceschi S, Fasoli M, Mangioni C (1982) Gestational trophoblastic neoplasms in homozygous twins. Obstet Gynecol 60:250–252

    PubMed  Google Scholar 

  • Li E (2002) Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3:662–673

    Article  CAS  PubMed  Google Scholar 

  • Li HW, Tsao SW, Cheung AN (2002) Current understandings of the molecular genetics of gestational trophoblastic diseases. Placenta 23:20–31

    Article  PubMed  Google Scholar 

  • Lindor NM, Ney JA, Gaffey TA, Jenkins RB, Thibodeau SN, Dewald GW (1992) A genetic review of complete and partial hydatidiform moles and nonmolar triploidy. Mayo Clin Proc 67:791–799

    CAS  PubMed  Google Scholar 

  • Maegawa S, Yoshioka H, Itaba N, Kubota N, Nishihara S, Shirayoshi Y, Nanba E, Oshimura M (2001) Epigenetic silencing of PEG3 gene expression in human glioma cell lines. Mol Carcinog 31:1–9

    Article  CAS  PubMed  Google Scholar 

  • Moglabey YB, Kircheisen R, Seoud M, El Mogharbel N, Van den Veyver I, Slim R (1999) Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum Mol Genet 8:667–671

    Article  CAS  PubMed  Google Scholar 

  • Moulton T, Crenshaw T, Hao Y, Moosikasuwan J, Lin N, Dembitzer F, Hensle T, Weiss L, McMorrow L, Loew T, Kraus W, Gerald W, Tycko B (1994) Epigenetic lesions at the H19 locus inWilms’ tumour patients. Nat Genet 7:440–447

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa H, Chadwick RB, Peltomäki P, Plass C, Nakamura Y, de la Chapelle A (2001) Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites on colorectal cancer. Proc Natl Acad Sci USA 98:591–596

    Article  CAS  PubMed  Google Scholar 

  • Narayan H, Mansour P, McDougall WW (1992) Recurrent consecutive partial molar pregnancy. Gynecol Oncol 46:122–127

    Article  CAS  PubMed  Google Scholar 

  • Neumann H (1980) Case report of recurring hydatidiform mole. Geburtshilfe Frauenheilkd 40:385–388

    CAS  PubMed  Google Scholar 

  • Ohlsson R, Flam F, Fisher R, Miller S, Cui H, Pfeifer S, Adam GI (1999) Random monoallelic expression of the imprinted IGF2 and H19 genes in the absence of discriminative parental marks. Dev Genes Evol 209:113–119

    Article  CAS  PubMed  Google Scholar 

  • Olvera M, Harris S, Amezcua CA, McCourty A, Rezk S, Koo C, Felix JC, Brynes RK (2001) Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease. Mod Pathol 14:1036–1042

    Article  CAS  PubMed  Google Scholar 

  • Ozalp S, Yalcin OT, Tanir HM, Etiz E (2001) Recurrent molar pregnancy: report of a case with seven consecutive hydatidiform moles. Gynecol Obstet Invest 52:215–216

    CAS  PubMed  Google Scholar 

  • Parazzini F, La Vecchia C, Franceschi S, Mangili G (1984) Familial trophoblastic disease: case report. Am J Obstet Gynecol 149:382–383

    CAS  PubMed  Google Scholar 

  • Patek E, Johnson P (1978) Recurrent hydatidiform mole. Report of a case with five recurrences. Acta Obstet Gynecol Scand 57:381–383

    CAS  PubMed  Google Scholar 

  • Sensi A, Gualandi F, Pittalis MC, Calabrese O, Falciano F, Maestri I, Bovicelli L, Calzolari E (2000) Mole maker phenotype: possible narrowing of the candidate region. Eur J Hum Genet 8:641–644

    Article  CAS  PubMed  Google Scholar 

  • Seoud M, Khalil A, Frangieh A, Zahed L, Azar G, Nuwayri-Salti N (1995) Recurrent molar pregnancies in a family with extensive intermarriage: report of a family and review of the literature. Obstet Gynecol 86:692–695

    Article  CAS  PubMed  Google Scholar 

  • Slim R, Fallahian M, Riviere JB, Zali MR (2005) Evidence of a genetic heterogeneity of familial hydatidiform moles. Placenta 26:5–9

    Article  CAS  PubMed  Google Scholar 

  • Steenman MJ, Rainier S, Dobry CJ, Grundy P, Horon IL, Feinberg AP (1994) Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms’ tumor. Nat Genet 7:433–439

    Article  CAS  PubMed  Google Scholar 

  • Tamaru H, Selker EU (2001) Ahistone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414:277–283

    Article  CAS  PubMed  Google Scholar 

  • Taniguchi T, Sullivan MJ, Ogawa O, Reeve AE (1995) Epigenetic changes encompassing the IGF2/H19 locus associated with relaxation of IGF2 imprinting and silencing of H19 in Wilms tumor. Proc Natl Acad Sci USA 93:2159–2163

    Google Scholar 

  • Thavarasah AS, Kanagalingam S (1988) Recurrent hydatidiform mole: a report of a patient with 7 consecutive moles. Aust N Z J Obstet Gynaecol 28:233–235

    CAS  PubMed  Google Scholar 

  • Tuncer ZS, Bernstein MR, Wang J, Goldstein DP, Berkowitz RS (1999) Repetitive hydatidiform mole with different male partners. Gynecol Oncol 75:224–226

    Article  CAS  PubMed  Google Scholar 

  • Walter J, Reik W (2001) Genomic imprinting: parental influence on the genome. Nat Rev Genet 2:21–32

    PubMed  Google Scholar 

  • Xue WC, Chan KY, Feng HC, Chiu PM, Ngan HY, Tsao SW, Cheung AN (2004) Promoter hypermethylation of multiple genes in hydatidiform mole and choriocarcinoma. J Mol Diagn 6:326–334

    CAS  PubMed  Google Scholar 

  • Yamazaki Y, Mann MR, Lee SS, Marh J, McCarrey JR, Yanagimachi R, Bartolomei MS (2003) Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc Natl Acad Sci U S A 100:12207–12212

    Article  CAS  PubMed  Google Scholar 

  • Zaragoza MV, Keep D, Genest DR, Hassold T, Redline RW (1997) Early complete hydatidiform moles contain inner cell mass derivatives. Am J Med Genet 70:273–277

    Article  CAS  PubMed  Google Scholar 

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El-Maarri, O., Slim, R. (2006). Familial Hydatidiform Molar Pregnancy: The Germline Imprinting Defect Hypothesis?. In: Doerfler, W., Böhm, P. (eds) DNA Methylation: Basic Mechanisms. Current Topics in Microbiology and Immunology, vol 301. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-31390-7_8

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