The expression of DNA methyltransferases3A is specifically downregulated in chorionic villi of early embryo growth arrest cases

Gu,Huating; Gao,Jing; Guo,Weiwei; Zhou,Yu; Kong,Qingnuan

doi:10.3892/mmr.2017.6650

The expression of DNA methyltransferases3A is specifically downregulated in chorionic villi of early embryo growth arrest cases

Authors:
- Huating Gu
- Jing Gao
- Weiwei Guo
- Yu Zhou
- Qingnuan Kong
View Affiliations

Affiliations: Department of Physiology and Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong 266071, P.R. China, Department of Reproductive Medicine Center, Qingdao Municipal Hospital, Affiliated to Medical College of Qingdao University, Qingdao, Shandong 266011, P.R. China, Department of Pathology, Yantaishan Hospital, Affiliated to Medical College of Qingdao University, Yantai, Shandong 264001, P.R. China, Department of Pathology, Qingdao Municipal Hospital, Affiliated to Medical College of Qingdao University, Qingdao, Shandong 266011, P.R. China
Published online on: May 30, 2017 https://doi.org/10.3892/mmr.2017.6650
Pages: 591-596
Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the expression pattern of four DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L) in placenta chorionic villi of early embryo growth arrest patients. Chorionic villous specimens were obtained from 40 pregnant patients diagnosed with early embryo growth arrest and 40 healthy women who underwent selective pregnancy termination. Reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blot analysis were performed to characterize the mRNA and protein expression of DNMTs in chorionic villous cells. It was identified, among the four DNMTs, DNMT3B presented the highest level of protein expression in both patient groups. Although the mRNA expressions of the four DNMTs were comparable, the DNMT3A protein was specifically downregulated in patients with early embryo growth arrest. Therefore, the current study suggests that an abnormal decrease in DNMT3A protein levels may be involved in the pathogenesis of early embryo growth arrest.

View Figures

View References

1	Yan J, Fan L, Zhao Y, You L, Wang L, Zhao H, Li Y and Chen ZJ: DYZ1 copy number variation, Y chromosome polymorphism and early recurrent spontaneous abortion/early embryo growth arrest. Eur J Obstet Gynecol Reprod Biol. 159:371–374. 2011. View Article : Google Scholar : PubMed/NCBI
2	Luan L, Zhu X and Ma Y: Study on expression of TGF-β1, MMP-9 and TIMP-1 in the chorionic villi of early embryo growth arrest. Pro Obstetrics Gynecol. 2012.
3	Xiao FZ and Hu ML: The prevent and reason analysis of the patients of embryo damage. China Practical Medicine. 8:27–29. 2013.(In Chinese).
4	Wang Y, Han YF, Wang ZY and Wen-Yuan LI: Clinical study on intervention measures of re-pregnancy in people with embryo damage history. Guide of China Medicine. 19:56–57. 2014.(In Chinese).
5	Bauer MK, Harding JE, Bassett NS, Breier BH, Oliver MH, Gallaher BH, Evans PC, Woodall SM and Gluckman PD: Fetal growth and placental function. Mol Cell Endocrinol. 140:115–120. 1998. View Article : Google Scholar : PubMed/NCBI
6	Beck S and Rakyan VK: The methylome: Approaches for global DNA methylation profiling. Trends Genet. 24:231–237. 2008. View Article : Google Scholar : PubMed/NCBI
7	Oda M, Yamagiwa A, Yamamoto S, Nakayama T, Tsumura A, Sasaki H, Nakao K, Li E and Okano M: DNA methylation regulates long-range gene silencing of an X-linked homeobox gene cluster in a lineage-specific manner. Genes Dev. 20:3382–3394. 2006. View Article : Google Scholar : PubMed/NCBI
8	MacDonald WA and Mann MR: Epigenetic regulation of genomic imprinting from germ line to preimplantation. Mol Reprod Dev. 81:126–140. 2014. View Article : Google Scholar : PubMed/NCBI
9	Watanabe D, Suetake I, Tada T and Tajima S: Stage- and cell-specific expression of DNMT3a and DNMT3b during embryogenesis. Mech Dev. 118:187–190. 2002. View Article : Google Scholar : PubMed/NCBI
10	Koukoura O, Sifakis S and Spandidos DA: DNA methylation in the human placenta and fetal growth (Review). Mol Med Rep. 5:883–889. 2012.PubMed/NCBI
11	O'Doherty AM, Magee DA, O'Shea LC, Forde N, Beltman ME, Mamo S and Fair T: DNA methylation dynamics at imprinted genes during bovine pre-implantation embryo development. BMC Dev Biol. 15:132015. View Article : Google Scholar : PubMed/NCBI
12	Uysal F, Akkoyunlu G and Ozturk S: Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos. Biochimie. 116:103–113. 2015. View Article : Google Scholar : PubMed/NCBI
13	Chen T and Li E: Structure and function of eukaryotic DNA methyltransferases. Curr Top Dev Biol. 60:55–89. 2004. View Article : Google Scholar : PubMed/NCBI
14	Yoder MC, Hiatt K, Dutt P, Mukherjee P, Bodine DM and Orlic D: Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac. Immunity. 7:335–344. 1997. View Article : Google Scholar : PubMed/NCBI
15	Katari S, Turan N, Bibikova M, Erinle O, Chalian R, Foster M, Gaughan JP, Coutifaris C and Sapienza C: DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet. 18:3769–3778. 2009. View Article : Google Scholar : PubMed/NCBI
16	Huang K, Wu Z, Liu Z, Hu G, Yu J, Chang KH, Kim KP, Le T, Faull KF, Rao N, et al: Selective demethylation and altered gene expression are associated with ICF syndrome in human-induced pluripotent stem cells and mesenchymal stem cells. Hum Mol Genet. 23:6448–6457. 2014. View Article : Google Scholar : PubMed/NCBI
17	Ehrlich M: The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease. Clin Immunol. 109:17–28. 2003. View Article : Google Scholar : PubMed/NCBI
18	Arand J, Wossidlo M, Lepikhov K, Peat JR, Reik W and Walter J: Selective impairment of methylation maintenance is the major cause of DNA methylation reprogramming in the early embryo. Epigenetics Chromatin. 8:12015. View Article : Google Scholar : PubMed/NCBI
19	Hirasawa R and Sasaki H: Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation embryos. Gene Expr Patterns. 9:27–30. 2009. View Article : Google Scholar : PubMed/NCBI
20	Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R and Sasaki H: Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes Dev. 22:1607–1616. 2008. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Spradley FT: Metabolic abnormalities and obesity's impact on the risk for developing preeclampsia. Am J Physiol Regul Integr Comp Physiol. 312:R5–R12. 2017. View Article : Google Scholar : PubMed/NCBI
23	Hou SX and Dept U: Application of ultrasound in the diagnosis of intrauterine embryo growth arrest. World Latest Medicine Information. 15:29–30. 2015.(In Chinese).
24	Sharma S: Natural killer cells and regulatory T cells in early pregnancy loss. Int J Dev Biol. 58:219–229. 2014. View Article : Google Scholar : PubMed/NCBI
25	Zobeiri F, Sadrkhanlou RA, Salami S, Mardani K and Ahmadi A: The effect of ciprofloxacin on sperm DNA damage, fertility potential and early embryonic development in NMRI mice. Vet Res Forum. 3:131–135. 2012.PubMed/NCBI
26	Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y and Jinno Y: Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: An HPLC-based study. Ann Hum Genet. 68:196–204. 2004. View Article : Google Scholar : PubMed/NCBI
27	Maccani MA and Marsit CJ: Epigenetics in the placenta. Am J Reprod Immunol. 62:78–89. 2009. View Article : Google Scholar : PubMed/NCBI
28	Hata K, Kusumi M, Yokomine T, Li E and Sasaki H: Meiotic and epigenetic aberrations in Dnmt3L-deficient male germ cells. Mol Reprod Dev. 73:116–122. 2006. View Article : Google Scholar : PubMed/NCBI
29	Yin LJ, Zhang Y, Lv PP, He WH, Wu YT, Liu AX, Ding GL, Dong MY, Qu F, Xu CM, et al: Insufficient maintenance DNA methylation is associated with abnormal embryonic development. BMC Med. 10:262012. View Article : Google Scholar : PubMed/NCBI
30	Lucifero D, La Salle S, Bourc'his D, Martel J, Bestor TH and Trasler JM: Coordinate regulation of DNA methyltransferase expression during oogenesis. BMC Dev Biol. 7:362007. View Article : Google Scholar : PubMed/NCBI
31	Waterland RA and Jirtle RL: Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 20:63–68. 2004. View Article : Google Scholar : PubMed/NCBI
32	Robins JC, Marsit CJ, Padbury JF and Sharma SS: Endocrine disruptors, environmental oxygen, epigenetics and pregnancy. Front Biosci (Elite Ed). 3:690–700. 2011.PubMed/NCBI
33	Sood R, Zehnder JL, Druzin ML and Brown PO: Gene expression patterns in human placenta. Proc Natl Acad Sci USA. 103:5478–5483. 2006. View Article : Google Scholar : PubMed/NCBI
34	Filiberto AC, Maccani MA, Koestler D, Wilhelm-Benartzi C, Avissar-Whiting M, Banister CE, Gagne LA and Marsit CJ: Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta. Epigenetics. 6:566–572. 2011. View Article : Google Scholar : PubMed/NCBI
35	Nelissen EC, van Montfoort AP, Dumoulin JC and Evers JL: Epigenetics and the placenta. Hum Reprod Update. 17:397–417. 2011. View Article : Google Scholar : PubMed/NCBI
36	Vlahović M, Bulić-Jakus F, Jurić-Lekić G, Fucić A, Marić S and Serman D: Changes in the placenta and in the rat embryo caused by the demethylating agent 5-azacytidine. Int J Dev Biol. 43:843–846. 1999.PubMed/NCBI
37	Grazul-Bilska AT, Johnson ML, Borowicz PP, Minten M, Bilski JJ, Wroblewski R, Velimirovich M, Coupe LR, Redmer DA and Reynolds LP: Placental development during early pregnancy in sheep: Cell proliferation, global methylation, and angiogenesis in the fetal placenta. Reproduction. 141:529–540. 2011. View Article : Google Scholar : PubMed/NCBI