DNA Methylation and Expression Profiles of Placenta and Umbilical Cord Blood Reveal the Characteristics of Gestational Diabetes Mellitus Patients and Offspring

Overview

Journal Clin Epigenetics

Publisher Biomed Central

Specialty Genetics

Date 2022 May 23

PMID 35606885

Authors

Sha Lu

Jiahao Wang

Nisile Kakongoma

Wen Hua

Jiahui Xu

Yunfei Wang

Shutao He

Hongcang Gu

Jiantao Shi

Wensheng Hu

Affiliations

Soon will be listed here.

Abstract

Background: Gestational diabetes mellitus (GDM) is a common pregnancy-specific disease and is growing at an alarming rate worldwide, which can negatively affect the health of pregnant women and fetuses. However, most studies are limited to one tissue, placenta or umbilical cord blood, usually with one omics assay. It is thus difficult to systematically reveal the molecular mechanism of GDM and the key influencing factors on pregnant women and offspring.

Results: We recruited a group of 21 pregnant women with GDM and 20 controls without GDM. For each pregnant woman, reduced representation bisulfite sequencing and RNA-seq were performed using the placenta and paired neonatal umbilical cord blood specimens. Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were identified with body mass index as a covariate. Through the comparison of GDM and control samples, 2779 and 141 DMRs, 1442 and 488 DEGs were identified from placenta and umbilical cord blood, respectively. Functional enrichment analysis showed that the placenta methylation and expression profiles of GDM women mirrored the molecular characteristics of "type II diabetes" and "insulin resistance." Methylation-altered genes in umbilical cord blood were associated with pathways "type II diabetes" and "cholesterol metabolism." Remarkably, both DMRs and DEGs illustrated significant overlaps among placenta and umbilical cord blood samples. The overlapping DMRs were associated with "cholesterol metabolism." The top-ranking pathways enriched in the shared DEGs include "growth hormone synthesis, secretion and action" and "type II diabetes mellitus."

Conclusions: Our research demonstrated the epigenetic and transcriptomic alternations of GDM women and offspring. Our findings emphasized the importance of epigenetic modifications in the communication between pregnant women with GDM and offspring, and provided a reference for the prevention, control, treatment, and intervention of perinatal deleterious events of GDM and neonatal complications.

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References

Amri K, Freund N, Duong van Huyen J, Merlet-Benichou C, Lelievre-Pegorier M . Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney. Diabetes. 2001; 50(5):1069-75. DOI: 10.2337/diabetes.50.5.1069. View

Ghaben A, Scherer P . Adipogenesis and metabolic health. Nat Rev Mol Cell Biol. 2019; 20(4):242-258. DOI: 10.1038/s41580-018-0093-z. View

Charlton J, Downing T, Smith Z, Gu H, Clement K, Pop R . Global delay in nascent strand DNA methylation. Nat Struct Mol Biol. 2018; 25(4):327-332. PMC: 5889353. DOI: 10.1038/s41594-018-0046-4. View

Feng H, Conneely K, Wu H . A Bayesian hierarchical model to detect differentially methylated loci from single nucleotide resolution sequencing data. Nucleic Acids Res. 2014; 42(8):e69. PMC: 4005660. DOI: 10.1093/nar/gku154. View

Xu H, Abuhatzira L, Carmona G, Vadrevu S, Satin L, Notkins A . The Ia-2β intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice. Diabetologia. 2015; 58(10):2298-306. PMC: 6754265. DOI: 10.1007/s00125-015-3683-8. View

Ramakrishnan G, Arjuman A, Suneja S, Das C, Chandra N . The association between insulin and low-density lipoprotein receptors. Diab Vasc Dis Res. 2012; 9(3):196-204. DOI: 10.1177/1479164111430243. View

Hanson M, Godfrey K, Lillycrop K, Burdge G, Gluckman P . Developmental plasticity and developmental origins of non-communicable disease: theoretical considerations and epigenetic mechanisms. Prog Biophys Mol Biol. 2011; 106(1):272-80. DOI: 10.1016/j.pbiomolbio.2010.12.008. View

. 2. Classification and Diagnosis of Diabetes: . Diabetes Care. 2019; 43(Suppl 1):S14-S31. DOI: 10.2337/dc20-S002. View

Wang L, Hou Y, Meng D, Yang L, Meng X, Liu F . Vitamin B12 and Folate Levels During Pregnancy and Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis. Front Nutr. 2021; 8:670289. PMC: 8236507. DOI: 10.3389/fnut.2021.670289. View

10.

Xi Y, Li W . BSMAP: whole genome bisulfite sequence MAPping program. BMC Bioinformatics. 2009; 10:232. PMC: 2724425. DOI: 10.1186/1471-2105-10-232. View

11.

Lehto M, Laitinen S, Chinetti G, Johansson M, Ehnholm C, Staels B . The OSBP-related protein family in humans. J Lipid Res. 2001; 42(8):1203-13. View

12.

Petersen M, Shulman G . Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018; 98(4):2133-2223. PMC: 6170977. DOI: 10.1152/physrev.00063.2017. View

13.

Murphy S, Braithwaite E, Hubbard I, Williams K, Tindall E, Holmes E . Salivary cortisol response to infant distress in pregnant women with depressive symptoms. Arch Womens Ment Health. 2014; 18(2):247-253. PMC: 4516861. DOI: 10.1007/s00737-014-0473-0. View

14.

El Hajj N, Pliushch G, Schneider E, Dittrich M, Muller T, Korenkov M . Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes. 2012; 62(4):1320-8. PMC: 3609586. DOI: 10.2337/db12-0289. View

15.

Stiles A, McDonald J, Bauman D, Russell D . CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions. J Biol Chem. 2009; 284(42):28485-9. PMC: 2781391. DOI: 10.1074/jbc.R109.042168. View

16.

Mack L, Tomich P . Gestational Diabetes: Diagnosis, Classification, and Clinical Care. Obstet Gynecol Clin North Am. 2017; 44(2):207-217. DOI: 10.1016/j.ogc.2017.02.002. View

17.

Franke K, Harder T, Aerts L, Melchior K, Fahrenkrog S, Rodekamp E . 'Programming' of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats. Brain Res. 2005; 1031(2):276-83. DOI: 10.1016/j.brainres.2004.11.006. View

18.

Sreekumar R, Halvatsiotis P, Schimke J, Nair K . Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. Diabetes. 2002; 51(6):1913-20. DOI: 10.2337/diabetes.51.6.1913. View

19.

Chang C, Zhang K, Veluchamy A, Hebert H, Looker H, Colhoun H . A Genome-Wide Association Study Provides New Evidence That CACNA1C Gene is Associated With Diabetic Cataract. Invest Ophthalmol Vis Sci. 2016; 57(4):2246-50. PMC: 4855826. DOI: 10.1167/iovs.16-19332. View

20.

Schwartz N, Nachum Z, Green M . The prevalence of gestational diabetes mellitus recurrence--effect of ethnicity and parity: a metaanalysis. Am J Obstet Gynecol. 2015; 213(3):310-7. DOI: 10.1016/j.ajog.2015.03.011. View