OBSTETRICS AND GYNAECOLOGY / BASIC RESEARCH
Placental DNA methylation in caesarean sections – a pilot study
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1
First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Warsaw, Poland
2
Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland
3
Second Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Warsaw, Poland
4
Department of Obstetrics and Gynaecology, W. Orlowski Teaching Hospital of Warsaw, Warsaw, Poland
5
Institute of Statistics and Demography, Collegium of Economic Analysis, SGH Warsaw School of Economics, Warsaw, Poland
Submission date: 2020-01-22
Final revision date: 2020-03-28
Acceptance date: 2020-04-08
Online publication date: 2020-05-18
Publication date: 2026-01-16
Corresponding author
Aneta Słabuszewska-Jóźwiak
First Department
of Obstetrics
and Gynaecology
Centre of Postgraduate
Medical Education
90 Żelazna St
01-004 Warsaw, Poland
Phone: +48 504 187-297
Arch Med Sci 2025;21(6):2733-2740
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Caesarean section (CS) is the most common medical procedure performed in women all over the world. There is a hypothesis that caesarean section changes DNA methylation, and it has been linked to immune-mediated diseases such as diabetes in late infant health outcomes. The aim of the study was to evaluate the relationship between caesarean section and DNA methylation patterning in the placenta by measurement of global DNA methylation.
Material and methods:
We included in the study 111 healthy, pregnant women in singular pregnancy at term of delivery (gestational age at least 37 weeks). The study involved global methylation in placental tissue from 46 pregnant women, delivered by vaginal route, and 49 pregnant women, delivered by elective caesarean section (ECS) before the start of labour. In 16 of the elective caesarean section cases, regular uterine contractions were declared. An ELISA-based kit was used for an assessment of the global DNA methylation.
Results:
Global DNA methylation in the placenta in elective caesarean sections (3.02 on average) was significantly lower compared to intrapartum caesarean sections (3.71 on average) and vaginal deliveries (3.64 on average), but did not significantly differ between intrapartum caesarean sections and vaginal deliveries. Global DNA methylation in the placenta in male newborns was significantly higher (4.86 on average) than in female newborns (3.31 on average) in vaginal deliveries but not in either elective or intrapartum caesarean sections.
Conclusions:
Caesarean sections performed without uterine contractions significantly influenced global DNA methylation in the placenta. Moreover, a sexual dimorphism at the level of placental global DNA methylation was demonstrated. Further studies investigating different panels of genes may help to identify genes with aberrant methylation in newborn infants delivered by caesarean section compared to vaginal delivery, as well as demonstrate sexual dimorphism.
REFERENCES (38)
1.
Cartwright JE, Fraser R, Leslie R, Wallace AE, James JL. Remodeling at the maternal – fetal interface: relevance to human pregnancy disorders. Reproduction 2010; 140: 803-13.
2.
Hajkova P. Epigenetic reprogramming – taking a lesson from the embryo. Curr Opin Cell Biol 2010; 22: 342-50.
3.
Hajkova P, Jeffries SJ, Lee C, Miller N, Jackson SP, Surani MA. Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway. Science 2010; 329: 78-82.
4.
Bianco-Miotto T, Mayne BT, Buckberry S, Breen J, Rodriguez Lopez CM, Roberts CT. Recent progress towards understanding the role of DNA methylation in human placental development. Reproduction 2016; 152: 23-30.
5.
Vlahos A, Mansell T, Saffery R, Novakovic B. Human placental methylome in the interplay of adverse placental health, environmental exposure, and pregnancy outcome. PLoS Genet 2019; 15: e1008236.
6.
Almgren M, Schlinzig T, Gomez-Cabrero D, et al. Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health? Am J Obstet Gynecol 2014; 211: e1-7.
7.
Dahlen HG, Kennedy HP, Anderson CM, et al. The EPIIC hypothesis: intrapartum effects on the neonatal epigenome and consequent health outcomes. Med Hypotheses 2013; 80: 656-62.
8.
Chu S, Zhang Y, Jiang Y, et al. Cesarean section without medical indication and risks of childhood allergic disorder, attenuated by breastfeeding. Sci Rep 2017; 7: 9762.
9.
Hansen AK, Wisborg K, Uldbjerg N, Henriksen TB. Risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study. BMJ 2008; 336: 85-7.
10.
Kristensen K, Henriksen L. Cesarean section and disease associated with immune function. J Allergy Clin Immunol 2016; 37: 587-90.
11.
Keag OE, Norman JE, Stock SJ. Long-term risks and benefits associated with cesarean delivery for mother, baby, and subsequent pregnancies: systematic review and meta-analysis. PLoS Med 2018; 15: e1002494.
12.
Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 2010; 107: 11971-5.
13.
Hon GC. Hawkins RD, Caballero OL, et al. Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer. Genome Res 2012; 22: 246-58.
14.
Babenko O, Kovalchuk I, Metz G. Epigenetic programming of neurodegenerative diseases by an adverse environment. Brain Research 2012; 1444: 96-111.
15.
Kim M. DNA methylation: a cause and consequence of type 2 diabetes. Genom Inform 2019; 17: e38.
16.
van Abeelen AF, de Rooij SR, Osmond C, et al. The sex-specific effects of famine on the association between placental size and later hypertension. Placenta 2011; 32: 694-8.
17.
Boland MJ, Nazor KL, Loring JF. Epigenetic regulation of pluripotency and differentiation. Circ Res 2014; 115: 311-24.
18.
Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012; 13: 484-92.
19.
Nelissen ECM, van Montfoort APA, Dumoulin JCM, Evers JLH. Epigenetics and the placenta. Human Reproduct Update 2011; 17: 397-417.
20.
Morales E, Vilahur N, Salas LA, et al. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy. Int J Epidemiol 2016; 45: 1644-55.
21.
Fa S, Larsen TV, Bilde K, et al. Assessment of global DNA methylation in the first trimester fetal tissues exposed to maternal cigarette smoking. Clin Epigenetics 2016; 8: 128.
22.
Brunst KJ, Tignor N, Just A, et al. Cumulative lifetime maternal stress and epigenome-wide placental DNA methylation in the PRISM cohort. Epigenetics 2018; 13: 665-81.
23.
Alexander J, Teague AM, Chen J, et al. Offspring sex impacts DNA methylation and gene expression in placentae from women with diabetes during pregnancy. PLoS One 2018; 13: e0190698.
24.
Wilson SL, Leavey K, Cox BJ, Robinson WP. Mining DNA methylation alterations towards a classification of placental pathologies. Hum Mol Genet 2018; 27: 135-46.
25.
Chen PY, Chu A, Liao WW, et al. Prenatal growth patterns and birthweight are associated with differential DNA methylation and gene expression of cardiometabolic risk genes in human placentas: a discovery-based approach. Reprod Sci 2018; 25: 523-39.
26.
Schroeder DI, Blair JD, Lott P, et al. The human placenta methylome. Proc Natl Acad Sci USA 2013; 110: 6037-42.
27.
Sobieszkoda D, Czech J, Gablo N, et al. MGMT promoter methylation as a potential prognostic marker for acute leukemia. Arch Med Sci 2017; 13: 1433-41.
28.
Loke YJ, Muggli E, Nguyen L, et al. Time- and sex-dependent associations between prenatal alcohol exposure and placental global DNA methylation. Epigenomics 2018; 10: 981-91.
29.
Basak S, Srinivas V, Duttaroy AK. Bisphenol-A impairs cellular function and alters DNA methylation of stress pathway genes in first trimester trophoblast cells. Reprod Toxicol 2018; 82: 72-9.
30.
Binder NK, Beard SA, Kaitu’u-Lino TJ, Tong S, Hannan NJ, Gardner DK. Paternal obesity in a rodent model affects placental gene expression in a sex-specific manner. Reproduction 2015; 149: 435-44.
31.
Virani S, Dolinoy DC, Halubai S, et al. Delivery type not associated with global methylation at birth. Clin Epigenetics 2012; 4: 8.
32.
Franz MB, Poterauer M, Elhenicky M, et al. Global and single gene DNA methylation in umbilical cord blood cells after elective caesarean: a pilot study. Eur J Obstet Gynecol Reprod Biol 2014; 179: 121-4.
33.
Malin A, Schlinzig T, Gomez-Cabrero D, et al. Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health? Am J Obstet Gynecol 2014; 211: 502.e1-8.
34.
Ghidini A, Salafia CM. Histologic placental lesions in women with recurrent preterm delivery. Acta Obstet Gynecol Scand 2005; 84: 547-50.
35.
Yeganegi M, Watson CS, Martins A, et al. Effect of Lactobacillus Rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor. Am J Obstet Gynecol 2008; 200: 532.e1-8.
36.
Martin E, Smeester L, Bommarito PA, et al. Sexual epigenetic dimorphism in the human placenta: implications for susceptibility during the prenatal period. Epigenomics 2017; 9: 267-78.
37.
Chu T, Bunce K, Shaw P, et al. Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta. PLoS One 2014; 9: e107318.
38.
Santos HP, Bhattacharya A, Martin EM, et al. Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status. Epigenetics 2019; 14: 751-65.