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Deciphering the Epigenetic Landscape: Placental Development and Its Role in Pregnancy Outcomes

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Abstract

The placenta stands out as a unique, transitory, and multifaceted organ, essential to the optimal growth and maturation of the fetus. Functioning as a vital nexus between the maternal and fetal circulatory systems, it oversees the critical exchange of nutrients and waste. This exchange is facilitated by placental cells, known as trophoblasts, which adeptly invade and remodel uterine blood vessels. Deviations in placental development underpin a slew of pregnancy complications, notably fetal growth restriction (FGR), preeclampsia (PE), recurrent spontaneous abortions (RSA), and preterm birth. Central to placental function and development is epigenetic regulation. Despite its importance, the intricate mechanisms by which epigenetics influence the placenta are not entirely elucidated. Recently, the scientific community has turned its focus to parsing out the epigenetic alterations during placental development, such as variations in promoter DNA methylation, genomic imprints, and shifts in non-coding RNA expression. By establishing correlations between epigenetic shifts in the placenta and pregnancy complications, researchers are unearthing invaluable insights into the biology and pathophysiology of these conditions. This review seeks to synthesize the latest findings on placental epigenetic regulation, spotlighting its crucial role in shaping fetal growth trajectories and development. Through this lens, we underscore the overarching significance of the placenta in the larger narrative of gestational health.

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Data Availability

Data availability is not applicable to this article as no new data were created or analyzed in this study.

Abbreviations

ACE :

Angiotensin-converting enzyme

AV :

Arteriovenous

CTBs :

Cytotrophoblasts

CuZn–SOD :

Antioxidant copper-zinc superoxide dismutase

C14MC :

Chromosome 14 miRNA cluster

C19MC :

Chromosome 19 miRNA cluster

DMRs :

Differentially methylated regions

dNK :

Decidual natural killer

ECM :

Extracellular matrix

EG-VEGF :

Endocrine gland-derived vascular endothelial growth factor

EIcircRNA :

Exonic circRNA

ESCd :

BAP treated hESC

EVTs :

Extravillous trophoblasts

EZH2 :

Enhancer of Zeste Homolog 2

FASLG :

FAS ligand

FGR :

Fetal growth restriction

GDM :

Gestational diabetes mellitus

GLUTs :

Glucose transporter proteins

GNG7 :

G protein γ 7

hCG :

Human chorionic gonadotropin

HDACs :

Histone deacetylases

hESCs :

Human embryonic stem cells

HLA :

Human leukocyte antigen

HMTs :

Histone methyltransferases

HNE :

4-Hydroxynonenal

HO-1 :

Heme oxygenase-1

hTSCs :

Human pluripotent stem cells

MHC :

Major histocompatibility complex

MMPs :

Matrix metalloproteinases

Nrf2 :

Nuclear factor erythroid 2-like protein 2

PE :

Preeclampsia

PlGF :

Placental Growth Factor

RSA :

Recurrent spontaneous abortions

SCNT :

Somatic cell nuclear transfer

sEng :

Soluble endoglin

sFlt-1 :

Soluble fms-like tyrosine kinase-1

Slc38a2 :

Sodium-coupled neutral amino acid transporter 2

STBs :

Syncytiotrophoblasts

TET2/TET3 :

DNA demethylases

TIMPs :

Matrix metalloproteinases tissue inhibitors

TGF :

Transforming growth factor

TRAF6 :

Tumor necrosis factor receptor-associated factor 6

TWEAK :

Tumor necrosis factor-like weak inducer of apoptosis

uNK :

Uterine natural killer cells

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Funding

This study was supported by the Key Project on the Integration of Industry, Education and Research Collaborative Innovation of Fujian Province (No. 2021YZ034011), the Key Project on Science and Technology Program of Fujian Health Commission (No. 2021ZD01002),the Joint Funds for the Innovation of Science and Technology, Fujian Province (No: 2021Y9185),the Province-level special subsidy funds for health in Fujian Province (No: Fujian Finance Index [2019] 827),the Fujian Province health scientific research personnel training project(No: Fujian Finance Index [2021] 55),the Fujian Province health scientific research personnel training project(No: Fujian Finance Index [2021] 500).

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Authors and Affiliations

  1. Medical Research Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

    Yujia Chen, Zhoujie Ye, Liping Zhu & Xinrui Wang

  2. National Health Commission (NHC), Key Laboratory of Technical Evaluation of Fertility Regulation for Non-Human Primate, Fujian Maternity and Child Health Hospital, Fuzhou, China

    Yujia Chen, Zhoujie Ye, Liping Zhu & Xinrui Wang

  3. Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect, Fuzhou, China

    Liangpu Xu

  4. Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China

    Meijia Lin

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  1. Yujia Chen
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  2. Zhoujie Ye
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YC and ZY write of the manuscript, ML and LZ made diagrams of the manuscript, XW and LX made revisions to the manuscript.

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Correspondence to Liangpu Xu or Xinrui Wang.

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Chen, Y., Ye, Z., Lin, M. et al. Deciphering the Epigenetic Landscape: Placental Development and Its Role in Pregnancy Outcomes. Stem Cell Rev and Rep (2024). https://doi.org/10.1007/s12015-024-10699-2

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