Expression of Key Steroidogenic Enzymes in Human Placenta and Associated Adverse Pregnancy Outcomes

Cao, Jiasong; Wang, Yixin; Wang, Shuqi; Shen, Yongmei; Li, Wen; Zhuo, Wei; Li, Shanshan; Lin, Qimei; Chang, Ying

doi:10.1097/fm9.0000000000000167

Cited by 2 publications

(2 citation statements)

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“…In the human placenta, the CYP11A1 protein is uniquely expressed on the syncytiotrophoblast, remaining constant during the whole pregnancy, and tightly regulated by LBP proteins that are the activators and repressors of CYP11A1 protein 38 . The CYP11A1 has been reported to be related to adverse pregnancy outcomes 39 . Based on previous studies, CYP11A1 was increased in the placentas of women with preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

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Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

Shi,

Zhou,

Cai

et al. 2023

The FASEB Journal

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Fetal growth restriction (FGR) is associated with increased susceptibility to perinatal morbidity and mortality. Evidence suggests that epigenetic changes play critical roles in the regulation of fetal growth. We sought to present a comprehensive analysis of the associations between placental DNA methylation and selective fetal growth restriction (sFGR), which is a severe complication of monochorionic twin pregnancies, characterized by one fetus experiencing restricted growth. Genome‐wide methylation analysis was performed on 24 placental samples obtained from 12 monochorionic twins with sFGR (Cohort 1) using Illumina Infinium MethylationEPIC BeadChip. Integrative analysis of our EPIC data and two previous placental methylation studies of sFGR (a total of 30 placental samples from 15 sFGR twins) was used to identify convincing differential promoter methylation. Validation analysis was performed on the placentas from 15 sFGR twins (30 placental samples), 15 FGR singletons, and 14 control singletons (Cohort 2) using pyrosequencing, quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry (IHC). A globe shift toward hypomethylation was identified in the placentas of growth‐restricted fetuses compared with the placentas of normal fetuses in monochorionic twins, including 5625 hypomethylated CpGs and 452 hypermethylated CpGs, especially in the regions of CpG islands, gene‐body and promoters. The analysis of pathways revealed dysregulation primarily in steroid hormone biosynthesis, metabolism, cell adhesion, signaling transduction, and immune response. Integrative analysis revealed a differentially methylated promoter region in the CYP11A1 gene, encoding a rate‐limiting enzyme of steroidogenesis converting cholesterol to pregnenolone. The CYP11A1 gene was validated to have hypomethylation and higher mRNA expression in sFGR twins and FGR singletons. In conclusion, our findings suggested that the changes in placental DNA methylation pattern in sFGR may have functional implications for differentially methylated genes and regulatory regions. The study provides reliable evidence for identifying abnormally methylated CYP11A1 gene in the placenta of sFGR.

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Section: Discussionmentioning

confidence: 99%

“…38 The CYP11A1 has been reported to be related to adverse pregnancy outcomes. 39 Based on previous studies, CYP11A1 was increased in the placentas of women with preeclampsia. In line with upregulated expression of CYP11A1, the production of progesterone and lipid peroxides is increased in placentas of preeclampsia.…”

Section: Genesmentioning

confidence: 98%

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

Shi,

Zhou,

Cai

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

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The central role of creatine and polyamines in fetal growth restriction

Di Giorgio,

Xodo,

Orsaria

et al. 2024

The FASEB Journal

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Placental insufficiency often correlates with fetal growth restriction (FGR), a condition that has both short‐ and long‐term effects on the health of the newborn. In our study, we analyzed placental tissue from infants with FGR and from infants classified as small for gestational age (SGA) or appropriate for gestational age (AGA), performing comprehensive analyses that included transcriptomics and metabolomics. By examining villus tissue biopsies and 3D trophoblast organoids, we identified significant metabolic changes in placentas associated with FGR. These changes include adaptations to reduced oxygen levels and modifications in arginine metabolism, particularly within the polyamine and creatine phosphate synthesis pathways. Specifically, we found that placentas with FGR utilize arginine to produce phosphocreatine, a crucial energy reservoir for ATP production that is essential for maintaining trophoblast function. In addition, we found polyamine insufficiency in FGR placentas due to increased SAT1 expression. SAT1 facilitates the acetylation and subsequent elimination of spermine and spermidine from trophoblasts, resulting in a deficit of polyamines that cannot be compensated by arginine or polyamine supplementation alone, unless SAT1 expression is suppressed. Our study contributes significantly to the understanding of metabolic adaptations associated with placental dysfunction and provides valuable insights into potential therapeutic opportunities for the future.

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Expression of Key Steroidogenic Enzymes in Human Placenta and Associated Adverse Pregnancy Outcomes

Cited by 2 publications

References 100 publications

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

The central role of creatine and polyamines in fetal growth restriction

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