Startseite Differentially expressed genes in the placentas with pre-eclampsia and fetal growth restriction using RNA sequencing and verification
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Differentially expressed genes in the placentas with pre-eclampsia and fetal growth restriction using RNA sequencing and verification

  • Haiying Chen ORCID logo , Xiaoqing Li , Xiaoming Xu , Yanjun Hu EMAIL logo und Jianqiong Zheng EMAIL logo
Veröffentlicht/Copyright: 28. April 2025
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Journal of Perinatal Medicine
Aus der Zeitschrift Journal of Perinatal Medicine Band 53 Heft 5

Abstract

Objectives

Pre-eclampsia and fetal growth restriction (FGR) is a serious complication of pregnancy. Our study aimed to identify the DEGs and pathways in the placentas of patients with pre-eclampsia and FGR and investigated the relationships between these genes and clinical characteristics to elucidate the dysregulated placental mechanisms linked to pre-eclampsia and FGR.

Methods

A total of 28 patients were enrolled in the study (6 individuals were selected for RNA sequencing and 22 participants was subjected to qRT-PCR). We used RNA sequencing to identify DEGs and pathways in the placenta. Ten DEGs were verified using qRT-PCR. The relationships between these DEGs and clinical characteristics were investigated using correlation analysis.

Results

We detected significant molecular changes in the placentas of pre-eclampsia and FGR, encompassing diverse biological processes. SYDE1, HTRA1, and PAPPA2 expression was significantly upregulated, whereas MYL9, OLFML3, VTN, and AXNA8 expression was downregulated (p<0.05). The mRNA expression levels of SYDE1, HTRA1 and PAPPA2 displayed a positive correlation with systolic and diastolic blood pressure, LDH and LST, while exhibiting a negative correlation with fetal weight and serum albumin. And the mRNA expression levels of MYL9, OLFML3, VTN, and ANXA8 were significantly negatively correlated with systolic and diastolic blood pressure, LDH and LST, while exhibiting a positive correlation with fetal weight.

Conclusions

Our study found variations in gene expression and pathways in the placenta that may contribute to pre-eclampsia and FGR. Genes expressed in the placenta that are associated with clinical indicators could serve as potential biomarkers for assessing the occurrence of pre-eclampsia and FGR.

Keywords: pre-eclampsia; placenta; fetal growth restriction; RNA sequencing

Introduction

Proper placental function is essential for a successful pregnancy. Placental abnormalities can lead to serious complications such as pre-eclampsia (PE) and fetal growth restriction (FGR), putting both mothers and babies at risk [1], [2], [3]. PE is a severe pregnancy complication characterized by the onset of hypertension, proteinuria, and tissue edema after the 20th week of gestation, and is accompanied by various types of organ damage and secondary adverse impacts on fetal growth [4], 5]. FGR is a condition in which the fetus is affected by pathological factors (maternal, placental, or fetal causes) that hinder its growth potential [6]. FGR is associated with an increased risk of stillbirth, preterm birth, cerebral palsy, and neonatal mortality [7]. The incidence of FGR in the setting of pre-eclampsia ranges from 12.8 to 58.6 %, a rate notably elevated compared to pregnancies in which the mother does not have PE [8], [9], [10], [11].

Placental insufficiency is a significant factor in the pathophysiology of pre-eclampsia and FGR, although the exact underlying causes are not fully understood. Some studies suggest that various factors can lead to inadequate uteroplacental perfusion, resulting in characteristic but variable clinical presentations (hypertension, liver and kidney impairment, hypoproteinaemia or low birth weight) [12], 13]. RNA sequencing is a prominent technique for characterizing and quantifying transcripts in the transcriptome [14]. It is widely used in gene expression discovery, genome annotation, and expression profiling analysis. Quantification of placental gene expression by RNA sequencing can further elucidate the mechanism of pre-eclampsia and FGR and can serve as a preventive, predictive, and therapeutic measure.

In this study, we aimed to identify DEGs and pathways in the placentas of patients with pre-eclampsia and FGR using RNA sequencing. Furthermore, we investigated the relationship between these genes and clinical characteristics to elucidate the dysregulated placental mechanisms linked to pre-eclampsia and FGR (Figure 1).

Figure 1: Dysregulated placental mechanisms linked to pre-eclampsia and FGR. PE: pre-eclampsia; FGR: fetal growth restriction.
Figure 1:

Dysregulated placental mechanisms linked to pre-eclampsia and FGR. PE: pre-eclampsia; FGR: fetal growth restriction.

Materials and methods

Patients and samples

The current study was approved by the Ethics Committee of Wenzhou People’s Hospital. Placentas from patients with pre-eclampsia and FGR and controls were collected via caesarean section at Wenzhou People’s Hospital from July 2021 to September 2022. A total of 28 patients were enrolled in the study, and clinical data and placental samples were obtained. Six individuals were selected for RNA sequencing (three patients with pre-eclampsia and FGR and three healthy controls), and the placental tissue of the remaining 22 participants was subjected to qRT-PCR (10 patients with pre-eclampsia and FGR and 12 healthy controls), as detailed in Tables 1 and 2. The healthy control group was randomly sampled to represent data such as age, BMI and gravidity. Pre-eclampsia diagnosed based on the sudden onset of hypertension occurring after 20 weeks of gestation (twice in a 24-h period, at least 6 h apart, systolic and diastolic blood pressure ≥140 mmHg or ≥90 mmHg), accompanied by at least one additional associated complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction [5], 15]. FGR is characterized by inadequate fetal growth that falls below the genetic potential, as determined by the individual’s genetic composition. This is typically identified through ultrasonography, and the estimated fetal weight (EFW) generally falls below the 10th percentile for the corresponding gestational age [16]. Out of 75 pregnant women who agreed to participate and provided placenta samples, 47 were excluded due to conditions like multiple pregnancies, chronic nephritis, infectious hepatitis, parathyroid disease, polycystic ovary syndrome, gestational diabetes, autoimmune diseases, known fetal abnormalities or abnormal karyotypes, or incomplete clinical records. Prior to the study, all participants were informed of the study objectives, procedures, potential risks, and benefits. Written informed consent was obtained from each participant to ensure their voluntary participation and understanding of the study requirements.

Table 1:

The demographics and clinical characteristics of patients for RNA sequencing.

Analyzed items Control (n=3) PE and FGR (n=3) p-Value
Maternal age, years 27.67 ± 2.08 34.67 ± 4.51 0.07
Gestational age, weeks 38.33 ± 0.58 36.33 ± 0.30 <0.01b
BMI before pregnancy, kg/m2 22.90 ± 1.73 20.81 ± 3.25 0.38
Gravidity 3.33 ± 2.31 2.33 ± 0.58 0.51
Systolic BP, mmHg 118.00 ± 11.27 162.00 ± 14.42 0.01a
Diastolic BP, mmHg 80.33 ± 7.57 100.33 ± 4.73 0.02a
Fetal weight 3783.33 ± 408.57 1940.00 ± 300.50 <0.01b
Proteinuria, mg/24 h – 2349.33 ± 2346.07 <0.01b
ALT, U/L 12.67 ± 6.43 25.34 ± 17.61 0.31
AST, U/L 31.00 ± 16.64 25.33 ± 17.62 0.71
LDH, U/L 156.33 ± 22.50 207.67 ± 57.73 0.23
Albumin 31.37 ± 4.45 28.43 ± 3.28 0.41
Hemoglobin, g/L 108.00 ± 15.72 114.33 ± 17.67 0.67

  1. PE, pre-eclampsia; FGR, fetal growth restriction; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; data presented as mean ± standard error or median (interquartile range). ap<0.05. bp<0.01.

Table 2:

The demographics and clinical characteristics of patients for qRT-PCR.

Analyzed items Control (n=12) PE and FGR

(n=10)		 p-Value
Maternal age, years 29.92 ± 2.71 29.50 ± 3.87 0.77
Gestational age, weeks 38.21 (38.00, 39.00) 36.57 (36.14, 38.43) 0.06
Pre-pregnancy BMI, kg/m2 20.75 ± 2.05 22.81 ± 4.91 0.20
Gravidity 2.67 ± 1.44 2.30 ± 1.49 0.57
Systolic BP, mmHg 115.58 ± 10.28 159.90 ± 7.46 <0.01a
Diastolic BP, mmHg 76.83 ± 7.15 104.50 ± 4.67 <0.01a
Fetal birth weight 3509.17 ± 367.34 2059.00 ± 429.17 <0.01a
Proteinuria, mg/24 h – 2972.5 (1074.75, 6004.00) <0.01a
ALT, U/L 16.67 ± 5.93 20.50 ± 15.04 0.43
AST, U/L 17 (8.5, 19.5) 24 (18.75, 30.75) <0.01a
LDH, U/L 139.50 (128.75, 153) 215 (165, 244.75) <0.01a
Albumin, g/L 34.80 (31.80, 35.93) 25.60 (20.15, 31.18) <0.01a
Hemoglobin, g/L 118.25 ± 11.62 121.70 ± 15.92 0.56

  1. PE, pre-eclampsia; FGR, fetal growth restriction; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; data presented as mean ± standard error or median (interquartile range). ap<0.01.

RNA sequencing

Human placentas were collected from women pre-eclampsia and FGR and from healthy controls in the third trimester of pregnancy [gestational weeks 38 (36.5, 38.68)] at the time of caesarean section and snap-frozen immediately in liquid nitrogen. RNA sequencing and bioinformatic analyses were performed using LC-BIO Technologies (Hangzhou, China). RNA was isolated and purified using the TRIzol reagent (Invitrogen, Carlsbad, CA, USA). The RNA yield of each sample was quantified using NanoDrop ND-1000 (NanoDrop, Wilmington, DE, USA). Finally, we performed 2 × 150 bp paired-end sequencing on an Illumina NovaSeq 6000. Differentially expressed genes (DEGs) were screened according to fold change (FC >2 or <0.5) and p-value (p<0.05).

Bioinformatics analysis of RNA sequencing data

Fastp software was used to remove reads that contained adaptor contaminants, low-quality bases, and undetermined bases using default parameters. StringTie was used to determine the expression levels of mRNAs by calculating the FPKMs. Analysis of protein function based on GO and KEGG pathway annotation was performed. Differentially expressed mRNAs with a fold change >2 or a fold change <0.5 and with a parametric F test comparing nested linear models (p-value <0.05) were selected using the R package edgeR.

Quantitative RT-PCR validation of DEGs

We selected 10 genes from the DEGs for qRT-PCR validation using an extended sample. Total RNA was extracted using TRIzol reagent (Invitrogen, USA), followed by synthesis of total complementary DNA using a commercially available reverse transcription kit (Thermo Scientific). qRT-PCR was performed using SYBR Green PCR Master Mix (Biomake). Primer sequences for the reference gene (GAPDH) were used to normalize mRNA expression levels. The relative mRNA expression levels were determined using the 2−ΔΔCt method. Primer sequences used are listed in Supplementary Table S1.

Statistical analysis

SPSS (version 21.0; IBM, USA) was used to analyze descriptive statistics. Normally distributed data are presented as mean ± standard deviation; non-normally distributed data are presented as median (P25, P75). Chi-square tests were used to determine the significant differences between the groups of women in terms of categorical variables. A two-tailed Student’s t-test was used to analyze differences in mean values, while the Mann-Whitney U test was used when variances were unequal. Pearson’s or Spearman’s correlation coefficients were used to analyze the relationships between mRNA expression levels and the clinical indicators of pre-eclampsia and FGR. Statistical p was set than 0.05.

Results

A total of 28 patients were enrolled in the study, and clinical data and placental samples were obtained. It was observed that systolic and diastolic blood pressure were markedly elevated in patients whose samples were subjected to RNA sequencing, while estimated fetal weight was notably reduced in patients with pre-eclampsia and FGR compared to healthy controls. According to the qRT-PCR data, compared with control participants, individuals with pre-eclampsia and FGR exhibited significantly elevated blood pressure, proteinuria, aspartate transaminase (AST) and lactate dehydrogenase (LDH) levels, and decreased albumin levels and fetal weight (p<0.05). No significant differences were observed between the two groups in terms of maternal age, pre-pregnancy BMI, gravidity, or parity (p>0.05).

The differentially expressed genes differed between patients with pre-eclampsia and FGR and controls

To assess the quality of RNA, the HISAT2 (HISAT2 [https://ccb.jhu.edu/software/hisat]) splicing mapping algorithm was utilized to align reads to the human genome (hg38) following preprocessing. The analysis revealed that more than 95 % of the reads from all samples were successfully mapped, suggesting the reliability of the sequencing results (Supplementary Table S2). Furthermore, principal component analysis (PCA) revealed distinct clustering of the two groups, as depicted in Figure 2A, suggesting notable disparities between the groups.

Figure 2: RNA-seq results for pre-eclampsia and fetal growth restriction patients and controls. (A) Principal component analysis (PCA) of the two groups. (B) DEGs identified in placentas from preeclampsia with severe features and fetal growth restriction and control groups (n=3). (C) Volcano plot of DEGs identified in placentas from preeclampsia and FGR and control groups (n=3). (D) GO analysis results. BP: biological process. CC: cellular component. MF: molecular function. (E) Results of KEGG enrichment analysis.
Figure 2:

RNA-seq results for pre-eclampsia and fetal growth restriction patients and controls. (A) Principal component analysis (PCA) of the two groups. (B) DEGs identified in placentas from preeclampsia with severe features and fetal growth restriction and control groups (n=3). (C) Volcano plot of DEGs identified in placentas from preeclampsia and FGR and control groups (n=3). (D) GO analysis results. BP: biological process. CC: cellular component. MF: molecular function. (E) Results of KEGG enrichment analysis.

To identify DEGs in patients with pre-eclampsia and FGR, we utilized the edgeR software for analysis, resulting in the detection of 208 DEGs, with 78 genes exhibiting upregulated expression and 130 genes showing downregulated expression (Figure 2B and C). The 20 most significantly upregulated and 20 downregulated DEGs are shown in Table 3. To elucidate the predominant biological processes contributing to the differential gene expression profile between the pre-eclampsia and FGR and control groups, GO enrichment analysis was conducted on the 208 identified genes (Figure 2D). The analysis revealed that DEGs were primarily associated with biological processes, cellular components, and molecular functions. Specifically, regarding biological processes, DEGs were found to be involved in signal transduction, G protein-coupled receptor signalling pathways, multicellular biological development, REDOX processes, lipid metabolism processes, angiogenesis, cell differentiation, positive regulation of protein kinase B signalling, and positive regulation of angiogenesis. Furthermore, KEGG pathway analysis demonstrated that the DEGs were primarily associated with neuroactive ligand-receptor interactions, complement and coagulation cascades, fat digestion and absorption, focal adhesion, and cytokine-receptor interactions. Additionally, these genes were involved in the PI3K/Akt signalling pathway, Ras signalling pathway, phagosome, and ECM-receptor interaction pathways (Figure 2E, Supplementary Table S3).

Table 3:

Differential expression genes between pre-eclampsia and fetal growth restriction patients and controls.

Gene_name FC (PE and FGR/Con) log2, FC p-Value
Upregulated
 LEP 23.53 4.56 0.00
 TREM1 19.46 4.28 0.00
 PAPPA2 9.57 3.26 0.00
 HTRA4 7.84 2.97 0.00
 FLT1 4.87 2.28 0.00
 HTRA1 3.05 1.61 0.00
 SH3BP5 3.00 1.58 0.00
 STS 2.67 1.42 0.00
 PROCR 2.64 1.40 0.00
 FLT4 2.57 1.36 0.00
 ADGRG6 2.50 1.32 0.00
 SYDE1 2.49 1.32 0.00
 ENG 2.49 1.31 0.00
 GPT2 2.46 1.30 0.00
 PRRG4 2.32 1.22 0.00
 ADAM12 2.32 1.21 0.00
 SLC6A2 2.32 1.21 0.00
 APOL4 2.28 1.19 0.00
 SLCO2A1 2.25 1.17 0.00
 INHBA 2.25 1.17 0.00
Downregulated
 HSPB6 0.16 −2.67 0.00
 SNRPGP10 0.27 −1.86 0.01
 PROK1 0.28 −1.86 0.00
 CD74 0.29 −1.80 0.00
 CFD 0.29 −1.80 0.00
 ISLR 0.30 −1.73 0.00
 MYL9 0.30 −1.72 0.00
 VTN 0.34 −1.57 0.00
 CD99 0.35 −1.53 0.00
 TPM2 0.35 −1.53 0.01
 MTND4P12 0.35 −1.50 0.01
 OLFML3 0.36 −1.48 0.00
 CD53 0.37 −1.44 0.01
 RPL10P9 0.37 −1.42 0.01
 ANXA8 0.39 −1.35 0.00
 TSC22D3 0.39 −1.34 0.00
 RNASE1 0.40 −1.33 0.01
 RGS2 0.40 −1.32 0.01
 CD68 0.41 −1.30 0.01
 FTL 0.45 −1.17 0.00

  1. PE, pre-eclampsia; FGR, fetal growth restriction.

Validation of representative genes by qRT-PCR

Our previous research revealed notable variations in the transcriptional expression levels of SYDE1, HTRA1, PAPPA2, MYL9, OLFML3, VTN, AXNA8, ISLR, STAB1, and TPM2 in the placentas of patients with pre-eclampsia and FGR compared with healthy controls [17]. To investigate whether these genes were also differentially expressed in patients with pre-eclampsia and FGR compared with controls, qRT-PCR was conducted for further verification. As depicted in Figure 3, the mRNA expression levels of three genes (SYDE1, HTRA1, and PAPPA2) were significantly upregulated in the placentas of patients with pre-eclampsia and FGR, whereas four genes (MYL9, OLFML3, VTN, and ANXA8) displayed significantly downregulated expression (p<0.05), which was consistent with the RNA sequencing data (Supplementary Table S4). The mRNA expression levels of ISLR, STAB1, and TPM2 were not significantly different between women with pre-eclampsia and FGR and healthy controls.

Figure 3: The mRNA lever of 10 DEGs in placental villi from pre-eclampsia and fetal growth restriction patients and controls was evaluated using qRT-PCR (p<0.01).
Figure 3:

The mRNA lever of 10 DEGs in placental villi from pre-eclampsia and fetal growth restriction patients and controls was evaluated using qRT-PCR (p<0.01).

Correlations between the mRNA expression levels of representative genes and the clinical characteristics of patients with pre-eclampsia and FGR

Further analysis was performed to examine the correlation between the mRNA expression levels of genes (SYDE1, HTRA1, PAPPA2, MYL9, OLFML3, VTN, and ANXA8) and clinical features (fetal birth weight, systolic blood pressure, diastolic blood pressure, LDH, AST and serum ALB) in patients with pre-eclampsia and FGR (Figure 4). The mRNA expression levels of SYDE1, HTRA1, PAPPA2, MYL9, OLFML3, VTN, and ANXA8 were significantly negatively correlated with fetal birth weight, systolic blood pressure, and diastolic blood pressure (p<0.01). Among the other clinical indicators, LDH levels showed the strongest correlation with OLFML3 expression, AST levels showed the strongest correlation with PAPPA2 expression, and OLFML3 and SYDE1 expression showed the strongest correlation with serum ALB levels (p<0.05).

Figure 4: The correlation heatmap of representative genes and clinical features of pre-eclampsia and fetal growth restriction. SBP, systolic blood pressure; DBP, diastolic blood pressure; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; ***p<0.001, **p<0.01, *p<0.05.
Figure 4:

The correlation heatmap of representative genes and clinical features of pre-eclampsia and fetal growth restriction. SBP, systolic blood pressure; DBP, diastolic blood pressure; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; ***p<0.001, **p<0.01, *p<0.05.

Discussion

The placenta serves as an important organ for the exchange of materials between the mother and fetus, bearing the crucial responsibility of providing ample nutrients and oxygen to the fetus [18]. Abnormal remodelling of the spiral artery in the placenta and placental hypoperfusion in early pregnancy are the primary etiological factors of pre-eclampsia and significant contributors to the development of FGR [19], 20]; however, the exact etiology of this condition remains unclear. In this study, we used RNA sequencing to identify differentially expressed genes (DEGs) in the placenta, and identified 208 key differentially expressed genes between pre-eclampsia and FGR and healthy controls. The present study showed that the G protein-coupled receptor signalling pathway, REDOX processes, and angiogenesis were strongly correlated with pre-eclampsia and FGR. KEGG enrichment analysis also revealed pathways involved in neuroactive ligand‒receptor interactions, complement and coagulation cascades, and the PI3K/Akt signalling pathway. Our RNA-seq results were consistent with those of previous studies [21], [22], [23], [24].

Our previous studies identified significant differences in the expression of SYDE1, HTRA1, PAPPA2, MYL9, OLFML3, VTN, AXNA8, ISLR, STAB1, and TPM2 via transcriptomic sequencing of preeclamptic and healthy placentas [17]. Similar disparities were noted in placentas of individuals with pre-eclampsia and FGR. This observation prompted us to hypothesize an association between these genes and the pathogenesis of pre-eclampsia and FGR. Subsequently, we validated these findings by qRT-PCR. Our results revealed that SYDE1, HTRA1, and PAPPA2 expression was significantly upregulated in pre-eclampsia and FGR, whereas MYL9, OLFML3, VTN, and AXNA8 expression was significantly downregulated (p<0.05), consistent with the RNA sequencing results. Elevated expression of PAPPA2 and HTRA1 in the placenta has been shown to inhibit trophoblast migration and invasion, resulting in insufficient transformation of spiral arteries and decreased oxygenation in the placenta, leading to the development of pre-eclampsia and FGR [25], 26]. Conversely, increased SYDE1 expression enhances trophoblast biological activity. The observed upregulation of SYDE1 in the placenta of pre-eclampsia and FGR may serve as an indication of a compensatory mechanism [27].

Within the cohort of genes with decreased expression, OLFML3 exhibited the most significant reduction in expression in the placenta of pre-eclampsia and FGR. OLFML3, a newly discovered secreted glycoprotein belonging to the OLF subfamily, is characterized by a conserved OFL domain located in its C-terminal region [28], 29]. Our previous study illustrated the protective function of OLFML3 expression in pre-eclampsia [17] and postulated that OLFML3 expression may also play a role in pre-eclampsia and FGR. However, further research is required to validate this hypothesis and establish a definitive link.

The prognoses of patients who present with pre-eclampsia and FGR exhibit notable heterogeneity and are closely associated with various clinical indicators including blood pressure, fetal birth weight, and serum biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin levels [12], 30]. Elevated blood pressure has been linked to an increased risk of heart failure, cerebrovascular accidents, and eclampsia and is a significant prognostic factor for disease severity [31]. Low birth weight is a significant independent predictor of various adverse complications such as bronchopulmonary dysplasia, intrapulmonary hemorrhage, neonatal sepsis, and necrotizing enterocolitis [32], [33], [34]. Serum ALT and AST levels serve as important biomarkers for liver injury, whereas low serum albumin levels, resulting from decreased albumin synthesis or excessive urinary protein loss, can lead to thoracoabdominal water retention and edema [11], 35]. Recognizing these unique yet interconnected clinical markers are crucial for the timely intervention and effective management of preeclampsia. Consequently, further analysis was conducted to assess the relationship between mRNA expression levels of representative genes and clinical characteristics. Our findings revealed that the mRNA expression levels of SYDE1, HTRA1 and PAPPA2 displayed a positive correlation with systolic and diastolic blood pressure, LDH and LST, while exhibiting a negative correlation with fetal weigh and serum albumin. And the mRNA expression levels of MYL9, OLFML3, VTN, and ANXA8 were significantly negatively correlated with systolic and diastolic blood pressure, LDH and LST, while exhibiting a positive correlation with fetal weight. These results suggest that these genes could serve as biomarkers for assessing the severity of pre-eclampsia and FGR, thereby offering novel insights for future diagnosis and treatment.

Our study had some limitations. First, the sample size is small. Second, placentas were obtained from patients with pre-eclampsia and FGR post-delivery. Therefore, it is difficult to determine whether the differentially expressed genes are the causative factors of pre-eclampsia, the results of pre-eclampsia, or merely a related phenomenon. Third, the changes in the placenta at the time of delivery and after delivery, before sampling, could possibly alter the findings of differential gene expression that may have occurred during the pregnancy.

Conclusions

In conclusion, despite notable progress in the field of molecular diagnostics, there remains a need for further endeavors aimed at devising approaches for the identification, prevention, and treatment of pre-eclampsia and FGR. In the present study, RNA sequencing was conducted to establish an initial profile of DEGs in the placentas of pre-eclampsia and FGR. Representative genes associated with clinical indicators have been identified in the placenta. Subsequent investigations will be conducted to comprehensively investigate these differentially expressed genes, with the aim of elucidating the underlying pathogenic mechanisms of pre-eclampsia and FGR, and to offer theoretical insights for early diagnosis and clinical management.

Corresponding authors: Yanjun Hu and Jianqiong Zheng, Department of Obstetrics and Gynecology, The Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People’s Hospital, Wenzhou Maternal and Child Health Care Hospital, No 57, CangHou Rd., Wenzhou, 325000, China, E-mail: (Y. Hu) (J. Zheng)
Yanjun Hu and Jianqiong Zheng contributed equally to this work.

Funding source: Fundamental Scientific Research Project of Wenzhou

Award Identifier / Grant number: Y2023018

Funding source: Natural Science Foundation of Zhejiang Province

Award Identifier / Grant number: LBY23H200008

Award Identifier / Grant number: LQ21H040007)

Funding source: Medical Health Science and Technology Project of Zhejiang Provincial

Award Identifier / Grant number: 2024KY1627

Acknowledgments

We appreciate the patients’ participation in this study.

  1. Research ethics: The study was approved by the Ethics Committee of the Wenzhou People’s Hospital (KY-2022-015).

  2. Informed consent: Written informed consent was obtained from each participant to ensure their voluntary participation and understanding of the study requirements.

  3. Author contributions: Haiying Chen: Data analysis and writing (original draft). Xiaoqing Li and Xiaoming Xu: data curation. Jianqiong Zheng and Yanjun Hu wrote the manuscript (reviewed and edited). All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpm-2025-0025).

Received: 2025-01-14
Accepted: 2025-03-26
Published Online: 2025-04-28
Published in Print: 2025-06-26

© 2025 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Pharmacologic thromboprophylaxis following cesarean delivery-what is the evidence? A critical reappraisal
  4. Fetal cardiac diagnostics in Indonesia: a study of screening and echocardiography
  5. Original Articles – Obstetrics
  6. Comparative analysis of antidiuretic effects of oxytocin and carbetocin in postpartum hemorrhage prophylaxis: a retrospective cohort study
  7. Severe thrombocytopenia in pregnancy: a cross-sectional analysis of perinatal and neonatal outcomes across different platelet count categories
  8. Association of urinary misfolded protein quantification with preeclampsia and adverse pregnancy outcomes: a retrospective case study
  9. Differentially expressed genes in the placentas with pre-eclampsia and fetal growth restriction using RNA sequencing and verification
  10. Upregulation of microRNA-3687 promotes gestational diabetes mellitus by inhibiting follistatin-like 3
  11. Placental elasticity in trisomy 21: prenatal assessment with shear-wave elastography
  12. Penicillin allergies and selection of intrapartum antibiotic prophylaxis against group B Streptococcus at a safety-net institution
  13. Assessing high-risk perinatal complications as risk factors for postpartum mood disorders
  14. Original Articles – Fetus
  15. Assessment of fetal thymus size in pregnancies of underweight women
  16. Normal fetal echocardiography ratios - a multicenter cross-sectional retrospective study
  17. Original Articles – Neonates
  18. Evaluation of the relationship of fetal lung elastography values with the development of postpartum respiratory distress in late preterm labor cases
  19. Short Communication
  20. Radiographic thoracic area in newborn infants with Down’s syndrome
  21. Letter to the Editor
  22. Teaching prospective parents basic newborn life support (BNLS) for unplanned out-of-hospital births
https://doi.org/10.1515/jpm-2025-0025
Schlagwörter für diesen Artikel
pre-eclampsia; placenta; fetal growth restriction; RNA sequencing
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Pharmacologic thromboprophylaxis following cesarean delivery-what is the evidence? A critical reappraisal
  4. Fetal cardiac diagnostics in Indonesia: a study of screening and echocardiography
  5. Original Articles – Obstetrics
  6. Comparative analysis of antidiuretic effects of oxytocin and carbetocin in postpartum hemorrhage prophylaxis: a retrospective cohort study
  7. Severe thrombocytopenia in pregnancy: a cross-sectional analysis of perinatal and neonatal outcomes across different platelet count categories
  8. Association of urinary misfolded protein quantification with preeclampsia and adverse pregnancy outcomes: a retrospective case study
  9. Differentially expressed genes in the placentas with pre-eclampsia and fetal growth restriction using RNA sequencing and verification
  10. Upregulation of microRNA-3687 promotes gestational diabetes mellitus by inhibiting follistatin-like 3
  11. Placental elasticity in trisomy 21: prenatal assessment with shear-wave elastography
  12. Penicillin allergies and selection of intrapartum antibiotic prophylaxis against group B Streptococcus at a safety-net institution
  13. Assessing high-risk perinatal complications as risk factors for postpartum mood disorders
  14. Original Articles – Fetus
  15. Assessment of fetal thymus size in pregnancies of underweight women
  16. Normal fetal echocardiography ratios - a multicenter cross-sectional retrospective study
  17. Original Articles – Neonates
  18. Evaluation of the relationship of fetal lung elastography values with the development of postpartum respiratory distress in late preterm labor cases
  19. Short Communication
  20. Radiographic thoracic area in newborn infants with Down’s syndrome
  21. Letter to the Editor
  22. Teaching prospective parents basic newborn life support (BNLS) for unplanned out-of-hospital births
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