Theranostics 2021; 11(10):5028-5044. doi:10.7150/thno.56141 This issue

Research Paper

Distinct placental molecular processes associated with early-onset and late-onset preeclampsia

Zhonglu Ren1,2,3,4,5#, Yunfei Gao1#, Yue Gao1,2,3, Guanmei Liang1,2,3, Qian Chen1, Sijia Jiang1, Xiaoxue Yang1, Cuixia Fan1, Haizhen Wang1, Jing Wang1, Yi-Wu Shi6, Chaoqun Xiao1, Mei Zhong1, Xinping Yang1,2,3✉

1. Center for genetics and Developmental Systems Biology, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
2. Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence and Guangdong Key Laboratory of Psychiatric Disorders, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
3. Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
4. College of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
5. Medicinal Information & Real-World Engineering Technology Center of Universities in Guangdong Province, Guangzhou, 510006, China.
6. Institute of Neuroscience and Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Ren Z, Gao Y, Gao Y, Liang G, Chen Q, Jiang S, Yang X, Fan C, Wang H, Wang J, Shi YW, Xiao C, Zhong M, Yang X. Distinct placental molecular processes associated with early-onset and late-onset preeclampsia. Theranostics 2021; 11(10):5028-5044. doi:10.7150/thno.56141. Available from

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Graphic abstract

Background: Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Although several transcriptome studies have been done on placentae from PE patients, only a small number of differentially expressed genes have been identified due to very small sample sizes and no distinguishing of clinical subtypes.

Methods: We carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for dysregulated genes and the molecular network and pathways they are involved in.

Results: We identified two functionally distinct sets of dysregulated genes in the two major subtypes: 2,977 differentially expressed genes in early-onset severe preeclampsia, which are enriched with metabolism-related pathways, notably transporter functions; and 375 differentially expressed genes in late-onset severe preeclampsia, which are enriched with immune-related pathways. We also identified some key transcription factors, which may drive the widespread gene dysregulation in both early-onset and late-onset patients.

Conclusion: These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors. A few regulators may be the key drivers of the dysregulated molecular pathways.

Keywords: clinical subtypes, molecular mechanism, placenta, preeclampsia, transcriptome