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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Decreased ALCAM expression and promoter hypermethylation is associated with preeclampsia
Li-Li Wei1, Yue-Shuai Pan1, Qian Tang2
1Department of Nursing, The Affiliated Hospital of Qingdao University, Qingdao, China.
Insights
Preeclampsia is linked to lower expression of activated leukocyte cell adhesion molecule (ALCAM). Increased ALCAM gene promoter methylation in placental and blood samples suggests its role in preeclampsia development.
Area of Science:
- Obstetrics and Gynecology
- Epigenetics
- Molecular Biology
Background:
- Preeclampsia (PE) is a significant cause of maternal and fetal complications.
- Epigenetic alterations are implicated in PE pathogenesis.
- Activated leukocyte cell adhesion molecule (ALCAM) function in pathological pregnancy is unknown.
Purpose of the Study:
- To investigate ALCAM expression and methylation in PE patients.
- To explore the relationship between ALCAM methylation and PE.
- To determine ALCAM's role in PE pathogenesis.
Main Methods:
- Compared ALCAM mRNA and protein levels in placentas from PE and control groups.
- Assessed ALCAM promoter methylation rates in placental and peripheral blood samples.
- Examined the effect of demethylating agents on ALCAM expression in trophoblastic cells.
Main Results:
- ALCAM expression was significantly downregulated in PE placentas.
- Elevated ALCAM promoter methylation was observed in placentas and blood of PE patients.
- Demethylation treatment increased ALCAM transcription in trophoblastic cells.
Conclusions:
- ALCAM expression is reduced in preeclampsia.
- Increased ALCAM gene promoter methylation is associated with preeclampsia.
- ALCAM likely contributes to PE pathogenesis via epigenetic regulation.
Abstract:
Preeclampsia (PE) is a major obstetrical complication that results in maternal and fetal morbidity and mortality. Aberrant epigenetic modifications are widely involved in the pathogenesis of PE. Previously, the activated leukocyte cell adhesion molecule (ALCAM) was reported to be required for blastocyst implantation but has not been described in the context of pathological pregnancy. This study explored the expression of ALCAM and its methylation levels in the placentas and peripheral venous blood of patients with PE from a Chinese Han population. The mRNA and protein expression levels of ALCAM were downregulated in the PE placentas compared with the control placentas (P < 0.05). The methylation rate of the ALCAM gene promoter was considerably elevated in the placentas (P = 0.003, odds ratio (OR) = 0.264, 95% confidence interval (95% CI) [0.108-0.647], cases n = 47, controls n = 53) and peripheral blood (P = 0.007, OR = 0.455, 95% CI [0.256-0.806], cases n = 100, controls n = 100) of the PE patients compared with those of the normotensive women, suggesting a negative relationship between ALCAM methylation and gene transcription. Moreover, the transcriptional expression of ALCAM was dramatically increased by demethylating treatment in trophoblastic cells. ALCAM is expected to be involved in the pathogenesis of PE through methylation regulation.
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