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DNA Methylation Pattern of CALCA and CALCB in Extremely Premature Infants with Monochorionic Triplets after
Feng Gao1, Yujia Guo2, Xingting Chen2
1Department of Pathology, 1st Affiliated Hospital, Fujian Medical University, Fuzhou 350004, China.
Insights
Calcitonin gene-related peptide (CGRP) hypermethylation in umbilical cord tissues is linked to premature birth complications. This DNA methylation change may cause serious neonatal morbidities in very premature infants.
Area of Science:
- Neonatology
- Epigenetics
- Reproductive Medicine
Background:
- Premature infants face higher risks of neonatal diseases and death compared to full-term peers.
- DNA methylation variations are implicated in these pathological processes.
- Calcitonin gene-related peptide (CGRP) has diverse roles in pregnancy, including vascular adaptation and trophoblast cell function.
Purpose of the Study:
- To investigate the role of CGRP DNA methylation in the umbilical cord tissues of premature infants.
- To compare CGRP methylation levels and CGRP expression in premature neonates versus controls.
Main Methods:
- Utilized premature live births from single-chorionic triple embryo transfers as study subjects.
- Employed pyrosequencing to analyze CGRP promoter region CpG island methylation in umbilical cord DNA.
- Applied immunofluorescence to assess alpha-CGRP and beta-CGRP expression in umbilical cord blood vessel walls.
Main Results:
- Elevated CGRP methylation levels were observed in the umbilical cord tissues of very premature infants compared to database controls.
- Alpha-CGRP expression was reduced in the umbilical cord blood vessel walls of monozygotic triplets, particularly in fatal cases.
- Beta-CGRP exhibited a compensatory expression pattern in response to decreased alpha-CGRP.
Conclusions:
- CGRP hypermethylation in umbilical cord tissue is a significant finding in very premature infants.
- This epigenetic alteration may contribute to severe neonatal morbidities.
- CGRP dysregulation presents a potential target for understanding and managing complications in premature neonates.
Abstract:
Compared with full-term peers, premature infants are more likely to suffer from neonatal diseases and death. Variations in DNA methylation may affect these pathological processes. Calcitonin gene-related peptide (CGRP) plays a complex and diversified role in reproduction and chronic inflammation, and participates in the functional maintenance of vascular adaptation and trophoblast cells during pregnancy. Here, premature live births with single-chorionic triple embryos after single-embryo transfer were used as research objects, while full-term infants with double embryos and double-chorionic twins were used as controls. DNA was extracted from umbilical cord tissues for pyrosequencing to detect the methylation level of CpG island in CGRP promoter region. The average values of CGRP methylation in the umbilical cord tissues of very premature fetuses were higher than that of normal controls obtained from the databases. Immunofluorescence results showed that the expression of αCGRP was decreased in the blood vessel wall of the umbilical cord of monozygotic triplets, especially in death cases, while the βCGRP had a compensatory expression. In conclusion, our findings suggest that hypermethylation of CGRP might be considered as an important cause of serious neonatal morbidities.
