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Published on: July 12, 2012
Variable Methylation Potential in Preterm Placenta: Implication for Epigenetic Programming of the Offspring
Vinita V Khot1, Preeti Chavan-Gautam1, Savita Mehendale2
11 Department of Nutritional Medicine, Interactive Research School for Health Affairs, Pune, Maharashtra, India.
Insights
Preterm birth is linked to later noncommunicable diseases. This study found lower methylation potential in preterm placentas, potentially impacting fetal epigenetic programming and future health.
Area of Science:
- Epigenetics
- Developmental Biology
- Nutritional Science
Background:
- Children born preterm face higher risks for adult noncommunicable diseases.
- Placental DNA methylation patterns are crucial for fetal programming of adult diseases.
- Micronutrients and long-chain polyunsaturated fatty acids (LCPUFAs) influence methylation via the 1-carbon cycle.
Purpose of the Study:
- To investigate the impact of preterm birth on placental methylation potential.
- To examine mRNA and protein levels of key enzymes (MAT2A, AHCY) in the S-adenosylmethionine pathway.
- To assess S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) levels, and global DNA methylation in preterm and term placentae.
Main Methods:
- Real-time quantitative polymerase chain reaction (qPCR) for mRNA analysis.
- Enzyme-linked immunosorbent assay (ELISA) for protein quantification.
- High-performance liquid chromatography (HPLC) for SAM and SAH level determination.
Main Results:
- Higher mRNA levels of MAT2A and AHCY were observed in preterm placentae.
- The SAM:SAH ratio was lower in the preterm group.
- Increased global DNA methylation was found in placentae of small for gestational age infants.
Conclusions:
- Preterm placentae exhibit altered enzyme expression and a reduced methylation potential.
- These epigenetic changes may contribute to the increased risk of noncommunicable diseases in individuals born preterm.
- Findings highlight the role of placental epigenetics in fetal programming and long-term health outcomes.
Abstract:
Children born preterm are reported to be at increased risk of developing noncommunicable diseases in later life. Altered placental DNA methylation patterns are implicated in fetal programming of adult diseases. Our earlier animal studies focus on micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids (LCPUFAs) that interact in the 1 carbon cycle, thereby influencing methylation reactions. Our previous studies in women delivering preterm show altered plasma levels of micronutrients and lower plasma LCPUFA levels. We postulate that alterations in the micronutrient metabolism may affect the regulation of enzymes, methionine adenosyltransferase ( MAT2A), and SAH-hydrolase ( AHCY), involved in the production of methyl donor S-adenosylmethionine (SAM), thereby influencing the methylation potential (MP) in the placenta of women delivering preterm. The present study, therefore, examines the mRNA, protein levels of enzymes ( MAT2A and AHCY), SAM, S-adenosylhomocysteine (SAH) levels, and global DNA methylation levels from preterm (n = 73) and term (n = 73) placentae. The enzyme messenger RNA (mRNA) levels were analyzed by real-time quantitative polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay, and SAM-SAH levels by high-performance liquid chromatography. The mRNA levels for MAT2A and AHCY are higher ( P < .05 for both) in the preterm group as compared to the term group. S-Adenosylmethionine and SAH levels were similar in both groups, although SAM:SAH ratio was lower ( P < .05) in the preterm group as compared to the term group. The global DNA methylation levels were higher ( P < .05) in women delivering small for gestation age infants as compared to women delivering appropriate for gestation age infants at term. Our data showing lower MP in the preterm placenta may have implications for the epigenetic programming of the developing fetus.
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