Methylation Status of IGF-Axis Genes in the Placenta of South Indian Neonates with Appropriate and Small for Gestational Age

Abstract

Objective

Altered methylation patterns of insulin-like growth factor (IGF)-axis genes in small for gestational age (SGA) have been reported in different populations. In the present study, we analyzed the methylation status of IGF-axis genes in the placenta of appropriate for gestational age (AGA) and SGA neonates of South Indian women.

Methods

Placental samples were collected from AGA (n = 40) and SAG (n = 40) neonates. The methylation of IGF-axis genes promoter was analyzed using MS-PCR.

Results

IGF2, H19, IGF1, and IGFR1 genes promoter methylation was 2.5, 1.5, 5, and 7.5% lower in SGA compared to AGA, respectively. Co-methylation of IGF-axis genes promoter was 40% and 20% in AGA and SGA, respectively. IGF-axis gene promoter methylation significantly (p < 0.05) influenced the levels of IGFBP3 protein, birth weight, mitotic index, gestational weeks, and IGFR1 and IGFR2 gene expression.

Conclusion

IGF-axis genes methylation was lower in SGA than in AGA, and the methylation significantly influenced the IGF-axis components.

Keywords:

• IGF-axis
• methylation of genes
• placental tissue
• appropriate for gestational age
• small for gestational age

Acknowledgments

We acknowledge Ms. Manjula and Ms. Mala, nursing staff, Department of Obstetrics and Gynaecology, RLJH, Kolar, Karnataka, India, who helped to collect the samples. We also acknowledge Dr. Venkatachalam Perumal, Professor & Head, and Mr. Ravi Ramalingam, Ph.D scholar, Department of Human Genetics, for their support in designing methylation-specific primers and analyzing the quality and quantity of DNA samples at SRIHER (Deemed to be University), Porur, Chennai, India.

Author contributions

All authors contributed to the studys conception and design. Ms. Nithya M.N. and Dr. Venkateswarlu Raavi performed experiments, data collection, and analysis. Nithya M.N. wrote the first draft of the manuscript, and all authors commented on previous versions. All authors read and approved the final manuscript.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki and the guidelines of the Indian Council of Medical Research, Government of India. The Institution Ethics Committee of Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research (SDUAHER), Kolar, Karnataka, India, approved the study (Ref No: SDUMC/KLR/IEC/32/2019-20).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Disclosure statement

The authors declared that there are no conflicts of interest.

Additional information

Funding

The authors thank for the infrastructure and consumables support from Sri Devaraj Urs Academy of Higher Education and Research (Deemed to be university), Kolar 563 103, Karnataka, India.