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Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomised controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)

Published online by Cambridge University Press:  12 January 2023

Satyajeet P. Khare Open the ORCID record for Satyajeet P. Khare [Opens in a new window] ,
Ayush Madhok ,
Indumathi Patta ,
Krishna K. Sukla ,
Vipul V. Wagh ,
Pooja S. Kunte ,
Deepa Raut ,
Dattatray Bhat ,
Kalyanaraman Kumaran Open the ORCID record for Kalyanaraman Kumaran [Opens in a new window]  and
Caroline Fall
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Satyajeet P. Khare
Affiliation:
Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Lavale, Pune, India
Ayush Madhok
Affiliation:
Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India
Indumathi Patta
Affiliation:
Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India
Krishna K. Sukla
Affiliation:
Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India
Vipul V. Wagh
Affiliation:
Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Lavale, Pune, India
Pooja S. Kunte
Affiliation:
Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India
Deepa Raut
Affiliation:
Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India
Dattatray Bhat
Affiliation:
Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India
Kalyanaraman Kumaran
Affiliation:
Medical Research Council Lifecourse Epidemiology Centre, Southampton, UK
Caroline Fall
Affiliation:
Medical Research Council Lifecourse Epidemiology Centre, Southampton, UK
Utpal Tatu
Affiliation:
Indian Institute of Science (IISc), Bangalore, India
Giriraj R. Chandak
Affiliation:
Genomic Research on Complex Diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India
Chittaranjan S. Yajnik*
Affiliation:
Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India
Sanjeev Galande*
Affiliation:
Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar, Uttar Pradesh, India
*
Address for correspondence: Chittaranjan S. Yajnik, Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India. Email: csyajnik@gmail.com; Sanjeev Galande, Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India. Email: sanjeev@iiserpune.ac.in
Address for correspondence: Chittaranjan S. Yajnik, Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India. Email: csyajnik@gmail.com; Sanjeev Galande, Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India. Email: sanjeev@iiserpune.ac.in
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Abstract

In The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomised controlled trial ‘Pune Rural Intervention in Young Adolescents’. The interventions included: (1) vitamin B12+multi-micronutrients as per the United Nations International Multiple Micronutrient Antenatal Preparation, and proteins (B12+MMN), (2) vitamin B12 (B12 alone), and (3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-adenosyl methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow-up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.

Keywords

Vitamin B12 and micronutrientsrandomised controlled trialcord blood mononuclear cellsgene expression profilingcell cyclemitotic processes
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 3 , June 2023 , pp. 437 - 448
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Copyright
© The Author(s), 2023. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Footnotes

Satyajeet P. Khare and Ayush Madhok contributed equally.

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