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Disrupted placental vitamin D metabolism and calcium signaling in gestational diabetes and pre-eclampsia patients

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Abstract

Introduction

Gestational diabetes (GDM) and pre-eclampsia (PE) represents the unrecognized risk factors for reduced bone content in neonates. The present study is planned to explore the components of vitamin D metabolism and calcium transport in placenta of GDM and PE cases and its effect on the neonatal bone mass determination using bone densitometry system.

Methods

We have collected serum and placenta tissues from GDM (n = 20), PE (n = 20), and healthy pregnancies (n = 20). In the present study, we found mRNA expression of oxidative stress markers, vitamin D metabolic components and calcium channels, calcium channel binding proteins, plasma membrane calcium ATPase, ATP synthase and Ca2+ release genes; Ryanodine receptors genes were assessed by quantitative real-time PCR (qRT-PCR) in placental tissue of GDM, PE, and healthy pregnancies.

Results

We observed high level of oxidative stress in both GDM and PE placenta compared to normal pregnancies. CYP2R1 and VDR mRNA expression was significantly downregulated and upregulation of CYP27B1 and CYP24A1 in GDM and PE compared with healthy cases. Similarly, calcium transporters were downregulated in GDM and PE placental tissues. In addition, CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression were correlated with BMC of neonates.

Discussion

Oxidative stress is probably relevant to disrupted vitamin D homeostasis and calcium transport in the placenta of GDM and PE cases. The altered regulatory mechanism of CYP24A1 and VDR could indicates more pronounced serum 25(OH)D reduction. Additionally, reduced BMC in the neonates of these cases might be as consequences of modified CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression.

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Data availability

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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Acknowledgements

We acknowledge Ms. Tarang Gupta, Senior research fellow, Department of Endocrinology & Metabolism for her support in sample collection. S.V. is thankful to University Grant Commission (UGC) for providing postdoctoral fellowship for women (File No.F.15-1/2016-17/PDFWM-2015-17-UTT-37224 (SA-II)). S.V. also thanks full to Indian Society for Bone & Mineral Research (ISBMR) for providing financial support. R.Adela is thankful to Department of Science and Technology for providing the National Postdoctoral Research Fellowship (PDF/2016/000779).

Author contributions

S.V. and R.Adela contributed to study designing, sample collection, gene expression analysis, clinical data collection, data analysis, interpretation, and manuscript writing. G.K., V.K., and R.Kumari contributed to the study designing, interpretation, gynecological review. R.D. contributed to study designing, molecular data interpretation, and review. R.Agarwal contributed to the study designing, interpretation, and neonatal opinion. R.Khadgawat contributed to the study designing, interpretation, endocrine review. All authors critically revised the manuscript, agree to be fully accountable for ensuring the integrity and accuracy of the work, and read and approved the final manuscript.

Funding

S.V. is thankful to University Grant Commission (UGC) for providing postdoctroal fellowship for women (File No. F.15-1/2016-17/PDFWM-2015-17-UTT-37224 (SA-II)). R.Adela is thankful to Department of Science and Technology for providing National Postdoctoral Research Fellowship (PDF/2016/000779). S.V. received financial support from Indian Society for Bone and Mineral Research (ISBMR).

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Author notes

  1. These authors contributed equally: Shweta Varshney, Ramu Adela.

Authors and Affiliations

  1. Department of Endocrinology & Metabolism, All India Institute of Medical Science, New Delhi, India

    Shweta Varshney, Ramu Adela & Rajesh Khadgawat

  2. Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research−Guwahati, Guwahati, Assam, India

    Ramu Adela

  3. Department of Obstetrics & Gynecology, All India Institute of Medical Science, New Delhi, India

    Garima Kachhawa, Vidushi Kulshreshtha & Rajesh Kumari

  4. Department of Anatomy, All India Institute of Medical Science, New Delhi, India

    Reema Dada

  5. Department of Neonatology, All India Institute of Medical Science, New Delhi, India

    Ramesh Agarwal

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  1. Shweta Varshney
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Correspondence to Rajesh Khadgawat.

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Ethical approval

The study was reviewed and approved by the institutional ethics committee of the All India Institute of Medical Sciences-New Delhi (IEC/414/8/2016). The clinical study was conducted in accordance with principles outlined in the Declaration of Helsinki and institution and ethical standards. The individuals supplied written informed consent.

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Varshney, S., Adela, R., Kachhawa, G. et al. Disrupted placental vitamin D metabolism and calcium signaling in gestational diabetes and pre-eclampsia patients. Endocrine 80, 191–200 (2023). https://doi.org/10.1007/s12020-022-03272-9

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  • DOI: https://doi.org/10.1007/s12020-022-03272-9

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