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Maternal hypercholesterolemia during gestation is associated with elevated lipid levels of two-day-old neonates

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Abstract

Maternal hypercholesterolemia (MHC) during pregnancy is associated with the risk of developing aortic lesions in fetuses. There is also a possibility of faster progression of atherosclerosis in offspring born to hypercholesterolemic mothers (HCM) during their adulthood. We investigated whether elevated maternal cholesterol levels during pregnancy influence the lipid levels in offspring. We analyzed the lipid profile of mothers during the three trimesters, cord blood (CB) at birth, and neonatal blood (NB) on Day 2 postpartum in the offspring. Cholesterol levels of HCM significantly increased throughout gestation when compared to normocholesterolemic mothers (NCM). CB lipid levels of newborns of HCM were similar to the newborns of NCM. While NB of offspring of HCM had elevated levels of triglycerides (TG) (p < 0.01) and very low-density lipoprotein (VLDL) (p < 0.01) when compared to the offspring of NCM. MHC also resulted in low newborn birthweight (p < 0.05) and low placental efficiency (ratio of newborn birth weight to placental weight) (p < 0.01) but no change was observed in umbilical cord length or placental weight. Immunohistochemical analysis revealed no significant changes in the protein expression of genes involved in TG metabolisms such as LDLR, VLDLR, CETP, and PPARG. We report that MHC in mothers decreases placental efficiency and newborn birthweight while increasing lipid levels in neonates on the second postpartum day. Given that TG levels modulate the circulating Low-Density lipoproteins, the increase in these levels in neonates gains importance. Whether these consistently high levels cause atherosclerosis in early adulthood warrants further investigation.

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Data availability

All data generated or analyzed during this study are included in this article. Raw files and additional information may be available by the corresponding author upon reasonable request.

Abbreviations

MHC:

Maternal hypercholesterolemia

NC:

Normocholesterolemia

NCM:

Normocholesterolemic mother

HCM:

Hypercholesterolemic mother

TC:

Total cholesterol

LDL:

Low-density lipoprotein

HDL:

High-density lipoprotein

TG:

Triglyceride

VLDL:

Very low-density lipoprotein

CB:

Cord blood

NB:

Neonatal blood

BW:

Birth weight

PW:

Placental weight

LUC:

Length of umbilical cord

PE:

Placental efficiency

LDLR:

Low-density lipoprotein receptor

VLDLR:

Very low-density lipoprotein receptor

CETP:

Cholesteryl ester transfer protein

PPARG:

Peroxisome proliferator-activated receptor gamma

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Acknowledgements

We acknowledge the volunteers who participated in the study. We thank the nurses and staff of the labor room and neonatal intensive care unit (NICU) of Kerala Institute of Medical Sciences.

Funding

This work was supported by the Indian Council of Medical Research (ICMR), Ministry of Health, Government of India (File No. 5/4/1-5/2019-NCD-II). Jayalekshmi VS was funded by INSPIRE Ph.D. fellowship from the Department of Science and Technology, Government of India (IF170711).

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Authors and Affiliations

  1. Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, Kerala, India

    V. S. Jayalekshmi & R. S. Jagannath

  2. Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India

    V. S. Jayalekshmi

  3. Kerala Institute of Medical Sciences (KIMS), Thiruvananthapuram, Kerala, India

    S. Sreelekshmi, P. Rafeekha & R. Vidyalekshmy

  4. Medical Biotechnology, Gujarat Biotechnology University (GBU), Gandhinagar, Gujarat, India

    Surya Ramachandran

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  1. V. S. Jayalekshmi
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Contributions

JVS: performed the experiments, researched data, interpreted the data, and prepared the manuscript. JRS: collected and prepared the samples for analysis. SS: coded the recruits and curated the data. RP: recruited the subjects and provided the resources. VR: coordinated the study in KIMS hospital. SR: supervised the study, and reviewed and edited the manuscript.

Corresponding author

Correspondence to Surya Ramachandran.

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Conflict of interest

The authors declare no conflicts of interest. Authors also declare there are no financial interests exist.

Ethical approval

The study was approved by the Institutional Human Ethics Committee, Rajiv Gandhi Centre for Biotechnology (RGCB/IHEC/2019/10), and Institutional Human Ethics Committee, Kerala Institute of Medical Sciences (KIMS/IHEC/Hypercholesterolemia/NC/09/2019).

Consent to participate

Written informed consent was obtained from all recruited pregnant subjects for the study. Written informed consent was signed by the mothers for their neonates.

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Written informed consent to publish was individually obtained from all subjects. Consent to publish was obtained from the mothers of their neonates.

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Jayalekshmi, V.S., Jagannath, R.S., Sreelekshmi, S. et al. Maternal hypercholesterolemia during gestation is associated with elevated lipid levels of two-day-old neonates. Mol Cell Biochem 479, 363–371 (2024). https://doi.org/10.1007/s11010-023-04739-7

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