Maternal Hypoxia and Its Epigenetic Imprint: Long-Term Implications on Immune System Ontogeny and Forensic Biomarker Identification in Offspring

Authors

  • Augustine Chinedu Ihim Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria. https://orcid.org/0000-0001-9991-0714
  • Chinaza Favour Onyeje Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria.
  • Tochukwu Anthony Ikwelle Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria. https://orcid.org/0009-0007-0014-8637
  • Patrick Chinedu Obi Department of Internal Medicine, Federal University Teaching Hospital, Owerri, Nigeria https://orcid.org/0009-0009-7125-5602
  • Ini Edeh Medical Laboratory Science Council of Nigeria
  • Donatus F.N. Ozuruoke Department of medical laboratory science, Faculty of medical and health sciences, Newgate University, Minna. https://orcid.org/0000-0001-8798-7984
  • Romanus Ogai Ogalagu Department of Biochemistry, Faculty of Natural and Applied Sciences, Tansian University, Umunya, Anambra state. https://orcid.org/0000-0003-3460-5502

Abstract

Maternal hypoxia is a critical disruptor of fetal development, with enduring consequences for immune system ontogeny. This review examines the multifactorial impacts of intrauterine oxygen deprivation, emphasizing its role in impairing immune competence through disruptions in T and B cell differentiation, altered cytokine signaling, and long-lasting epigenetic reprogramming. The fetal immune system, highly sensitive to oxygen levels during gestation, is particularly vulnerable to these changes, which elevate lifelong susceptibility to infections, allergies, autoimmune diseases, and chronic inflammation. Hypoxia-inducible factors (HIFs) mediate many of these effects by interacting with epigenetic regulators such as DNA methylation, histone modifications, and non-coding RNAs that modulate gene expression without altering the DNA sequence. In addition to pathophysiological outcomes, the review highlights the forensic potential of hypoxia-induced epigenetic markers. These stable, exposure-sensitive modifications offer promising tools for reconstructing prenatal environments in post-mortem investigations, especially when traditional pathological indicators are absent. Technologies including bisulfite sequencing, pyrosequencing, and droplet digital PCR are evaluated for their utility in detecting these markers in degraded biological samples. This paper also addresses geographic and socioeconomic disparities that exacerbate hypoxia risks, particularly in high-altitude and low-resource settings, and underscores the importance of prenatal care, nutritional optimization, and early intervention. Based on a structured literature review of peer-reviewed studies from 2019 to 2024, this work integrates emerging evidence linking maternal hypoxia to immune dysfunction, developmental programming, and forensic science. It advocates for interdisciplinary research and public health strategies aimed at mitigating hypoxia-related risks and improving maternal-fetal outcomes across the lifespan.

Keywords: Maternal hypoxia, Forensic Biomarkers, Forensic Epigenetics, Immune dysfunction, Epigenetics Markers

Keywords:

immune response, Epigenetics, fetomaternal outcome

DOI

https://doi.org/10.22270/jddt.v15i11.7431

Author Biographies

Augustine Chinedu Ihim , Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria.

Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria.

Chinaza Favour Onyeje , Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria.

Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria.

Tochukwu Anthony Ikwelle , Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria.

Department of Clinical Chemistry, Faculty of Medical Laboratory Science Nnamdi Azikiwe University, Nnewi Campus, Awka, Nigeria.

Patrick Chinedu Obi , Department of Internal Medicine, Federal University Teaching Hospital, Owerri, Nigeria

Department of Internal Medicine, Federal University Teaching Hospital, Owerri, Nigeria

Ini Edeh , Medical Laboratory Science Council of Nigeria

Medical Laboratory Science Council of Nigeria

Donatus F.N. Ozuruoke , Department of medical laboratory science, Faculty of medical and health sciences, Newgate University, Minna.

Department of medical laboratory science, Faculty of medical and health sciences, Newgate University, Minna.

Romanus Ogai Ogalagu , Department of Biochemistry, Faculty of Natural and Applied Sciences, Tansian University, Umunya, Anambra state.

Department of Biochemistry,  Faculty of Natural and Applied Sciences,  Tansian University, Umunya, Anambra state.

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2025-11-15
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Ihim AC, Onyeje CF, Ikwelle T, Obi PC, Edeh I, Ozuruoke DF, et al. Maternal Hypoxia and Its Epigenetic Imprint: Long-Term Implications on Immune System Ontogeny and Forensic Biomarker Identification in Offspring. J. Drug Delivery Ther. [Internet]. 2025 Nov. 15 [cited 2026 Jan. 21];15(11):115-23. Available from: https://jddtonline.info/index.php/jddt/article/view/7431

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Vol. 15 No. 11 (2025): Volume 15, Issue 11, November 2025

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Review

Copyright (c) 2025 Augustine Chinedu Ihim , Chinaza Favour Onyeje , Tochukwu Anthony Ikwelle , Patrick Chinedu Obi , Ini Edeh , Donatus F.N. Ozuruoke , Romanus Ogai Ogalagu

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Ihim AC, Onyeje CF, Ikwelle T, Obi PC, Edeh I, Ozuruoke DF, et al. Maternal Hypoxia and Its Epigenetic Imprint: Long-Term Implications on Immune System Ontogeny and Forensic Biomarker Identification in Offspring. J. Drug Delivery Ther. [Internet]. 2025 Nov. 15 [cited 2026 Jan. 21];15(11):115-23. Available from: https://jddtonline.info/index.php/jddt/article/view/7431
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