Gamete Cryopreservation: Molecular Mechanisms of Cellular Injury and Epigenomic Alterations in Human and Animal Models
- 1Department of Obstetrics and Gynecology, Medical Faculty, Cologne University, 50931 Cologne, Germany
- 2Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences (BAS), 1113 Sofia, Bulgaria
Abstract
In human spermatozoa, freezing and thawing are consistently associated with impaired membrane integrity, reduced motility, mitochondrial dysfunction, oxidative imbalance and alterations in DNA/chromatin stability. Regulated cell death pathways may additionally contribute to post-thaw deterioration; however, the strength of evidence differs among individual pathways, and emerging mechanisms such as ferroptosis remain less extensively characterized in human spermatozoa than conventional oxidative and apoptosis-associated injury. Evidence for cryopreservation-associated epigenomic alterations is similarly heterogeneous. Experimental and animal studies demonstrate changes in DNA methylation, histone modifications and non-coding RNA profiles. In contrast, human evidence is generally more reassuring and has not demonstrated consistent persistent abnormalities in major imprinting-associated methylation patterns. Accordingly, observations from animal models should not be directly extrapolated to human reproductive outcomes. By integrating human and experimental evidence while explicitly considering these differences in evidentiary strength, this review identifies established mechanisms, emerging molecular pathways and major unresolved questions in contemporary gamete cryobiology.
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BibTeX
@article{zhu2026gamete,
title = {{Gamete Cryopreservation: Molecular Mechanisms of Cellular Injury and Epigenomic Alterations in Human and Animal Models}},
author = {Xinxin Zhu and Plamen Todorov and Lora Gaydarova and Volodimir Isachenko},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219468},
url = {https://www.mdpi.com/1422-0067/27/21/9468},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gamete Cryopreservation: Molecular Mechanisms of Cellular Injury and Epigenomic Alterations in Human and Animal Models
AU - Xinxin Zhu
AU - Plamen Todorov
AU - Lora Gaydarova
AU - Volodimir Isachenko
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219468
UR - https://www.mdpi.com/1422-0067/27/21/9468
AB - In human spermatozoa, freezing and thawing are consistently associated with impaired membrane integrity, reduced motility, mitochondrial dysfunction, oxidative imbalance and alterations in DNA/chromatin stability. Regulated cell death pathways may additionally contribute to post-thaw deterioration; however, the strength of evidence differs among individual pathways, and emerging mechanisms such as ferroptosis remain less extensively characterized in human spermatozoa than conventional oxidative and apoptosis-associated injury. Evidence for cryopreservation-associated epigenomic alterations is similarly heterogeneous. Experimental and animal studies demonstrate changes in DNA methylation, histone modifications and non-coding RNA profiles. In contrast, human evidence is generally more reassuring and has not demonstrated consistent persistent abnormalities in major imprinting-associated methylation patterns. Accordingly, observations from animal models should not be directly extrapolated to human reproductive outcomes. By integrating human and experimental evidence while explicitly considering these differences in evidentiary strength, this review identifies established mechanisms, emerging molecular pathways and major unresolved questions in contemporary gamete cryobiology.
SN - 1422-0067
ER -