Integrated Multi-Omics Reveals Disruption of Lipid-Steroid Regulatory Axis Underlying Chronic Heat Stress-Induced Ovarian Dysfunction in Mice.
5 affiliations
- 1College of Life Sciences, Sichuan Agricultural University, Xinkang Road 46, Ya'an 625014, China.
- 2College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
- 3Department of Clinical Sciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia.
- 4Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University (Chengdu Campus), Wenjiang, Chengdu 611130, China.
- 5Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia.
Abstract
Heat stress is an escalating environmental challenge that adversely affects mammalian reproductive physiology, yet the integrated molecular mechanisms through which ovarian tissue responds to sustained heat stress remain incompletely understood. This study investigated the effects of chronic heat stress on mouse ovarian tissue using an integrated multi-omics approach. Female C57BL/6 mice were exposed to heat stress at 42 °C for 20 min daily over 30 days. Whole ovarian tissues were subsequently analyzed using RNA sequencing, DIA-based proteomics, untargeted metabolomics, histological examination, and RT-qPCR validation. Histological analysis showed a significant reduction in secondary follicle profiles in heat-stressed mice, whereas primary and antral follicle profiles showed inter-animal variability and did not differ significantly between groups. Transcriptomic and proteomic analyses identified altered expression of lipid metabolism- and steroidogenesis-related molecules, including Apoa1, Apoa2, Lpl, Fads2, and Hsd17b2. Metabolomic profiling further showed marked changes in metabolites related to lipid metabolism and steroid hormone biosynthesis. Integrated pathway analysis revealed recurrent enrichment of pathways associated with lipid metabolism and endocrine regulation, particularly PPAR signaling, cholesterol metabolism, and steroid hormone biosynthesis. RT-qPCR validation confirmed altered expression of selected genes involved in lipid transport and steroidogenic pathways. These findings suggest that chronic heat stress may disrupt ovarian metabolic and endocrine homeostasis through alterations in lipid-steroid regulatory pathways. This study provides systems-level evidence supporting the involvement of interconnected metabolic pathways in heat stress-associated ovarian dysfunction.
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BibTeX
@article{nazir2026integrated,
title = {{Integrated Multi-Omics Reveals Disruption of Lipid-Steroid Regulatory Axis Underlying Chronic Heat Stress-Induced Ovarian Dysfunction in Mice.}},
author = {Farwa Nazir and Muhammad Ammar Baibrus and Muhammad Tariq and Mohamed Tharwat and Shiyuan Pei and Yang Wen and Jie Shen and Meilian Su and Qiuxia Liang and Guangbin Zhou and Fahad A Alshanbari and Guozhi Yu},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198671},
url = {https://europepmc.org/article/MED/42883915},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated Multi-Omics Reveals Disruption of Lipid-Steroid Regulatory Axis Underlying Chronic Heat Stress-Induced Ovarian Dysfunction in Mice.
AU - Farwa Nazir
AU - Muhammad Ammar Baibrus
AU - Muhammad Tariq
AU - Mohamed Tharwat
AU - Shiyuan Pei
AU - Yang Wen
AU - Jie Shen
AU - Meilian Su
AU - Qiuxia Liang
AU - Guangbin Zhou
AU - Fahad A Alshanbari
AU - Guozhi Yu
PY - 2026
DA - 2026/09/28
JO - International journal of molecular sciences
DO - 10.3390/ijms27198671
UR - https://europepmc.org/article/MED/42883915
AB - Heat stress is an escalating environmental challenge that adversely affects mammalian reproductive physiology, yet the integrated molecular mechanisms through which ovarian tissue responds to sustained heat stress remain incompletely understood. This study investigated the effects of chronic heat stress on mouse ovarian tissue using an integrated multi-omics approach. Female C57BL/6 mice were exposed to heat stress at 42 °C for 20 min daily over 30 days. Whole ovarian tissues were subsequently analyzed using RNA sequencing, DIA-based proteomics, untargeted metabolomics, histological examination, and RT-qPCR validation. Histological analysis showed a significant reduction in secondary follicle profiles in heat-stressed mice, whereas primary and antral follicle profiles showed inter-animal variability and did not differ significantly between groups. Transcriptomic and proteomic analyses identified altered expression of lipid metabolism- and steroidogenesis-related molecules, including Apoa1, Apoa2, Lpl, Fads2, and Hsd17b2. Metabolomic profiling further showed marked changes in metabolites related to lipid metabolism and steroid hormone biosynthesis. Integrated pathway analysis revealed recurrent enrichment of pathways associated with lipid metabolism and endocrine regulation, particularly PPAR signaling, cholesterol metabolism, and steroid hormone biosynthesis. RT-qPCR validation confirmed altered expression of selected genes involved in lipid transport and steroidogenic pathways. These findings suggest that chronic heat stress may disrupt ovarian metabolic and endocrine homeostasis through alterations in lipid-steroid regulatory pathways. This study provides systems-level evidence supporting the involvement of interconnected metabolic pathways in heat stress-associated ovarian dysfunction.
SN - 1422-0067
ER -