Paternal Nicotine/Ethanol/Caffeine Mixed Exposure Induces Offspring Rat Dysplasia and Its Potential “GC-IGF1” Programming Mechanism
Abstract
:1. Introduction
2. Results
2.1. Meta-Analysis of the Population
2.2. PME Increases Paternal HPA Axis Activity and Impairs Testicular Function
2.3. Influences of PME on Pregnancy Outcomes and Offspring Development
2.4. Impairments of PME on HPA Axis Activity, Glucolipid Metabolism, and Sex Hormone Levels in Offspring
2.5. PME Induces Multiple Organ Dysfunction in Offspring
2.6. Paternal HPA Axis Activity Is Associated with Testicular Reproductive Function, Pregnancy Outcome, and Offspring Development
3. Discussion
3.1. Basis for PME Rat Model Establishment and Its Toxicological Significance
3.2. PME May Impair Paternal Reproductive Function by Activating the HPA Axis
3.3. PME Can Cause Fetal Multi-Organ Dysplasia with Obvious Organ Specificity and Sex Differences
3.4. “GC-IGF1” Axis Programming Alteration Might Be Involved in Fetal Multi-Organ Dysplasia by PME
3.5. Summary
4. Materials and Methods
4.1. Reagents
4.2. Meta Analysis
4.3. Animals and Treatments
4.4. Cell Culture, Treatment, and Flow Cytometry
4.5. Hematoxylin-Eosin (H&E) Staining
4.6. Immunohistochemistry and Immunofluorescence
4.7. Total RNA Extraction, Reverse Transcription, and RT-qPCR
4.8. Western Blotting
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Fetal Indicators | CON/PME | CON/PME |
---|---|---|
Male Serum Corticosterone | Female Serum Corticosterone | |
Body weight (g) | 0.726 **/0.946 ** | 0.737 **/0.926 ** |
Body length (cm) | 0.706 */0.836 * | 0.712 */0.802 * |
Serum IGF1 (ng/mL) | 0.819 */0.829 * | 0.737 **/0.818 ** |
Fetal Indicators | Paternal Serum Corticosterone ↑ | Paternal Sperm Motility ↓ | ||
---|---|---|---|---|
Male | Female | Male | Female | |
Body weight (g) | −0.543 * | −0.551 * | 0.831 ** | 0.519 * |
Body length (cm) | −0.639 ** | −0.375 | 0.616 ** | 0.324 |
Serum corticosterone (ng/mL) | −0.593 * | −0.757 * | 0. 715 ** | 0.575 ** |
Serum insulin growth factor 1 (ng/mL) | −0.602 * | −0.618 * | 0.543 * | 0.64 * |
Serum testosterone (ng/mL) | −0.649 ** | - | 0.417 ** | - |
Serum estrogen (ng/mL) | - | −0.352 | - | 0.14 |
Serum glucose (mmol/L) | −0.286 | −0.0001 | 0.457 | 0.119 |
Serum insulin (mmol/L) | −0.039 | −0.32 | 0.013 | 0.373 |
Serum triglyceride (mmol/L) | 0.023 | 0.197 | −0.273 | 0.34 |
Serum total cholesterol (mmol/L) | 0.061 | 0.454 | 0.107 | −0.435 |
Serum low-density lipoprotein cholesterol (mmol/L) | −0.29 | 0.423 | 0.45 | 0.002 |
Serum high-density lipoprotein cholesterol (mmol/L) | 0.073 | −0.224 | 0.349 | 0.373 |
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Liu, Y.; Zhang, C.; Liu, Y.; Zhu, J.; Qu, H.; Zhou, S.; Chen, M.; Xu, D.; Chen, L.; Wang, H. Paternal Nicotine/Ethanol/Caffeine Mixed Exposure Induces Offspring Rat Dysplasia and Its Potential “GC-IGF1” Programming Mechanism. Int. J. Mol. Sci. 2022, 23, 15081. https://doi.org/10.3390/ijms232315081
Liu Y, Zhang C, Liu Y, Zhu J, Qu H, Zhou S, Chen M, Xu D, Chen L, Wang H. Paternal Nicotine/Ethanol/Caffeine Mixed Exposure Induces Offspring Rat Dysplasia and Its Potential “GC-IGF1” Programming Mechanism. International Journal of Molecular Sciences. 2022; 23(23):15081. https://doi.org/10.3390/ijms232315081
Chicago/Turabian StyleLiu, Yi, Cong Zhang, Yi Liu, Jiayong Zhu, Hui Qu, Siqi Zhou, Ming Chen, Dan Xu, Liaobin Chen, and Hui Wang. 2022. "Paternal Nicotine/Ethanol/Caffeine Mixed Exposure Induces Offspring Rat Dysplasia and Its Potential “GC-IGF1” Programming Mechanism" International Journal of Molecular Sciences 23, no. 23: 15081. https://doi.org/10.3390/ijms232315081
APA StyleLiu, Y., Zhang, C., Liu, Y., Zhu, J., Qu, H., Zhou, S., Chen, M., Xu, D., Chen, L., & Wang, H. (2022). Paternal Nicotine/Ethanol/Caffeine Mixed Exposure Induces Offspring Rat Dysplasia and Its Potential “GC-IGF1” Programming Mechanism. International Journal of Molecular Sciences, 23(23), 15081. https://doi.org/10.3390/ijms232315081