Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates
The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals.…
Recent studies in zebrafish and mouse models have unveiled a previously unknown mechanism by which paternal cardiac injury can elicit an inflammatory signal that travels to the gonads, subsequently impacting intergenerational cardiac health in vertebrates. The blood-gonadal barrier, which typically safeguards the germline from parental exposures, can be breached under exceptional circumstances, leading to consequences for the offspring.
Chronic stressors such as specific diets and traumatic experiences have been previously linked to intergenerational inheritance in mammals, but the effects of acute stress have remained largely unexplored.
Cardiac damage is known to alter peripheral organs, blood flow, metabolism, and the immune response, raising questions about its potential impact on the reproductive system. To investigate this, researchers employed zebrafish and mouse models to examine the intergenerational role of cardiac damage and repair.
In the first week following a cardiac cryolesion (a form of cardiac injury), male zebrafish gonads and gametes activated inflammatory responses. Notably, sperm chromatin accessibility was found to be altered in response to the cardiac injury. Offspring of cryoinjured zebrafish males exhibited changes in cardiac function and cardiac gene expression, indicating a ripple effect of the injury's impact across generations.
To further explore this phenomenon, researchers induced systemic sterile inflammation in the paternal generation, which mimicked the cardiac injury effects in the subsequent generation. Remarkably, anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features, suggesting a possible therapeutic avenue for mitigating the intergenerational effects.
Similar findings were observed in mouse testis after a neonatal injury, with these changes also manifesting in the hearts of their offspring. These results imply a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury across both zebrafish and mice, offering new insights into the potential inheritance of cardiovascular disease and opening up avenues for further research into this intriguing phenomenon.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
