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In vitro fertilization exacerbates stroke size and neurological disability in wildtype mice
N R Bonetti1, T A Meister2, R Soria2
1Center for Molecular Cardiology, University of Zurich, Switzerland; Department of Internal Medicine, Kantonsspital Baden, Baden, Switzerland.
International Journal of Cardiology
|August 26, 2021
Summary
Assisted reproductive technologies (ART) increase stroke severity and worsen outcomes in mice by causing premature vascular aging. These findings suggest ART may also increase stroke risk and severity in humans, necessitating early preventive measures.
Area of Science:
- Vascular Biology
- Neurology
- Reproductive Medicine
Background:
- Assisted reproductive technologies (ART) are linked to premature vascular aging in offspring.
- Vascular aging is a known risk factor for stroke and predicts poor stroke outcomes.
- The impact of ART on cerebrovascular complications in humans is unknown due to the population's young age.
Purpose of the Study:
- To investigate the effects of ART on stroke outcome in a mouse model.
- To determine if ART influences the severity and neurological deficits following ischemic brain injury.
- To explore potential mechanisms underlying ART-associated stroke outcomes.
Main Methods:
- Transient middle cerebral artery occlusion was used to induce ischemic/reperfusion brain injury in ART and control mice.
- Stroke volume and neurological performance (Bederson and RotaRod tests) were assessed.
- Plasma levels of TNF-alpha, blood-brain barrier permeability (IgG extravasation), tight junction protein expression (claudin-5, occludin), oxidative stress, and NO-bioactivity were analyzed.
Main Results:
- ART mice exhibited significantly larger stroke volumes (nearly 3-fold) compared to controls.
- Neurological performance was significantly worse in ART mice 24 and 48 hours post-stroke.
- ART mice showed increased plasma TNF-alpha, elevated blood-brain barrier permeability, decreased tight junction proteins, increased oxidative stress, and reduced NO-bioactivity.
Conclusions:
- ART predisposes to significantly worse morphological and functional stroke outcomes in mice.
- Altered blood-brain barrier permeability is a key mechanism contributing to adverse stroke outcomes in ART mice.
- ART-induced premature vascular aging is a likely risk factor for stroke occurrence and a mediator of adverse stroke outcomes.
