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Oral pyrroloquinoline quinone (PQQ) during pregnancy increases cardiomyocyte endowment in spontaneous IUGR guinea pigs

Published online by Cambridge University Press:  02 March 2023

Jordan Mattern ,
Andrew Gemmell ,
Paige E. Allen ,
Katherine E. Mathers ,
Timothy R.H. Regnault Open the ORCID record for Timothy R.H. Regnault [Opens in a new window]  and
Brian K. Stansfield Open the ORCID record for Brian K. Stansfield [Opens in a new window]
Jordan Mattern
Affiliation:
Department of Pediatrics, Augusta University, Augusta, GA, USA
Andrew Gemmell
Affiliation:
Department of Pediatrics, Augusta University, Augusta, GA, USA
Paige E. Allen
Affiliation:
Departments of Physiology and Pharmacology, Western University, London, ON, Canada
Katherine E. Mathers
Affiliation:
Departments of Physiology and Pharmacology, Western University, London, ON, Canada
Timothy R.H. Regnault
Affiliation:
Departments of Physiology and Pharmacology, Western University, London, ON, Canada Department of Obstetrics and Gynecology Western University, London, ON, Canada Children’s Health Research Institute, London, ON, Canada
Brian K. Stansfield*
Affiliation:
Department of Pediatrics, Augusta University, Augusta, GA, USA
*
Address for correspondence: Brian K. Stansfield, MD, Division of Neonatology, Medical College of Georgia at Augusta University, 1446 Harper Street, Augusta, GA 30912, USA. Email: bstansfield@augusta.edu
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Abstract

Background:

Intrauterine growth restriction (IUGR) exerts a negative impact on developing cardiomyocytes and emerging evidence suggests activation of oxidative stress pathways plays a key role in this altered development. Here, we provided pregnant guinea pig sows with PQQ, an aromatic tricyclic o-quinone that functions as a redox cofactor antioxidant, during the last half of gestation as a potential antioxidant intervention for IUGR-associated cardiomyopathy.

Methods:

Pregnant guinea pig sows were randomly assigned to receive PQQ or placebo at mid gestation and fetuses were identified as spontaneous IUGR (spIUGR) or normal growth (NG) near term yielding four cohorts: NG ± PQQ and spIUGR ± PQQ. Cross sections of fetal left and right ventricles were prepared and cardiomyocyte number, collagen deposition, proliferation (Ki67) and apoptosis (TUNEL) were analyzed.

Results:

Cardiomyocyte endowment was reduced in spIUGR fetal hearts when compared to NG; however, PQQ exerted a positive effect on cardiomyocyte number in spIUGR hearts. Cardiomyocytes undergoing proliferation and apoptosis were more common in spIUGR ventricles when compared with NG animals, which was significantly reduced with PQQ supplementation. Similarly, collagen deposition was increased in spIUGR ventricles and was partially rescued in PQQ-treated spIUGR animals.

Conclusion:

The negative influence of spIUGR on cardiomyocyte number, apoptosis, and collagen deposition during parturition can be suppressed by antenatal administration of PQQ to pregnant sows. These data identify a novel therapeutic intervention for irreversible spIUGR-associated cardiomyopathy.

Keywords

IUGRheartfetusantioxidantPQQcardiomyopathy
Type
Brief Report
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 3 , June 2023 , pp. 321 - 324
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Copyright
© The Author(s), 2023. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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