Developmental Differences in Myocardial Mitochondrial Reticulum Networks in the Offspring Exposed to Diabetic
Prathapan Ayyappan1,2, Tyler C T Gandy1, David Sturdevant1
1Sanford Research, Sioux Falls, SD 57104, USA.
Insights
Diabetic pregnancy impairs offspring heart development, leading to altered mitochondrial networks. This maldevelopment contributes to cardiovascular disease risk later in life.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Mitochondrial Biology
Background:
- Diabetic pregnancy elevates offspring risk for neonatal and adult cardiovascular disease (CVD).
- Previous studies indicated diabetic pregnancy impairs mitochondrial function in offspring hearts.
Purpose of the Study:
- To investigate the long-term impact of diabetic pregnancy on myocardial mitochondrial structure in offspring.
- To determine if early-life mitochondrial dysfunction influences adult heart structure and cardiometabolic risk.
Main Methods:
- Utilized a rat model of pregestational diabetes.
- Employed 3D serial block face-scanning electron microscopy (SBF-SEM) to analyze mitochondrial networks.
- Examined left ventricular sections from newborn, three-week-old, and four-month-old offspring.
Main Results:
- Diabetes-exposed offspring had significantly fewer perinuclear (PN) and intrafibrillar (IF) mitochondria at birth.
- Mitochondrial counts increased rapidly, showing no difference at three weeks but exceeding controls by four months.
- Despite increased counts, mitochondrial volumes remained significantly lower at all developmental stages.
Conclusions:
- Diabetic pregnancy induces maldevelopment of the myocardial mitochondrial reticulum in offspring.
- This structural abnormality likely contributes to the increased risk of adult cardiovascular disease.
Abstract:
Diabetic pregnancy increases the offspring's risk of neonatal and adult cardiovascular disease (CVD). We previously used a rat model (Sprague-Dawley) to show that diabetic pregnancy impairs mitochondrial bioenergetics, dynamics, mitophagy, and quality control in the offspring's heart, and we hypothesized that mitochondrial dysfunction during early development influences the adult myocardium structure to confer cardiometabolic disease risk with aging. Here, we used 3D serial block face-scanning electron microscopy (SBF-SEM) to analyze perinuclear (PN) and intrafibrillar (IF) mitochondrial networks in the left ventricular sections from control and pregestational diabetes-exposed newborn (NB) rats that were three-week-old and four-month-old. Diabetes-exposed myocardium had 50% fewer PN and 20% fewer IF mitochondria at birth but counts increased more rapidly, resulting in no difference at three weeks and 35% more PN and 49% more IF mitochondria by four months. Despite rising counts, mitochondria volumes remained significantly lower at every developmental timepoint. This shows that diabetic pregnancy causes maldevelopment of the myocardial mitochondrial reticulum which likely contributes to adult CVD.
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