Does supplementation of oocytes with additional mtDNA influence developmental outcome?

Area of Science:

• Reproductive biology
• Developmental biology
• Genetics

Background:

• Extra mitochondrial DNA (mtDNA) supplementation in oocytes can rescue poor quality oocytes.
• However, this supplementation may alter DNA methylation and gene expression in preimplantation embryos.

Purpose of the Study:

• To investigate the long-term effects of autologous and heterologous mitochondrial DNA (mtDNA) supplementation on offspring health and development.
• To determine if mtDNA supplementation impacts DNA methylation and gene expression profiles.

Main Methods:

• Mitochondrial DNA (mtDNA) from autologous or heterologous sources was introduced into mature oocytes.
• Zygotes were transferred to surrogates, and offspring were monitored for growth, physiological parameters, and health.
• Analyses included mtDNA, imprinted genes, gross anatomy, morphology, and histopathology.

Main Results:

• Founders showed significantly greater daily weight gain and growth rates compared to controls.
• Weaners exhibited elevated cholesterol, bilirubin, anion gap, and lymphocyte counts.
• Mature pigs displayed altered potassium and bicarbonate levels. No aberrant mtDNA or imprinted gene profiles were found.

Conclusions:

• Mitochondrial DNA (mtDNA) supplementation induced minor physiological differences in offspring, including altered growth and biochemical profiles.
• No significant anatomical, morphological, or histopathological differences were observed.
• The observed minor differences did not affect the overall health and well-being of the offspring, and female founders were fertile.