The research is of importance as worldwide, especially in Europe, obstetricians and midwives are confronted with an escalation of obesity among pregnant women.
In the UK, where the prevalence of obesity in women is among the highest in Europe, around one in five women of reproductive age are now considered obese.
Evidence already suggests a child of an obese mother may suffer from exposure to a suboptimal in utero environment and that these early life adversities may extend into adulthood.
The study, conducted by a team from Washington University School of Medicine in the US city of St. Louis, found that prior to becoming pregnant, obese female mice with metabolic syndrome could pass on genetic abnormalities through the female bloodline to at least three generations,
These abnormalities include obesity-related conditions such as type 2 diabetes and heart disease.
“Our study indicates oocytes - or mothers' eggs - may carry information that programs mitochondrial dysfunction throughout the entire organism," said the study’s senior author Dr Kelle Moley, professor of Obstetrics and Gynecology at the university.
Mitochondria are cellular structures that have their own gene series. They are responsible for supplying energy for metabolism and other biochemical processes. Mitochondria are inherited only from mothers, not fathers.
In the study mice were fed a high-fat, high-sugar diet that consisted of approximately 60% fat and 20% sugar.
The next three generations of offspring, were all fed a control diet, which comprised of a diet high in protein and low in fat and sugar. Despite the healthy diet, offspring developed insulin resistance and other metabolic problems.
Additional investigations found the presence of abnormal mitochondria in muscle and skeletal tissue of the mice.
Research has already indicated that first generation offspring born to obese mothers are at an increased risk for being born large for gestational age.
This risk is also evident in developing obesity, cardiovascular disease and diabetes in adulthood.
The exact mechanism of action appears to centre on the degree of early life exposure to maternal obesity, which alters the cellular and physiological traits of the exposed offspring.
“Given that mitochondrial (mtDNA) is inherited from the mother, effects of maternal obesity on germline mitochondria must also be considered as a mechanism for transmission of metabolic dysfunction,” the authors commented.
The researchers also detected a decrease in activation of an enzyme (Drp1) in the offspring suggesting a reduction in mitochondrial fission.
Mitochondrial fission plays a critical role in maintaining functional mitochondria when cells experience metabolic or environmental stresses.
Fission is essential for targeting and degrading damaged mitochondria through mitophagy (the 'eating' of mitochondria). The process also contributes to quality control aiding in cell death (apoptosis) during high levels of cellular stress.
Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson’s.
Source: Cell Reports
Published online ahead of print, doi.org/10.1016/j.celrep.2016.05.065
“Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations.”
Authors: Kelle Moley et al.