The Transgenerational Transmission of the Paternal Type 2 Diabetes-Induced Subfertility Phenotype
Eva Zatecka1, Romana Bohuslavova2, Eliska Valaskova1
1Laboratory of Reproductive Biology, Institute of Biotechnology Czech Academy of Sciences (CAS), Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec (BIOCEV), Vestec, Czechia.
Abstract:
Diabetes is a chronic metabolic disorder characterized by hyperglycemia and associated with many health complications due to the long-term damage and dysfunction of various organs. A consequential complication of diabetes in men is reproductive dysfunction, reduced fertility, and poor reproductive outcomes. However, the molecular mechanisms responsible for diabetic environment-induced sperm damage and overall decreased reproductive outcomes are not fully established. We evaluated the effects of type 2 diabetes exposure on the reproductive system and the reproductive outcomes of males and their male offspring, using a mouse model. We demonstrate that paternal exposure to type 2 diabetes mediates intergenerational and transgenerational effects on the reproductive health of the offspring, especially on sperm quality, and on metabolic characteristics. Given the transgenerational impairment of reproductive and metabolic parameters through two generations, these changes likely take the form of inherited epigenetic marks through the germline. Our results emphasize the importance of improving metabolic health not only in women of reproductive age, but also in potential fathers, in order to reduce the negative impacts of diabetes on subsequent generations.
Insights
Paternal type 2 diabetes negatively impacts male offspring reproductive health and metabolism across generations. These effects, including reduced sperm quality, are likely due to inherited epigenetic changes, highlighting the need for fathers to manage metabolic health.
Area of Science:
- Reproductive Biology
- Metabolic Disorders
- Epigenetics
Background:
- Diabetes mellitus is a chronic condition causing hyperglycemia and organ damage.
- Diabetic complications in men include reproductive dysfunction and reduced fertility.
- Molecular mechanisms of diabetes-induced sperm damage and reproductive issues are not fully understood.
Purpose of the Study:
- To investigate the effects of paternal type 2 diabetes on male reproductive health and outcomes.
- To evaluate intergenerational and transgenerational impacts on male offspring.
- To explore potential epigenetic mechanisms underlying these effects.
Main Methods:
- Utilized a mouse model to study type 2 diabetes exposure.
- Assessed reproductive parameters and metabolic characteristics in fathers and male offspring.
- Investigated potential inherited epigenetic alterations in the germline.
Main Results:
- Paternal type 2 diabetes exposure led to impaired sperm quality in male offspring.
- Metabolic characteristics were also negatively affected across generations.
- Evidence suggests transgenerational effects mediated by inherited epigenetic marks.
Conclusions:
- Paternal diabetes can induce lasting reproductive and metabolic deficits in offspring through two generations.
- Epigenetic modifications in the germline likely play a crucial role.
- Improving metabolic health in potential fathers is vital to prevent adverse effects on subsequent generations.
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