The Transgenerational Transmission of the Paternal Type 2 Diabetes-Induced Subfertility Phenotype.

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.

Gestational arsenic exposure and paternal intergenerational epigenetic inheritance.

A growing body of evidence has shown that gestational exposure to environmental factors such as imbalanced diet, environmental chemicals, and stress can lead to late-onset health effects in offspring and that some of these effects are heritable by the next generation and subsequent generations. Furthermore, altered epigenetic modifications in DNA methylation, histone modifications and small RNAs in a single sperm genome have been shown to transmit disease phenotypes acquired from the environment to later generations. Recently, our group found that gestational exposure of F0 pregnant dams to an inorganic arsenic, sodium arsenite, increases the incidence of hepatic tumors in male F2 mice, and the effects are paternally transmitted to the F2. Here, we first overview the epigenetic changes involved in paternal intergenerational and transgenerational inheritance caused by exposure to environmental factors. Then, we discuss our recent studies regarding paternal inheritance of the tumor-augmenting effects in F2 mice by gestational arsenite exposure, in which we investigated alterations of DNA methylation status in F2 tumors and causative F1 sperm. We also discuss the possible targets of the F2 effects. Finally, we discuss future perspectives on the studies that are needed to fully understand the health effects of arsenic exposure.

Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring.

BACKGROUND: Heroin addiction is a growing concern, affecting the socioeconomic development of many countries. Little is known about transgenerational effects on phenotype changes due to heroin addiction. This study aims to investigate changes in level of anxiety and aggression up to four different generations of adult male rats due to paternal exposure to heroin. METHODS: Male Sprague-Dawley rats were exposed with heroin intraperitoneally (i.p.) twice-daily for 14 days with increasing dosage regimen (F0-heroin). Male Sprague-Dawley rats (6-weeks-old) were divided into: (1) heroin exposed group (F0-heroin) and (2) control group treated with saline solution (F0-control). The dosage regime started with the lowest dose of 3 mg/kg per day of heroin followed by 1.5 mg/kg increments per day to a final dose of 13.5 mg/kg per day. Offspring were weaned on postnatal day 21. The adult male offspring from each generation were then mated with female-naïve rats after 2 weeks of heroin absence. Open field test and elevated plus maze test were used to study the anxiety level, whereas resident intruder test was used to evaluate aggression level in the addicted male rats and their offspring. RESULTS: Heroin exposure in male rats had resulted in smaller sizes of the litters compared to the control. We observed a higher anxiety level in the F1 and F2 progenies sired by the heroin exposed rats (F0) as compared to the control rats. Paternal heroin exposure also caused significantly more aggressive offspring in F1 compared to the control. The same pattern was also observed in the F2. CONCLUSION: Our results demonstrated that the progenies of F1 and F2 sustained higher levels of anxiety and aggression which are due to paternal heroin exposure.