Paternal Exposure to Methylphenidate Induces Poor-Quality Blastocyst and Epigenetic Changes

Area of Science:

• Reproductive biology
• Epigenetics
• Developmental toxicology

Background:

• Paternal epigenetic inheritance is an emerging area of research.
• Methylphenidate hydrochloride (MPH) is a widely prescribed psychostimulant.
• Previous studies suggested MPH's impact on paternal inheritance in fish.

Purpose of the Study:

• To investigate the effects of adolescent male rat exposure to MPH on blastocyst quality and epigenetic marks.
• To determine if MPH exposure impacts the epigenetic signature of mammalian blastocysts via paternal inheritance.

Main Methods:

• Male Wistar rats were administered MPH (5 mg/kg) or water daily from 38 to 68 days of age.
• Following treatment, rats were mated with untreated females.
• Blastocyst morphology and key epigenetic marks (H3K4me3, H3K9me3, H4K20me3) were assessed using immunocytochemistry.

Main Results:

• MPH treatment significantly reduced mean blastocyst quality by 43.57% (p=0.02).
• The proportion of "poor" quality blastocysts increased by over 150% (p<0.001).
• Epigenetic marks were altered, including increased H3K9me3 (p=0.01) and reduced H4K20me3 (p=0.05).

Conclusions:

• Subchronic MPH use by adolescent males is associated with a decline in blastocyst quality.
• This study provides the first evidence of MPH risks to the epigenetic signature of mammalian blastocysts following paternal exposure.
• MPH-induced epigenetic alterations may have implications for offspring health.