5-AZA-2'-deoxycytidine (5-AZA-CdR): a demethylating agent affecting development and reproductive capacity

Area of Science:

• Developmental toxicology
• Reproductive toxicology
• Epigenetics

Background:

• 5-AZA-2 -deoxycytidine (5-AZA-CdR) is an epigenetic modifier.
• Its effects on postnatal development and reproductive capacity require thorough investigation.

Purpose of the Study:

• To evaluate the impact of in utero exposure to 5-AZA-CdR on the postnatal development and reproductive outcomes in mice.
• To assess the effects on body weight, mating behavior, fertility, and specific reproductive parameters in male offspring.

Main Methods:

• Pregnant mice received 5-AZA-CdR (1 mg/kg) on gestation day 10.
• Offspring (F1 generation) body weights were monitored.
• F1 males and females were mated with control mice to assess reproductive capacity.
• Male reproductive organs and sperm parameters were analyzed in F1 males.

Main Results:

• 5-AZA-CdR exposed offspring (F1) showed significantly reduced body weights compared to controls, with females more affected.
• Male reproductive capacity was adversely impacted, evidenced by lower pregnancy rates when F1 males mated with control females.
• Testicular and epididymis weights were reduced in F1 males, but higher relative to body weight. Sperm parameters were significantly lower, except for spermatid heads per mg of testis.

Conclusions:

• In utero exposure to 5-AZA-CdR induces developmental toxicity, leading to reduced postnatal growth and significant impairment of male reproductive function.
• The findings highlight the potential risks of epigenetic modifiers on offspring development and fertility.