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Combined Maternal and Paternal Low‐Dose N‐Nitrosodimethylamine Exposure: Maternal Alterations and Developmental Toxicity in Rats

Year: 2025

Type: article

Abstract: BACKGROUND: N-Nitrosodimethylamine (NDMA) is an organic xenobiotic compound and a well-established mutagen and carcinogen. Its potential to cause reproductive and developmental toxicity at low, relevant doses is unclear. This study evaluated the effects of combined maternal and paternal NDMA exposure, both preconceptionally and during gestation, on maternal health and embryotoxicity in rats. METHODS: Rats were treated orally with vehicle (5 males, 10 females) or NDMA (7.2 ng/kg/day; 5 males, 12 females). Both sexes were exposed from postnatal day (PND) 60 to 90 (31 days); females continued during mating, and pregnant females from gestational day (GD) 0 to 20. On GD 20, dams were euthanized for hemato-biochemical and embryofetal evaluations. RESULTS: Clinical toxicity, fertility indices, and embryofetal parameters did not differ between groups. In NDMA-exposed dams, hematological analyses showed a significant reduction in lymphocyte percentages, an increase in monocyte counts, and a decrease in basophils, accompanied by elevated serum urea levels and reduced alanine aminotransferase (ALT) activity. Placental analyses were comparable between groups. Female fetuses exhibited a reduction in appropriate for gestational age (AGA) classifications with a concomitant increase in large for gestational age (LGA), while in males a borderline increase in placental efficiency was detected. No significant external, visceral, or encephalic malformations were observed. However, skeletal analysis revealed a significantly increased incidence of supernumerary ribs in NDMA-exposed fetuses. CONCLUSION: Combined maternal and paternal exposure to low-dose NDMA produced measurable adverse effects on maternal health and specific aspects of fetal development, highlighting its potential risk even at environmentally relevant exposure levels.

Source: Birth Defects Research