Paternal exposure to low-dose N-nitrosodimethylamine (NDMA) induces intergenerational alterations in the prostatic microenvironment of rats.

NDMA is a nitrosamine recognized as an environmental contaminant of water and food, unintentionally formed during industrial processes and water treatment. Due to its mobility in aquatic environments, persistence, and carcinogenic potential, NDMA has emerged as a toxicological and public health concern. This study evaluated the effects of low-dose exposure (7.2 ng/kg/day) on the prostate of male Wistar rats across two generations within the Paternal Origins of Health and Disease (POHaD) framework. F0 males were exposed via gavage from postnatal day (PND) 60 to 104. In F1, offspring were evaluated at PND70 (paternal exposure) and PND120 (direct exposure PND22-70). Exposed F0 males showed increased prostate weight. Stereology revealed epithelial expansion and luminal reduction in F0 and F1 (PND120), increased interstitial area in paternally exposed offspring, and reduced interstitium in F1 (PND70). Collagen analyses showed reduced type III in F0 and reduced types I and III in F1 (PND70), while type I increased in F1 (PND120) with exposure. All groups exhibited inflammatory infiltrate and mast cell degranulation. RT-qPCR indicated decreased androgen receptor (Ar) expression in F1 (PND120) with exposure, reduced Tnf-α in exposed F1, and increased Il-6 only in exposure. NDMA induced direct and intergenerational prostatic toxicity, reinforcing the POHaD concept.