Paternal Fenitrothion Exposures in Rats Causes Sperm DNA Fragmentation in F0 and Histomorphometric Changes in Selected Organs of F1 Generation

The adverse effects of maternal pesticides exposure on the progeny is very well established. However, the impact of paternal exposure to pesticides such as Fenitrothion (FNT) on the histomorphometry of progeny’s organs in unexposed mothers are much less well studied. Therefore, this study aims to evaluate the effects of paternal FNT exposure on the sperm quality of the parent rat and its effects on the histomorphometry of the progeny’s organs. Randomly, male Sprague Dawley rats (n = 24) categorized as F0 were distributed equally into three groups namely Control, FNT-10, and FNT-20. Control received 1 mL/kg corn oil while FNT-10 and FNT-20 received 10 mg/kg and 20 mg/kg of FNT, respectively, via oral force feeding for 28 consecutive days. At the end of the study, male rats were mated with unexposed female rats and the male rats were sacrificed to obtain sperm for sperm characterization and DNA damage evaluation. Meanwhile, the rats’ progeny (F1) namely pControl, pFNT-10, and pFNT-20 were left to grow until postnatal day 70 before being sacrificed to obtain the matured organs for histology and morphometric analysis. Our results showed that both doses of FNT reduced sperm quality and caused DNA fragmentation in F0 rats compared with the control group (p < 0.05). The number of Leydig cells as well as the diameter of the seminiferous tubules and glomerulus of the pFNT-20 group had significantly decreased (p < 0.05) compared with the pControl group. The Bowman’s space of the pFNT-20 group had significantly increased (p < 0.05) compared with the pFNT-10 and pControl groups. Therefore, paternal exposure to FNT reduced the sperm quality and increased sperm DNA fragmentation in F0 male Sprague Dawley rats and altered the histology and morphometry of the selected organs in the F1 progeny.

Paternal Exposure to Cigarette Smoke alters Behavior and Gene and miRNA Expression in Offspring

Cigarette smoking causes neurobehavioral disorders such as anxiety, addiction, and attention-deficit hyperactivity disorder (ADHD). Smokers have higher rate (53%) of major depressive disorder than non-smokers (6%). Smokers absorb nearly 10% of nicotine from each cigarette (~10 –15 mg) and tar or CSC (cigarette smoke condensate; 5.3 mg of nicotine / ml). Exposure to nicotine in utero causes tremors and startle responses in newborns, and ADHD by age 6. However, studies that demonstrate paternal-mediated neurobehavioral changes in offspring are limited. We set out to determine whether paternal smoking alters neurobehavioral outcomes in offspring and underlying molecular mechanisms. Our male mouse model demonstrates that the CSC exposure in adult mice leads to altered emotionality, hyperactive and anxiety-like nature, reduced sensorimotor gating, and increased anxious depression in their F1 adolescents. This was preceded by dysregulation of neuronal receptors at protein and mRNA levels and their targeting miRNAs in fetal (e18.5) brain. These intergenerational molecular changes in F1 offspring seem to be mediated through CSC-altered miRNAs in F0 caudal sperm. In addition, the sub-chronic CSC treatment elevates miRNA levels in sire serum without hindering the postnatal growth of progeny. Thus, the paternal exposure to CSC causes behavioral and molecular changes in offspring possibly by altering the F0 sperm-borne miRNAs.