Effects of sex hormones disruption, after prenatal and postnatal exposure to chlordimeform, on monoaminergic neurotransmitters systems in female and male rat’s prefrontal cortex

Zusammenfassung

Introduction: Chlordimeform, as well as other formamidine pesticides, has been described to induce permanent sex- and regiondependent effects on development of monoaminergic neurotransmitter systems. The mechanisms that induce these effects are not known, but it has been suggested that these effects could be related to monoamine oxidase (MAO) inhibition. However, chlordimeform is a very weak MAO inhibitor, which suggest that other mechanism should be involved. In this regard, formamidines, in general, and chlordimeform, in particular, alter the serum levels of steroid hormones, which regulate the expression of enzymes that mediate the synthesis and metabolism of monoaminergic neurotransmitters systems. Therefore, an alteration of these hormones in the brain could mediate the effects observed. Objectives and methods: In order to confirm that the formamidines produce permanent alterations of the monoamine neurotransmitter systems, through disruption of sex hormones in the brain, by alteration of the expression of the enzymes that synthesize and/or metabolize these neurotransmitters, we evaluated, in frontal cortex of male and female rats, the effect on the levels of testosterone and estradiol at 11 days of age, as well as the expression of MAO, COMT, BDH, TH, TRH, and AD enzymes at 60 days of age after maternal exposure to chlordimeform (5 mg/kg body weight). Results: Chlordimeform induced a significant decrease in testosterone and estradiol levels in frontal cortex of rats at 11 days of age. We observed sex interaction with treatment in the content of T and E2. We determined a bigger increase in the expression of TH [35,66% (P<0,001)] and TRH [42,14% (P<0,001)] enzymes in males than in females. Chlordimeform treatment did not alter the expression of MAO, COMT, AD, BDH enzymes, but decreased the expression of the enzymes TRH TH in both males and females. Conclusions: The present findings indicate that after maternal exposure to formamidines, in general, and chlordimeform, in particular, a permanent alteration of monoaminergic neurotransmitters, through alteration of the enzymes that synthetize these neurotransmitters, mediated by sex hormones disruption in frontal cortex is induced.