Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat

Abstract

In this study we examined the effects of exposure to the antiandrogenic fungicide vinclozolin (Vz) on the development of two sex-differentiated behaviors that are organized by the perinatal actions of androgens. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6, or 12 mg/kg Vz from the 14th day of gestation through postnatal day (PND)3. The social play behavior of juvenile offspring was examined on PND22 and again on PND34 during play sessions with a same-sex littermate. After they reached adulthood, the male offspring were examined with the ex copula penile reflex procedure to assess erectile function. Vz did not produce any gross maternal or neonatal toxicity, nor did it reduce the anogenital distance in male pups. We observed no effects of Vz on play behavior on PND22. However, the 12-mg/kg Vz dose significantly increased play behavior in the male offspring on PND34 compared with controls. The most dramatic increases were seen with the nape contact and pounce behavior components of play. The Vz effect was more pronounced in male than in female offspring. As adults, male offspring showed a significant reduction of erections at all dose levels during the ex copula penile reflex tests. The 12-mg/kg dose was also associated with an increase in seminal emissions. These effects demonstrate that perinatal Vz disrupts the development of androgen-mediated behavioral functions at exposure levels that do not produce obvious structural changes or weight reductions in androgen-sensitive reproductive organs.

Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide

“…Prenatal exposure of rats to vinclozolin affects play behavior, a sexually dimorphic trait. Hotchkiss et al (2003) reported a decrease in play behavior in rats following exposure to 200 mg vinclozolin/kg body weight/day on PND 2 and 3, whereas Colbert et al (2005) reported an increase following daily exposure to 12 mg vinclozolin/kg body weight/ day between GD 14 and PND 3. Erectile function was found to be significantly reduced in the latter study.…”

“…Indeed, exposure of Sprague-Dawley rats on PND 2 and 3 to 200 mg vinclozolin/kg reduced play behavior of male rats at PND 36-37 to a level characteristic of females; play behavior in rats is sexually dimorphic (Hotchkiss et al 2003). Strain, dose and age at exposure to vinclozolin might be important, because Long -Evans rats exposed daily to 12 mg vinclozolin/kg body weight/day from GD 14 to PND 3 had significantly increased play behavior on PND 34, and significantly reduced number of erections as adults (Colbert et al 2005).…”

Sexual Behavior: From Hormonal Regulation to Endocrine Disruption

“…Five of the 6 studies addressing the developmental effects of vinclozolin and phthalates at relatively high doses on components of sexual behavior in males reported behavioral changes [92-96]. Diminished erections and increased seminal emission were observed, together with reduced attractiveness, in rats exposed to vinclozolin [92, 96].…”

“…Diminished erections and increased seminal emission were observed, together with reduced attractiveness, in rats exposed to vinclozolin [92, 96]. Exposure to phthalates led to sexual inactivity [95], increases in the time to sexual behaviors and a decrease in the frequency of these behaviors in rats [93, 94].…”

Hormonal programming of rat social play behavior: Standardized techniques will aid synthesis and translation to human health

“…Rearing-the animal rears up on its hind legs Self grooming-any part of the body is cleaned Casto et al (2003) Pouncing-one animal lunges at another animal with its forepaws extended Wrestling-two animals tumble and roll over one another in a seeming attempt to gain a dominant position Boxing-both animals rear up on their hind legs and make jabbing movements at each other with their forepaws Pinning-the animal that is pinning stands over the opponent with its forepaws on the ventral surface of the opposing animal On-the-back-this is the reciprocal behavior of pinning, when an animal is in this position the entire ventral surface is exposed Colbert et al (2005) Nape attack-the snout of the target animal makes contact with the nape area of the partner animal Pounce-the target animal lunges forward with its forepaws extended and makes contact with the partner animal Pin-the target animal is positioned on top of the partner animal with its forepaws placed on the partner, the partner animal lies on its back, fully exposing its ventral surface to the target animal Wrestle-the target and partner animal roll and tumble with each other Mount-a component of the male copulatory pattern where the target animal approaches the partner animal from the rear, clasps its flanks, and mounts Dessi-Fulgheri et al (2002) Play-any activity involving exaggerated movements and inhibited attacks; it appears to achieve no obvious goal. Social behaviors-approaching (moving toward another), crawl-over (moving over another), crawl-under(moving under another), social investigation (sniffing another's body except anogenital area), anogenital sniffing, allogrooming (gentle grooming of another's fur), aggressive grooming (vigorous grooming of another), pouncing (bouncing over another), charging (rushing toward another with vigorous bouncing gait), chasing, riding (forepaws over the back of a moving partner), sideways posture (the animal orientates itself broadside on to another), aggressive posture (the animal orientates tiself at right angle to and over another), submissive posture (lying on the back with belly exposed to another), biting, withdrawing (all movements away from another), upright posture (with erect posture the rat exposes its belly to another), boxing (both rats stand up facing each other and boxing with forepaws), jumping (animal leaps vigorously into the air).…”