Perinatal exposure to low levels of the environmental antiandrogen vinclozolin alters sex-differentiated social play and sexual behaviors in the rat

Environmental Health Perspectives, June, 2005 by Nathan K.W. Colbert, Nicole C. Pelletier, Joyce M. Cote, John B. Concannon, Nicole A. Jurdak, Sara B. Minott, Vincent P. Markowski

One of the questions examined in the present study was whether much lower levels of Vz during the perinatal period affect reproduction via a disruption of male copulatory behavior. An androgen-sensitive neuromuscular system that is critical for normal male copulatory behavior is the levator ani and bulbocavernosus (BC) skeletal muscles and their motor neuron control centers in the lumbar spinal cord [the spinal nucleus of the BC (SNB)]. In rats, contraction of the levator ani and BC muscles, as well as vascular mechanisms, produces penile erections (Hart and Melese-D'Hospital 1983; Leipheimer and Sachs 1993; Sachs 1982). The sex-specific development of the BC/SNB system is organized during the perinatal period by the non-aromatizable androgen dihydrotestosterone (DHT) (Hart 1979; Thomas et al. 1982). In developing males, the presence of DHT reduces motor neuron death in the SNB and promotes retention of the BC (Mills and Sengelaub 1993). In the adult male, there are two to three times more SNB motor neurons than in females (Sengelaub et al. 1989). However, environmental antiandrogen exposure can disrupt the development of the SNB/BC system. Vz exposure during the perinatal (Wolf et al. 2000, 2004) or peripubertal period (Monosson et al. 1999) significantly reduces the weight of the BC and levator ani muscles in adult males. Other antiandrogens such as procymidone, prochloraz, and linuron also affect the development of the BC muscle (Lambright et al. 2000; Ostby et al. 1999; Vinggaard et al. 2002).

What are the functional implications of an underweight BC muscle that has been affected by Vz exposure? Gray et al. (1994) have shown that adult male rats exposed to perinatal Vz will mount sexually receptive females but are unable to achieve vaginal penetration, suggesting that there is an underlying erectile dysfunction. Other environmental antiandrogens, such as p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), have already been shown to reduce erectile functions in rats (Brien et al. 2000). Female rats can detect subtle behavioral deficits and prefer to copulate with healthy, dominant males (McClintock et al. 1982). Antiandrogens could therefore affect the reproductive success of a wide range of animal species by altering male copulatory behavior. For instance, female guppies prefer males with high rates of sexual display, and Vz exposure has been shown to significantly reduce male guppy courtship display (Baatrup and Junge 2001; Bayley et al. 2002).

Most functional investigations of environmental endocrine disruptors have focused on the effects of perinatal exposure in adult offspring and have ignored the developmental trajectory of the effects of antiandrogen exposure. Juvenile play is a sexually dimorphic behavior that is an important precursor to adult sexual behavior (Pellis et al. 1992) and dominance relationships (Pellis and Pellis 1992). Males typically engage in more bouts of play and perform more behaviors during bouts than females (Thor and Holloway 1983). Even though they are prominent at different times in the life span, juvenile play and copulation are interconnected. During play, rats perform numerous crawl-over behaviors with same-sex partners. There is a shift of interest in male pups in their preferred play partners during the postnatal day (PND)36-40 period, from male to female (Meaney and Stewart 1981). Older, sexually mature but naive males will perform crawl-overs with females until they achieve a mount with a successful vaginal intromission. After the first intromission, mounting behavior increases and crawl-overs decrease. Adult males that do not have the opportunity to experience normal play during development show excessive play components but little normal copulatory behavior in the presence of sexually receptive females (Gerall et al. 1967; Goldfoot 1977; Gruendel and Arnold 1960; Hard and Larsson 1968). Thus, early environmental factors can affect important neonatal or juvenile social interactions, culminating in aberrant behaviors in adulthood (Dunlap et al. 1978).