Maternal Isobutyl-Paraben Exposure decreases the Plasma Corticosterone Level in Dams and Sensitivity to Estrogen in Female Offspring Rats

Abstract

ABSTRACT. Isobutyl-paraben (IBP), a widely used preservative in a variety of foods, shows high comparative binding affinity to estrogen receptors. Here, we examined the effects of maternal exposure of rats to IBP on plasma hormone concentrations and organ weights in dams, ratio of male pups, anogenital distance, organ weights and plasma hormone concentrations in offspring, puberty, estrous cycle and response of organ weight and plasma hormone concentrations to estrogen in adult female offspring, and reproductive and adrenal function in adult male offspring, all of which are under developmental estrogen regulation, to clarify the estrogenic effects of IBP during gestation and lactation on the endocrine systems of dams and offspring. While maternal exposure of IBP decreased the plasma corticosterone concentration and increased the uterus weight in dams and increased uterine sensitivity to estrogen in adult female offspring, the other indices examined were largely unaffected by the present treatment. Even though these results indicate little sign of endocrine disrupting effects for IBP, the existence of activity may be a matter of concern due to the possible impact on the health of future generations.KEY WORDS: corticosterone, estrogen, isobutyl-paraben, maternal, rat.J. Vet. Med. Sci. 71(8): 1027-1033, 2009 Parabens have been the most widely used preservatives for more than 50 years in a variety of food, cosmetic and pharmaceutical products [2,4,23] due to their broad spectrum of activity, inertness, low cost and long history of safe use. They have been detected in human urine collected from a demographically diverse group of male and female adults with no known exposure to parabens, suggesting that the majority of people have already been exposed to them [32]. Several studies indicate that exposure to parabens modulates the endocrine system and thus may have harmful consequences on animal and human health [4,7,13,22,28] because of the estrogenic activities of these compounds in vitro and in vivo [7,24], and anti-estrogenic activity in human skin has been shown [22]. In addition, exposure to parabens during adult periods has been implicated in reduction of the male reproductive system in rodents [7,19,20,21], whereas a recent study could not confirm these effects [10]. On the other hand, investigation of the effects of exposure to parabens during gestation to lactation is important because exposure to estrogenic chemicals during development could be a contributory factor in the rising incidence of endocrine dysfunction of offspring later in life [3,5,14,16,26]. But, the effects of early exposure to parabens are not consistent in previous reports [6,13,27,28]. Furthermore, the effects of early exposure to parabens on the endocrine system in adult female offspring, except for vaginal opening and intact uterus weight [13], are unclear. Therefore, we examined the effects of maternal exposure to parabens on several aspects of the endocrine system in male and female offspring, especially the effects on plasma hormone co...

Maternal Exposure to Isobutyl-Paraben Impairs Social Recognition in Adult Female Rats

“…Previously, we showed that maternal exposure to IBP decreased uterine sensitivity to estrogen, which may be reflected in estrogen receptor (ER) expression in adult female offspring [19]. Similarly, previous works have shown that ER expression in animals treated with other estrogenic compounds is significantly lower than that in control animals [20,35].…”

“…The removal of, or an increase in, maternal glucocorticoids leads to similar consequences: immobility in the forced swim test and hypothalamic glucocorticoid receptor expression in adult offspring [38]. Impairment in social recognition behavior may reflect a decrease in plasma corticosterone concentration in IBP-exposed dams [19]; however, further studies are, necessary to confirm this.…”

“…In this study, to clarify whether early exposure to estrogenic chemicals predisposes to autistic behaviors, we analyzed the effect of maternal exposure to IBP on social recognition in adult offspring. In addition, we analyzed female offspring, because the major effect of maternal adrenalectomy on maladaptive behavior occurs in female offspring [38], and we previously reported that maternal IBP exposure decreased plasma corticosterone levels in dams [19]. Furthermore, IBP exposure may change estrogen susceptible systems, such as social recognition of female offspring, because we previously elucidated that maternal IBP exposure increased uterine sensitivity to estrogen in adult female offspring [19].…”

“…(Kaneka Medix Co., Osaka, Japan) that was either filled with IBP (Tokyo Chemical Industry Co., Ltd., Tokyo, Japan) or empty (control). We prevopisly showed that Silastic capsules filled with IBP release about 4.36 mg/l/ day IBP into 37°C saline [19]. At 7 weeks of age, female offspring were gonadectomized to remove the effects of inter-animal variability in circulating hormone levels.…”

“…IBP treatment has been shown to decrease plasma corticosterone levels in dams, suggesting that IBP may inhibit endogenous estrogen activities [19] that stimulate the HPA-axis [4,17]. Many studies have suggested that changes in maternal glucocorticoids levels may be in- volved in the manifestation of ASDs, because maternal stress associates with the prevalence rates of ASDs in humans [2,21,36].…”