Effects of butyl paraben on the male reproductive system in mice

Abstract

Parabens are alkyl ester compounds of p-hydroxybenzoic acid widely used as preservatives in foodstuffs, cosmetics, toiletries and pharmaceuticals. These compounds are known to exert a weak estrogenic activity in estrogen receptor assays in vitro and in uterotrophic assays in vivo. In this paper, we have shown that butyl paraben had an adverse effect on the male mouse reproductive system and that it damaged the late steps of spermatogenesis in the testis. Butyl paraben was administered to 4-week-old Crj:CD-1 mice assigned to groups of eight animals, at doses of 0.01%, 0.10%, and 1.00% in the diet for 10 weeks. The average butyl paraben intake from the calculated food consumption was 14.4+/-3.60, 146+/-35.9, and 1504+/-357 mg/kg per day for the 0.01%, 0.10%, and 1.00% dietary butyl paraben groups, respectively. There were no treatment-related effects of butyl paraben on the liver, ventral prostates, seminal vesicles, and preputial glands (both in terms of absolute weight and relative to body weight) in any of the study groups. Both the absolute and relative weights of the epididymides were significantly higher in 1.00% group when compared with controls. A dose-dependent decrease of both round and elongated spermatid counts in stages VII-VIII seminiferous tubules was observed, and the elongated spermatid counts were significantly lower in all of the treated groups. The numbers of spermatogonia and spermatocytes did not differ from control values. The serum testosterone concentration decreased in a dose-dependent fashion and was significant at 1.00%. These data demonstrated that butyl paraben can exert an adverse effect on the male reproductive system at doses that are well below those of the accepted daily intake (ADI) in Japan.

Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products

“…The present data indicate that methyl-, propyl-and butyl-4-hydroxybenzoate are antiandrogens and some of these parabens can inhibit the T induced transcriptioanl activity by as much as 40% at a concentration of 10 μM. This observation provides a plausible and complementary explanation to the observed male reproductive disorders associated with these compounds (Oishi, 2002a;Oishi, 2002b) since the role of androgens in the development of the male reproduction tract, sexual accessory organs, spermatogenesis and maturation of spermatozoa is critical (Desjardins, 1978). It is, therefore, possible that some of these adverse effects are the result of lowered circulating androgen action by EDS which impedes androgen signaling.…”

“…Parabens have been shown to produce male reproductive disorders in animal models with a dose-dependent decrease of absolute and relative weights of epididymis, ventral prostates, as well as reduction in sperm reserve and daily production in rats (Oishi, 2002a;Oishi, 2002b). However, the underlying mechanism for these effects are largely unknown and has been speculated to be estrogen receptor mediated.…”

Environmental/lifestyle effects on spermatogenesis

“…Such products contain numerous chemicals, at least two of which (various types of parabens or phthalates) have been implicated in potentially causing adverse effects on testosterone and/or sperm production in animal studies (e.g. David et al 2000;Ishihara et al 2000;Oishi 2001Oishi , 2002, although for phthalates such effects have only been found after exposure to extremely high levels (500 -1500 mg kg 21 d…”

Androgenic and Antiandrogenic Effects of Alkylphenols and Parabens Assessed Using the Reporter Gene Assay with Stably Transfected CHO-K1 Cells (AR-EcoScreen System)

“…[20][21][22][23] Subsequently, it was reported that adverse effects occurred in the reproductive system of male rats and mice fed with food containing butyl-and propyl-parabens at a dose lower than or at the same level as the ADI. [24][25][26] The androgenicities of alkylphenols and parabens in in vitro assays have not been systematically reported. In this report, we examined the androgenic or antiandrogenic effects of some alkylphenols and parabens using the AR-EcoScreen system, and these results were compared with those using MDA-kb2 cells.…”