Chronic Administration of 4-Tert-Octylphenol to Adult Male Rats Causes Shrinkage of the Testes and Male Accessory Sex Organs, Disrupts Spermatogenesis, and Increases the Incidence of Sperm Deformities1

Abstract

The environmental toxicant 4-tert-octylphenol (OP) has been shown to exert estrogenic effects on mammalian cells in culture. Recent findings from our laboratories demonstrate clearly that OP administration disrupts reproductive hormone secretion in the adult male rat, quite likely as a result of estrogenic action. In the present study, we investigated the impact of these or other OP-induced changes on male reproductive tissues. Adult male rats were injected with OP (20 or 80 mg) or estradiol valerate (EV; 0.8 or 8 microg) s.c. in oil three times a week for either 1 or 2 mo. We found that an 80-mg dosage of OP for 2 mo or an 8-microg dosage of EV for 1 or 2 mo greatly reduced sperm numbers and adversely influenced the sizes, weights, and histological structures of the testes, epididymides, ventral prostate glands, seminal vesicles, and coagulating glands. The 80-mg dosage of OP for 1 mo reduced epididymal tubule size to a lesser extent than after 2 mo of treatment. Otherwise, treatment with 80 mg OP for 1 mo, 20 mg OP for 1 or 2 mo, or 0.8 microg EV for 1 mo had little or no effect on the histology of the tissues we examined. Additional evaluation of sperm morphology revealed marked increases in the proportions of head and tail abnormalities from animals that had received 80 mg of OP or 8 microg of EV for 1 mo and 20 mg of OP for 2 mo. The head abnormalities consisted mainly of pin heads, detached heads, and the absence of hooks, while tail abnormalities included mainly broken, coiled, and bent tails. Our results clearly demonstrate that OP can severely reduce the size and/or function of all of the male gametogenic and accessory reproductive organs studied. Moreover, the similarity of these cell and tissue changes between rats treated with OP and those treated with EV further suggests that OP may exert its action in an estrogenic-like manner.

Differential Expression of 3.BETA.-Hydroxysteroid Dehydrogenase mRNA in Rat Testes Exposed to Endocrine Disruptors

“…NP is a weakly estrogenic compound generated from alkylphenol ethoxylates that is widely used in the production of plastics, textiles, and agricultural chemicals and in household applications and cosmetics [25,29,30]. Several studies have reported the adverse effects of NP on development of the male reproductive tract when animals are parentally exposed to NP [13,31]. Therefore, our results suggest that the inhibition of 3β-HSD mRNA production by NP and OP may be due to functional defects in Leydig cells such as a reduction in cytochrome P450 enzyme production.…”

“…Octylphenol (OP) exerts estrogenic action to suppress LH, FSH and testosterone secretion and enhance prolactin secretion. OP greatly reduces sperm number and adversely influences the size of the rat testis [13]. Diethylstilbestrol (DES) induces a reduction in testis formation and abnormal semen, resulting in infertility in rats [14,15].…”

Antiandrogenic and Estrogenic Compounds: Effect on Development and Function of Male Reproductive System

“…Importantly, all these effects were observed only when relatively high doses (400 mg/kg bw) of alkylphenols were used (Atanassova et al, 2000; Sharpe et al, 2003). Administration of high doses of alkylphenols to adult males resulted in reduced size and function of the testis, epididymis and male accessory glands, decreased serum LH, FSH and testosterone concentrations, increased apoptosis of germ cells and reduced sperm count (Blake & Boockfor, 1997;Boockfor & Blake, 1997;Han et al, 2004;Gong & Han, 2006;Kim et al, 2007). However, reports on the effects of lower doses (<200 mg/kg bw) of octylphenol on male reproductive system are contradictory (Bian et al, 2006;Kim et al, 2007).…”

Effects of Endocrine Disruptors (NP, DBP and BPA) on Sperm Characteristics and Development of IVF Embryos in Pig

“…BPA can mimic estradiol action in inducing vaginal coalification, uterine vascular permeability, growth and differentiation of the mammary gland and c-fos gene expression in the female reproductive tracts. NP and BPA can reduce function of male gametogenic and accessory reproductive organs, alter the release of pituitary and gonadal hormones, and disrupt sperm production in adult male rates (Boockfor and Blake, 1997;Howdeshell et al, 1999;Kwack et al, 2002).…”