Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol.

Abstract

The induction of synthesis of the "female" yolk precursor protein vitellogenin (VTG) in male fish by estrogenic chemicals in the environment has been demonstrated in many recent reports. However, little is known about the organismal and biological significance of this phenomenon. To examine the relationship between VTG production in male fish and reproductive impairment, adult male medaka were exposed to 4-tert-octylphenol (OP), a known environmental estrogen, in concentrations ranging ftom 20 to 230 ppb for 21 days, under flow-through conditions. Following exposure, male fish were mated, in the absence of OP, with unexposed females.Breeding groups composed of exposed males and control females produced about 50% fewer eggs than control groups. VTG levels in serum of male fish increased with increasing OP exposure concentration and decreased after OP exposure was discontinued. Nevertheless, significant correlations (pO.0l) were observed between VTG levds in exposed male fish and 1) OP exposure concentrations, 2) percent of fertilized eggs, and 3) survival of embryos. OP-induced VTG synthesis and reproductive impairment appear to be closely linked phenomena. Histological exmination indicated spermatogenesis in OP-exposed fish was inhibited, and some exposed fish had oocytes in their testes. Finally, OP caused a significant increase in the number ofabnormally developing embryos, suggesting that .OP may be genotoxic as well as estrogenic. Environmental estrogens, or xenoestrogens, chemicals with bioactivity similar to the endogenous female hormone estrogen, are known to affect development and sexual maturation of (in)vertebrates. Xenoestrogens can exert their action by binding to the cell's estrogen receptor (ER), but they can also act through ER-independent mechanisms (5). Reported adverse effects in humans include increased incidences of breast cancer and reduced sperm counts, whereas wildlife populations affected by xenoestrogens display a variety of reproductive alterations such as cryptorchidism in the Florida panther, small baculum in young male otters, small penises in alligators, sex reversal in fish, and egg-shell thinning and altered social behavior in birds (3,4,6-8).Alkylphenol polyethoxylates (APEs) are nonionic surfactants widely used in the manufacturing of cleaning agents, plastics, paper, cosmetics, and food products (9). APEs are discharged from industrial wastewater as nontoxic, hydrophilic compounds. However, bacteria metabolize APEs into hydrophobic, estrogenic by-products, including p-nonylphenol and 4-tertoctylphenol (OP), that bioaccumulate in aquatic wildlife and may affect reproductive ability (10,11). These metabolites bind to the ER of fish and mammals (12)(13)(14), induce transcriptional activation of estrogen-responsive genes (15), and induce production of the yolk protein vitellogenin (VTG) in fish hepatocyte cell culture and in male rainbow trout (16)(17)(18)(19)(20). Of the alkylphenols examined, OP appears to be the most biologically active (9).VTG is normally synthesized in the liv...

In vitro profiling of endocrine disrupting effects of phenols

“…Some xenoestrogens showing both ER agonistic and antagonistic effects had been reported, which also were confirmed that the antagonistic activity of these compounds, although statistically significant, was biologically marginal (Soto et al, 1997). In an in vivo test, the vitellogenin was detected in serum of the male medaka fish exposed to 4-t-OP in all treatment group in steadily increasing concentrations (Gronen et al, 1999), proving the estrogenic activity of 4-t-OP in fish. Endocrine disrupters are widely known for their estrogenic and androgenic effects by binding to ER or AR.…”

Reproductive effects of prenatal exposure to nonylphenol on zebrafish (Danio rerio)

“…In the later life, these offspring may in turn suffer from impaired reproductive potential or lead to the failure in further reproduction. Among the various alterations in parents of fish during reproductive period, it has been suggested that induction of VTG in males, occurrence of intersex gonads and change of sexual behaviors were correlated with reproductive failure and proposed as biomarkers to indicate reproductive impairment (Jobling et al, 1998;Gronen et al, 1999;Cheek et al, 2001). However, in some other cases (Seki et al, 2002;Kang et al, 2002Kang et al, , 2003, induction of VTG and testis-ova does not necessarily predict reproductive impairment.…”

The phytochemical lindleyin, isolated from Rhei rhizoma, mediates hormonal effects through estrogen receptors

“…Vitellogenin is a yolk protein, which is scarcely present in male medaka, and is markedly induced by environmental estrogenic compounds (Gronen et al 1999, Shioda & Wakabayashi 2000. Exposure to 3 p.p.b.…”