Diethylstilbestrol induces fish oocyte maturation

Abstract

O ocyte maturation in lower vertebrates is triggered by maturation-inducing hormone (MIH), which acts on receptors located on the oocyte membrane and induces the activation of maturation-promoting factor in the oocyte cytoplasm (1-4). During the course of maturation, oocytes undergo drastic morphological changes associated with progression of the meiotic cell cycle, in which breakdown of the oocyte nuclear envelope [germinal vesicle breakdown (GVBD)] occurring at the prophase͞metaphase transition is usually regarded as a hallmark of the progress of oocyte maturation. Two MIHs, 17␣,20␤-dihydroxy-4-pregnen-3-one (17,20␤-DHP) and 17␣,20␤,21-trihydroxy-4-pregnen-3-one (20␤-S), have been identified in several fish species (5, 6). In goldfish, 17,20␤-DHP has been shown to induce oocyte maturation by stimulating the de novo synthesis of cyclin B, a regulatory subunit of maturationpromoting factor (7). Although progestins including 17,20␤-DHP and 20␤-S are the most potent steroid inducers of oocyte maturation in fish, other hormones such as deoxycorticosterone and testosterone, but not estradiol or its analogs, are also effective (8).Several endocrine-disrupting chemicals, Kepon and dichlorodiphenyldichloroethane, have been reported to antagonize MIH-induced meiotic maturation of fish oocytes in vitro (9). One of the environmental endocrine-disrupting chemicals (EEDCs), diethylstilbestrol (DES) is a nonsteroidal substance that was prescribed from the late 1940s to the early 1970s to pregnant women to prevent abortion, preeclampsia, and other complications of pregnancy. Male and female offspring exposed in utero to DES may develop multiple and neoplastic lesions of the reproductive tract, along with other changes, during development (10). Here we show that exposing fish oocytes to DES at a dose within a range similar to that used in experimental exposure to 17,20␤-DHP induces oocyte maturation. Estradiol-17␤ has been reported to be ineffective in inducing fish oocyte maturation (11, 12) and even inhibitory in several teleost species (13-15). Thus, the stimulatory effect of DES to induce fish oocyte maturation observed in this study has not been published previously. This report shows that EEDC can potentially induce oocyte maturation like an endogenous MIH, 17,20␤-DHP. Materials and MethodsMaterials. Goldfish were purchased from a local supplier and maintained at 15°C until used. Zebrafish were maintained at 28.5°C on a 14-h light͞10-h dark cycle (16). 17,20␤-DHP, DES, DES dimethyl ether (DM-DES), DES dipropionate (DP-DES), and 17␤-estradiol were purchased from Sigma. Dimethylstilbestrol (DMS) was a generous gift from J. Katzenellenbogen (University of Illinois, Urbana). 17␣-Estradiol, ethynylestradiol, butyl benzyl phthalate, di(2-ethylhexyl)-phthalate, and pentachlorophenol were obtained from Wako Pure Chemical (Osaka). Other chemicals were purchased as follows: hexestrol (HEX; ICN); trans,trans-dienestrol(␣-dienestrol) (DIES; U.S. Pharmacopeia, Rockville, MD); resveratorol (Calbiochem); DDTs (AccuStandard, New Haven, ...

Purification of the goldfish membrane progestin receptor α (mPRα) expressedin yeast Pichia pastoris

“…Membranes prepared from breast cancer cells transfected with mPRα exhibited single binding sites that were specific for a steroid that induced oocyte maturation in goldfish, 17,20β-DHP (38). We found that treatment of oocytes with diethylstilbestrol (DES), an endocrine disrupting chemical, induced their maturation in both goldfish and zebrafish (39). DES also bound with high affinity to membranes from mPRα-transfected breast cancer cells.…”

Estrogenicity of 4-nonylphenol and diethylstilbestrol on in vitro oocyte maturation of the dusky tripletooth goby,Tridentiger obscurus

“…Moreover, DES induced final maturation of goldfish and zebrafish oocytes in vitro, and it is suggested that DES has progestin-agonistic effects by binding ovarian membrane progestin receptor (Tokumoto et al 2004(Tokumoto et al , 2005(Tokumoto et al , 2007; the progestin-agonistic activity of DES was approximately 1% that of 17a20bOHP. In these studies, DES has progestinagonistic effects which are opposite to the other studies, in which DES has estrogen-agonistic effects, including our previous results.…”

“…In addition, the inhibition of progestin-induced GVBD by kepone and 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane (o, p'-DDD) has been demonstrated in oocytes of the Atlantic croaker, Micropogonias undulates (Ghosh and Thomas 1995). However, recent studies reported DES-induced oocyte maturation in vitro, and the authors suggested that DES can bind to progestin receptors, mimicking progestin (Tokumoto et al 2004;Baek et al 2007). …”

<b>Characterization of membrane progestin receptor α (mPRα) of the medaka and role in the induction of oocyte </b><b>maturation </b>

“…These results port that 17,20β-DHP is a MIH in these species. Previously, we have shown that oocyte maturation in zebrafish and goldfish can be induced by an endocrine disrupting chemical, diethylstilbestrol (DES) (19). In addition, we showed that DES binds to recombinant mPRα proteins expressed on the cell membranes of stably-transfected cultured cells, suggesting that DES induces oocyte maturation via interactions with mPRα and β (20,22).…”