Effects of Postnatal Administration of Diethylstilbestrol on Puberty and Thyroid Function in Male Rats

Abstract

Abstract.To examine the effects of diethylstilbestrol (DES) on male pubertal development and thyroid function, juvenile male Sprague-Dawley rats were given DES daily by oral intubation at doses of 10, 20 and 40 μg/kg/day from postnatal day 33 for 20 days. Prepuce separation was significantly delayed at the dose of 20 μg/kg/day and above in the DES-treated rats. DES treatment induced a significant reduction in the weights of testes, epididymides, the ventral prostate, seminal vesicles plus coagulating glands and fluid, levator ani bulbocavernosus muscles, Cowper's glands and the glans penis. The weights of the liver and adrenals increased in the DES-treated animals. DES caused a dosedependent reduction in germ cells; in particular the spermatids were mainly affected. The serum levels of testosterone and luteinizing hormone were significantly reduced in the DES-treated groups, but that of estradiol decreased. No differences were observed in the serum thyroxine levels of the control and DES-treated groups. In microscopic observation of the DES-treated animals, degeneration of germ cells and tubular atrophy in the testis were noted, but there were no microscopic changes in the thyroid. These results indicate that DES affected the pubertal development of juvenile male rats and that its mode of action may be related to alterations in hormone levels. Key words: Diethylstilbestrol, Male rat, Pubertal development (J. Reprod. Dev. 55: [461][462][463][464][465][466] 2009) oncerns have been raised about the potential adverse effects of environment chemicals that mimic the actions of estrogen on the reproduction and development of humans and wildlife species. Exposure of the developing male to exogenous estrogenic compounds can result in reproductive and developmental abnormalities and an increase in human male reproductive disorders, which include testicular cancer, cryptorchidism, hypospadias and low sperm counts [1][2][3][4]. Neonatal treatment with estrogens causes alterations in germ cell development and permanent impairment of testicular function [5][6][7][8][9]. As perinatal exposure of male animals and humans to synthetic estrogens can induce similar adverse changes in male reproductive health, it has been hypothesized that inappropriate exposure to estrogens during juvenile periods may interfere with the development of the reproductive system and with the sperm count in the adult [10,11]. Faced with growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influences of these substances on mammalian sexual differentiation and genital development [12,13].Diethylstilbestrol (DES) is a stilbene, a non-steroid estrogen, that can bind to estrogen receptors (ERs) and is widely used as a model estrogen for the study of estrogenic effects on the male reproductive function [13][14][15][16]. DES has been observed to have endocrine and reproductive toxicity in rats and mice. It is active over a wide dose range, showing effects on the mouse ventral prost...

Diethylstilbestrol decreased adrenal cholesterol and corticosterone in rats

“…Therefore, chronic corticosterone suppression induced by DES has the potential to disrupt the regulators of endocrine homeostasis and to facilitate the impairment of stress resistance. These findings constitute a new and important step towards understanding the mechanisms behind DES toxicity, such as reduced fertility, increased vaginal adenocarcinoma, and reduced testicular size and sperm count (Schrager & Potter 2004, Shin et al 2009, Unüvar & Büyükgebiz 2012. It is difficult to elucidate the mechanism of DES toxicity over the long term from the foetal stage to adulthood due to multiple hormone-related events such as foetal development, delivery and puberty.…”

Ept7 influences estrogen action in the pituitary gland and body weight of rats

“…Treatment of male rats with estrogens is known to decrease production of the gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH), which in turn reduces production of androgens by the testes, resulting in atrophy of the androgen dependent reproductive tissues (Shin et al 2009). In accord with this observation, micro-array data from our laboratory indicate the mRNAs encoding the beta subunits of both FSH and LH were dramatically reduced in response to DES treatment in both male ACI and male BN rats (manuscript in preparation; Tong et al 2012).…”

Effects of Bisphenol A and Diethylstilbestrol on Estrogen Receptor Expression and Male Fertility

“…Besides testosterone, decreased production of folliclestimulating hormone (FSH) and luteinizing hormone (LH) was also observed (Shin et al, 2009;Warita et al, 2006). Kobayashi et al (2009) conceded to the negative impact of steroidogenesis, but suggested that there was an increase in androgen receptor (AR) expression to compensate.…”