Prenatal testosterone and luteinizing hormone levels in male rats exposed during pregnancy to 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol

Haavisto, Tapio; Nurmela, Katri; Pohjanvirta, Raimo; Huuskonen, Hannele; El-Gehani, Faraj; Paranko, Jorma

doi:10.1016/s0303-7207(01)00425-7

Cited by 58 publications

(49 citation statements)

References 70 publications

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“…These results suggest that DES administration altered pituitary function at 6 weeks of age, although it did not influence the pituitary at 3 weeks of age. Since it has been reported that administration of more than 100 times the dose of DES used in the present study to rats on days 13, 15 and 17 of gestation reduces the plasma testosterone level at 20 days of gestation, but does not change the LH content of the pituitary [2], further studies are necessary to investigate how the pituitary is involved in the postnatal decrease in testosterone after prenatal administration of DES.…”

Section: Discussionmentioning

confidence: 94%

“…It has been shown that the treatment of pregnant rats with DES dose-dependently (range: 10 to 300 μg/kg) suppresses testosterone levels in the blood and testes of male fetuses [2][3][4]. We administered doses of DES much lower (1.5 μg/kg) than those previously applied to pregnant rats at 7-21 days of gestation (in the second and third trimesters) and demonstrated that DES suppresses plasma testosterone levels in adolescent male offspring (6 weeks after birth) [5].…”

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confidence: 99%

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Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Kobayashi

Shirai

Sakaue

et al. 2009

Journal of Reproduction and Development

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Abstract.Our previous studies have demonstrated that prenatally administered diethylstilbestrol (DES) impairs testicular endocrine function in male offspring. The present study examined whether maternal DES treatment influences testicular steroidogenesis and spermatogenesis. DES was injected subcutaneously at 0.5 or 1.5 μg/kg/day (DES 0.5 and 1.5 groups, respectively) into pregnant SD rats on days 7-21 of gestation. Male offspring in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. At 1 week, DES treatment did not lead to a change in the volume of P450scc-positive cells (Leydig cells), suggesting that DES has no inhibitory effect on the development of Leydig cells. DES administration disrupted luteinizing hormone receptor (LHr) expression and exerted inhibitory effects on signal transduction from LHr to steroidogenic acute regulatory protein (StAR) in testicular steroidogenesis (P<0.05), although there were no changes in the mRNA expression levels of steroidogenic enzymes, such as P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD) and P45017α, which may have caused a decrease in the plasma testosterone level. DES treatment did not disrupt the cycle of spermatogenesis but did upregulate the expression levels of androgen receptor (AR) mRNA in both DES groups at 15 weeks (P<0.05). These results indicate that maternal DES treatment disrupts steroidogenesis but induces a high level of AR mRNA expression to counteract the low levels of testosterone during spermatogenesis. uring embryonic development, rat primordial germ cells appear in the yolk sac on embryonic day 10, and the gonadal primordium begins to develop as the genital ridge around embryonic day 11. Primordial germ cells begin to reach the genital ridge on embryonic day 12 [1]; thereafter, Sertoli and Leydig cells in the male differentiate from genital ridge cells, leading to a series of differentiation events. The duration of pregnancy is generally divided into periods of embryonic development (first trimester), organogenesis (second trimester) and organ maturation (third trimester).Diethylstilbestrol (DES), a synthetic non-steroidal estrogen, exhibits strong estrogenic activity by binding to estrogen receptors (ERs). It has been shown that the treatment of pregnant rats with DES dose-dependently (range: 10 to 300 μg/kg) suppresses testosterone levels in the blood and testes of male fetuses [2-4]. We administered doses of DES much lower (1.5 μg/kg) than those previously applied to pregnant rats at 7-21 days of gestation (in the second and third trimesters) and demonstrated that DES suppresses plasma testosterone levels in adolescent male offspring (6 weeks after birth) [5].Androgen plays an important role in the development and function of the testis and male reproductive tract via the androgen receptor (AR). Similarly, since ERs have been found in these tissues [6][7][8][9][10], estrogen may be involved in development of the male reproductive system. Nevertheless, it is apparent that male ER-or aromatase-knockout mice initially ...

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Kobayashi

Shirai

Sakaue

et al. 2009

Journal of Reproduction and Development

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“…Because testicular Leydig cells express estrogen receptors (ERs) (Fisher et al, 1997;Saunders et al, 1998), estrogens and estrogenic agents have adverse effects on Leydig cells, such as reduced testicular steroidogenesis (Haavisto et al, 2001;Houk et al, 2004), structural and functional abnormalities (Warita et al, 2006(Warita et al, , 2008Nakamura et al, 2010), and carcinogenic activities (Kurland et al, 1975;Reznik-Schüller, 1979;Deshmukh and Hartung, 1983;Fowler et al, 2000). Diethylstilbestrol (DES) is a synthetic compound with potent estrogenic activity and is generally believed to bind to ERs and mimic the action of the natural estrogen 17β-estradiol (E2).…”

Section: Introductionmentioning

confidence: 99%

Microarray and gene ontology analyses reveal downregulation of DNA repair and apoptotic pathways in diethylstilbestrol-exposed testicular Leydig cells

et al. 2012

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-This study investigated the deleterious effects of the synthetic non-steroidal estrogen diethylstilbestrol (DES) on testicular Leydig cells and compared these effects with those of the natural estrogen 17β-estradiol (E2). For that purpose, we performed microarray analysis of a mouse Leydig cell line (TTE1) treated with these estrogens, followed by Gene Ontology (GO) analysis and parametric analysis of gene set enrichment (PAGE). Most notably, GO analysis revealed a significant decrease in the biological processes of the GO categories "DNA repair" and "apoptotic program" in DES-exposed cells. PAGE showed that "cell death," which is a superior GO category including apoptosis in the GO tree structure, significantly decreased in DES-exposed cells but significantly increased in E2-exposed cells. Interestingly, only 2 genes (Tia1 and Gas1) with altered expression patterns in the "cell death" category were common between DES-and E2-treated cells. The downregulation of apoptotic cell death pathways and DNA repair capability of DES-exposed cells implies that DES promotes carcinogenic processes more strongly than E2 does. These findings suggest that molecular events that occur following DES and E2 treatments differ substantially in Leydig cells, and that the effects of synthetic estrogen and natural estrogen differ more substantially than previously suspected.

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“…3) In female rats, TCDD is known to result in endometriosis, 4) fewer pregnancies, 2) and teratogenicity 5) of offspring exposed via the maternal body. A decrease in plasma testosterone has been reported in many studies, 1,6) but no change 2,7,8) and even an increase 9) has been mentioned in some reports. The effects and outcomes vary widely according to TCDD dose, development status of the animals, exposure process, and animal strain.…”

Section: Introductionmentioning

confidence: 92%

Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Testosterone Production in Isolated Murine Testicular Cells.

Uchida

Yoshida

Inui

et al. 2002

JOURNAL OF HEALTH SCIENCE

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)is an endocrine disruptor that is known to have widespread effects on the reproductive system. We examined the effects of TCDD on testosterone production of primary cultured murine testicular cells. The cells, derived from the testes of ICR mice at age 65 days, were exposed to 10 -2 -10 4 pM TCDD for 3, 24, or 48 hr and treated with human chorionic gonadotropin for 6 hr to induce production of testosterone. At these concentrations of TCDD, the viability of testicular cells was not affected. No significant time-or TCDD concentration-dependent effects were observed on the secretion of testosterone. The data suggest that TCDD does not have a direct influence on testosterone production in the ICR mouse.

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Prenatal testosterone and luteinizing hormone levels in male rats exposed during pregnancy to 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol

Cited by 58 publications

References 70 publications

Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Microarray and gene ontology analyses reveal downregulation of DNA repair and apoptotic pathways in diethylstilbestrol-exposed testicular Leydig cells

Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Testosterone Production in Isolated Murine Testicular Cells.

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