Fertility in Men Exposed Prenatally to Diethylstilbestrol (original) (raw)
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Endocrinology, 2002
The objective of the study was to determine the long-term effects of gestational and lactational exposure to diethylstilbestrol (DES; 0, 0.1, 1, and 10 g/kg maternal body weight) on mouse testicular growth, epididymal sperm count, in vitro fertilizing ability, and testicular gene expression using cDNA microarrays and real-time PCR in mice on postnatal day (PND) 21, 105, and 315. In the high dose group there was a persistent decrease in the number of Sertoli cells, and sperm count was decreased on PND315 (P < 0.05). Sperm motion was unaffected; however, the in vitro fertilizing ability of epididymal sperm was decreased in the high dose group on both PND105 (P < 0.001) and PND315 (P < 0.05). Early and latent alterations in the expression of genes involved in estrogen signaling (estrogen receptor ␣), steroidogenesis (steroidogenic factor 1, 17␣-hydroxylase/C17,20-lyase, P450 side chain cleavage, steroidogenic acute regulatory protein, and scavenger receptor class B1), lysosomal function (LGP85 and prosaposin), and regulation of testicular development (testicular receptor 2, inhibin/activin  C, and Hoxa10) were confirmed by real-time PCR. The results demonstrate that early exposure to DES causes long-term adverse effects on testicular development and sperm function, and these effects are associated with changes in testicular gene expression, even long after the cessation of DES exposure.
Lesions of testis and epididymis associated with prenatal diethylstilbestrol exposure
Environmental Health Perspectives, 1988
Cryptorchidism and retention of Mullerian duct structures occur with high frequency among the male offspring of CD-1 mice treated with 100 ,ug diethylstilbestrol/kg body weight on days 9 through 16 of pregnancy. Hyperplasia of the rete testis and Mfillerian duct structures were found in many of the DEStreated male mice, as was a low but significant number of reproductive tract neoplasms.
Reduced fertility in female mice exposed transplacentally to diethylstilbestrol (DES)
Fertility and Sterility, 1982
Prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, has been associated with a low incidence of vaginal adenocarcinoma as well as a variety of more numerous benign abnormalities in the reproductive tract of human beings and. experimental animals. For the purpose of assessing the effects of prenatal exposure to DES on postnatal reproductive tract function, timed pregnant CD~l mice were treated subcutaneously with doses of DES ranging from 0.01 to 100 jJ.{J/kg/day on days 9 through 16 of gestation. Thefertility of the female offspring was determined postnatally by a repetitive forced breeding technique. The most striking effect observed was a dose-related decrease in reproductive capacity ranging from minimal subfertility at the lower DES doses to a high frequency of total sterility at the highest DES doses. Reduced reproductive capacity appeared to be a reflection of both a decrease in the total number of litters and smaller litter sizes. A major component of the sterility seen in those females given higher doses of DES was oviductal/ovarian, since the number of ova recovered from the oviductal ampullae after induced ovulation was less than 30% that of controls. In addition, structural abnormalities of the oviduct, uterus, cervix, and vagina were observed, and contributed to infertility. These data suggest that in utero exposure to DES results in permanent impairment of female mouse reproductive capacity. Recent reports of altered pregnancy outcomes in young women who were exposed in utero to DES demonstrate the clinical importance of the findings obtained in mice.
Intrauterine exposure to diethylstilbestrol: Long-term effects in humans
APMIS, 2001
Swan SH. Intrauterine exposure to diethylstilbestrol: Long-term effects in humans. Review article. APMIS 2000;108:793-804. DES is the most carefully scrutinized EDC and its history provides valuable insights into the current evaluation of less well-studied EDCs. This review summarizes the health effects of prenatal exposure to diethylstilbestrol (DES) and emphasizes the role of DES as the first endocrine disrupting chemical (EDC). Vaginal clear cell adenocarcinoma (CCAC), the most severe consequence of prenatal exposure to DES, affected only 0.1% of exposed females, while the far more prevalent teratogenic and reproductive effects of DES were only discovered when DES daughter were screened for CCAC. Initial studies, conducted before most DES daughters had tried to conceive, examined vaginal cancer and vaginal, cervical and uterine abnormalities. Subsequently, several controlled studies demonstrated the increased risk of adverse reproductive outcomes in DES daughters. While most DES daughters can eventually experience a live birth, this is less likely in women with genital tract abnormalities, in whom there is a two-thirds chance that each pregnancy will be unsuccessful. In DES sons, who have been far less studied, results suggest male reproductive toxicity, but are less consistent. The importance of dose and gestational age at initial exposure are discussed, and the implications of DES findings for the evaluation of risks from current EDCs emphasized.
Testicular Tumors in Mice Exposed in Utero to Diethylstilbestrol
The Journal of Urology, 1987
Background: Early exposure to estrogen-like compounds has been implicated in the etiology of testicular cancer, but individual level epidemiologic data addressing this hypothesis are scarce. The synthetic estrogen diethylstilbestrol (DES) was administered during pregnancy from 1948 to 1971, but sequelae of in utero exposure have been more extensively characterized in females than in males. Methods: By systematic review, we sought to identify all epidemiologic research relating testicular cancer to a history of in utero exposure to diethylstilbestrol. Identified studies were critically appraised to assemble a set of nonredundant data in which any in utero exposure to DES was compared between men with incident testicular cancer and cancer-free men. These data were synthesized using random effects meta-analysis to estimate the summary association between in utero DES exposure and testicular cancer. Results: By meta-analysis of data from the six qualifying studies, the summary odds ratio estimate of the in utero DEStesticular cancer association was 2.98 (95% confidence interval ¼ 1.15 to 7.67). Conclusions: Results of this comprehensive meta-analysis accord with a threefold increase in testicular cancer risk among men who were exposed in utero to DES, implicating early hormonal exposures in etiology of testicular cancer. Because use of DES ceased in 1971, this work may provide the most comprehensive estimate of this association that will be made.
Lesions of the rete testis in mice exposed prenatally to diethylstilbestrol
Cancer research, 1985
Adenocarcinoma of the rete testis is an exceptionally rare and malignant testicular neoplasm. Although treatment of pregnant women with diethylstilbestrol (DES) results in reproductive tract abnormalities in their male offspring, increased incidence of testicular tumors has not been verified. However, recently three cases of seminoma have been described in men prenatally exposed to DES, suggesting an association of prenatal DES treatment and the subsequent development of testicular tumors. This report describes the treatment of outbred pregnant CD-1 mice with DES (100 micrograms/kg) on Days 9 through 16 of gestation and its effects on their male offspring. In addition to nonmalignant abnormalities such as retained testes which have been reported in men exposed prenatally to DES, lesions resembling adenocarcinoma of the rete testis were seen in prenatally DES-treated mice at 10 to 18 mo of age (11 of 233; 5%). No comparable lesions were seen in 96 age-matched control male mice. These...