Vaginal Adenosis in a Non-Diethylstilbestrol-Exposed 6-Year-Old Patient

Accetta, Solange Garcia; Rivoire, Waldemar Augusto; Monego, Heleusa Ione; Vettori, Daniela Vanessa; Freitas, Daniel Melecchi de Oliveira; Edelweiss, Maria Isabel Albano; Capp, Edison

doi:10.1159/000058063

Cited by 8 publications

(3 citation statements)

References 15 publications

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“…However, excessive exposure to estrogenic compounds could have deleterious consequences on foetal development. Indeed, clinical reviews of women who were exposed to the synthetic estrogen diethylstilbestrol showed that foetal exposure to high estrogenic compound had adverse developmental effects and could result in anomalies in adulthood [37-44]. Exposure in utero to environmental components with estrogenic activity could also results in reproductive disorders [45-47].…”

Section: Discussionmentioning

confidence: 99%

Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

Drolet

Simard

Plante

et al. 2007

Reprod Biol Endocrinol

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BackgroundDuring human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2.MethodsWe obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol) and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium.ResultsHigh 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium.ConclusionThe spatial and temporal expression of 17beta-HSD2 in the placenta during pregnancy and the comparison of 17beta-HSD2 expression and steroid levels between placental villi and endometrium are compatible with a role in the modulation of active and inactive forms of estrogens. Our observations strongly support the hypothesis that 17beta-HSD2 acts as a barrier decreasing estradiol secretion rates in the foetal circulation.

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Section: Discussionmentioning

confidence: 99%

Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

Drolet

Simard

Plante

et al. 2007

Reprod Biol Endocrinol

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“…In fact, the presence of glands in vaginae were described in women who were born before DES was clinically used, or after the administration of DES to pregnant women was stopped (Plaut, 1940; Sandberg et al, 1965; Sandberg, 1967; Blaikley et al, 1971; Ruffolo et al, 1971; Kurman and Scully, 1974; Robboy et al, 1986; Chattopadhyay et al, 2001; Paczos et al, 2010; Cebesoy et al, 2007; Accetta et al, 2001; Charlton et al, 2001). In utero exposure to other hormones or environmental chemicals may be the cause of non-DES associated adenosis in the cervix and vagina.…”

Section: Endocrine Disruptorsmentioning

confidence: 99%

The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero

et al. 2012

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Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well documented case in human history. DES, an orally active synthetic estrogen, was believed to prevent adverse pregnancy outcome and thus was routinely given to selected pregnant women from the 1940s to the 1960s. It has been estimated that 5 million pregnant women worldwide were prescribed with DES during this period. In the early 1970s, vaginal clear cell adenocarcinomas (CCACs) were diagnosed in daughters whose mother took DES during pregnancy (known as DES daughters). Follow up studies demonstrated that exposure to DES in utero causes a spectrum of congenital anomalies in female reproductive tracts and CCACs. Among those, cervical and vaginal adenoses are most commonly found, which are believed to be the precursors of CCACs. Transformation related protein 63 (TRP63/p63) marks the cell fate decision of Müllerian duct epithelium (MDE) to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression in mice and induces adenosis lesions in the cervix and vagina. This review describes mouse models can be used to study the development of DES-induced anomalies, focusing on cervical and vaginal adenoses, and discusses its molecular pathogenesis.

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“…There have been cases of cervical/vaginal adenoses/CCACs reported in women who have no history of DES exposure (Kurman and Scully, 1974; Robboy et al, 1986; Accetta et al, 2001; Herbst et al, 1975; Chattopadhyay et al, 2001). The persisting incidence of cervical/vaginal adenosis in the general population even after the ban of DES usage suggests the existence of other causal factors in our environment.…”

Section: Cervical/vaginal Adenosis and Ccac In Post-des Eramentioning

confidence: 99%

Normal and abnormal epithelial differentiation in the female reproductive tract

Kurita

2011

Differentiation

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In mammals, the female reproductive tract (FRT) develops from a pair of paramesonephric or Müllerian ducts (MDs), which arise from coelomic epithelial cells of mesodermal origin. During development, the MDs undergo a dynamic morphogenetic transformation from simple tubes consisting of homogeneous epithelium and surrounding mesenchyme into several distinct organs namely the oviduct, uterus, cervix and vagina. Following the formation of anatomically distinctive organs, the uniform MD epithelium (MDE) differentiates into diverse epithelial cell types with unique morphology and functions in each organ. Classic tissue recombination studies, in which the epithelium and mesenchyme isolated from the newborn mouse FRT were recombined, have established that the organ specific epithelial cell fate of MDE is dictated by the underlying mesenchyme. The tissue recombination studies have also demonstrated that there is a narrow developmental window for the epithelial cell fate determination in MD-derived organs. Accordingly, the developmental plasticity of epithelial cells is mostly lost in mature FRT. If the signaling that controls epithelial differentiation is disrupted at the critical developmental stage, the cell fate of MD-derived epithelial tissues will be permanently altered and can result in epithelial lesions in adult life. A disruption of signaling that maintains epithelial cell fate can also cause epithelial lesions in the FRT. In this review, the pathogenesis of cervical/vaginal adenoses and uterine squamous metaplasia is discussed as examples of such incidences.

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Vaginal Adenosis in a Non-Diethylstilbestrol-Exposed 6-Year-Old Patient

Cited by 8 publications

References 15 publications

Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero

Normal and abnormal epithelial differentiation in the female reproductive tract

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