Effects of diethylstilbestrol on ovarian follicle development in neonatal mice

Kim, Hannah; Hayashi, Shinji; Chambon, Pierre; Watanabe, Hidenobu; Iguchi, Taisen; Satō, Tomomi

doi:10.1016/j.reprotox.2008.10.005

Cited by 33 publications

(21 citation statements)

References 53 publications

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“…The daughters of women given DES while pregnant were early shown to have rare cervicovaginal cancers (Barclay, 1979;Herbst et al, 1971), decreased fertility and an increased rate of ectopic pregnancies (Goldberg and Falcone, 1999), and early menopause (Hatch et al, 2006). Later, experimental studies on animal models exposed to DES during gestation supported these antecedents (Kim et al, 2009;Miyagawa et al, 2011;Newbold, 2008;Newbold et al, 2007). In accordance with these observations, we found that the female rats neonatally exposed to a low dose of DES exhibited uterine functional abnormalities that compromised fertility.…”

Section: Discussionsupporting

confidence: 77%

Neonatal exposure to low doses of endosulfan induces implantation failure and disrupts uterine functional differentiation at the pre-implantation period in rats

Milesi

Alarcón

Ramos

et al. 2015

Molecular and Cellular Endocrinology

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Section: Discussionsupporting

confidence: 77%

Neonatal exposure to low doses of endosulfan induces implantation failure and disrupts uterine functional differentiation at the pre-implantation period in rats

Milesi

Alarcón

Ramos

et al. 2015

Molecular and Cellular Endocrinology

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“…Gdf9 has three newborn ovary homeobox gene (Nobox)-binding elements in the promoter region and is directly regulated by NOBOX, which is expressed in primordial and growing oocytes [45,52,53]. Expression of Nobox mRNA was not changed by DES treatment [54]; therefore, the NOBOX-GDF9 cascade is not affected by DES.…”

Section: Discussionmentioning

confidence: 99%

Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries1

Kim

Nakajima

Hayashi

et al. 2009

Biology of Reproduction

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In mice, neonatal exposure to a synthetic estrogen, diethylstilbestrol (DES), induces polyovular follicles, which contain two or more oocytes per ovarian follicle. We reported previously that the estrogen receptor beta (ESR2) mediates DES signaling in polyovular follicle induction. However, the specific mechanism of polyovular follicle induction has not yet been clarified. Folliculogenesis in rodents begins soon after birth, accompanied by programmed oocyte death and germ cell loss. In this study, the effects of DES on oocyte death and on mRNA expression of genes thought to be involved in polyovular follicle induction were analyzed during a crucial period of folliculogenesis in the ovary of C57BL/6J, Fas(lpr/lpr) (lacking cell death receptor, FAS), and Esr2 knockout (Esr2 KO) mice. Neonatal DES exposure reduced programmed oocyte death in C57BL/6J mice; however, this reduction was not observed in Esr2 KO mice. In control Fas(lpr/lpr) mice, the oocyte apoptotic index was significantly lower than that in the control C57BL/6J mice. However, the polyovular follicle incidence in control 20-day-old Fas(lpr/lpr) mice was similar to that in the control C57BL/6J mice. Moreover, DES exposure changed mRNA expression of inhibin-alpha (Inha) in 2-day-old C57BL/6J mice. These results suggest that inhibition of oocyte death by DES through ESR2 may be one of the triggers for polyovular follicle induction. The FAS system is also involved in neonatal oocyte death; however, reduction of oocyte death is not sufficient for polyovular follicle induction. The combination of increased Inha mRNA and reduction of oocyte death in the ovaries of mice by DES through ESR2 might be correlated with polyovular follicle induction.

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Section: Effects Of Estrogens On Female Reproductive Tract Developmentmentioning

confidence: 99%

“…Indeed, recent experimental studies on mice have highlighted the association of BPA with deformity of the reproductive tract and with gynaecologic cancers. In particular, it has been reported that exposure to BPA leads to earlier vaginal opening (Honma et al 2002), to altered ovarian morphology (Markey et al 2003;Kim et al, 2009), to proliferative lesions of the uterus (Newbold et al 2007a) and to a strong incidence of cystic ovaries (Newbold et al 2007a).The most dramatic report on FRT malformations induced by a Several studies have demonstrated that prenatal exposure of female to DES was associated with subsequent development of reproductive tract abnormalities. First, women prenatally exposed to DES presented with a "T shaped" uterus and an increased incidence of clear cell adenocarcimas of the vagina and cervix.…”

mentioning

confidence: 99%

The developing female genital tract: from genetics to epigenetics

Massé¹,

Watrin²,

Laurent³

et al. 2009

Int. J. Dev. Biol.

118

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The mammalian female reproductive tract develops from the Müllerian ducts which differentiate, in a cranial to caudal direction, into oviducts, uterine horns, cervix and the anterior vagina. The developmental processes taking place during this organogenesis are notably under the control of steroid hormones, such as members of the Wnt and Hox families, which regulate key developmental genes. At later stages, steroid hormones also participate in the development of the female genital tract. Chemical compounds homologous to steroids can thus act as agonists or antagonists in fetuses exposed to them. These so-called endocrine disruptors are nowadays found in increasing amounts in the environment and may therefore have a particular impact on such developing organs. Epidemiological studies have revealed that endocrine disruptors have had drastic effects on female health and fertility during the last decades. Furthermore, these adverse effects might be transmitted to subsequent generations through epigenetic modifications. Given the potential hazard of inherited epigenetic marks altering reproduction and/or human health, such molecular mechanisms must be urgently investigated. This review aims to summarize the cellular and molecular mechanisms involved in female genital tract development, to highlight key genes involved in this process and to present epigenetic mechanisms triggered by endocrine disruptors and their consequences in regard to female reproductive tract development. KEY WORDS: genital tract, Hox, Wnt, genetics, epigenetics Development of the urogenital system Relation between urinary and genital tractsMammalian genital tract development is closely related to the urinary system embryogenesis. This relation is ancient in evolution and phylogenetically well conserved. In simple organisms like annelids, they both consist in metamerized nephritic tubules composed of a ciliated funnel oriented towards the coelomic cavity and connected to a vascularised duct that opens to the exterior. This system is involved in metabolites and mature genital cells excretion. In higher vertebrates, the urogenital apparatus comprises the kidneys, gonads, urinary and reproductive ducts. The urinary tract embryonic formation is the result of a three steps process that gives rise to three successive structures emerging rostrocaudally in the intermediate mesoderm. Nephrotomes first develop in the cervical part of the embryo; they consist in a ciliated funnel emerging in the coelomic cavity and in a nephritic tubule Int. J. Dev. Biol. 53: 411-424 (2009) doi: 10.1387/ijdb.082680jm connected to a common excretory duct (the Wolffian duct, WD). At this stage, they form a primitive kidney called pronephros which is not functional. This transitory organ can only be observed in vertebrate embryos and agnathe larvae (Saxen and Sariola 1987;Bouchard et al. 2002). Then, while the pronephros is regressing, the mesonephros develops posteriorly, allowing the WD to grow in the same direction. This intermediary kidney, comprising a Bowman ...

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Effects of diethylstilbestrol on ovarian follicle development in neonatal mice

Cited by 33 publications

References 53 publications

Neonatal exposure to low doses of endosulfan induces implantation failure and disrupts uterine functional differentiation at the pre-implantation period in rats

Neonatal exposure to low doses of endosulfan induces implantation failure and disrupts uterine functional differentiation at the pre-implantation period in rats

Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries1

The developing female genital tract: from genetics to epigenetics

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