Developmental Diethylstilbestrol Exposure Alters Genetic Pathways of Uterine Cytodifferentiation

Huang, Weiwei; Yin, Yan; Bi, Qun; Chiang, Tung-Chin; Garner, Neysa; Vuoristo, Jussi; McLachlan, John A.; Ma, Liang

doi:10.1210/me.2004-0155

Cited by 64 publications

(66 citation statements)

References 60 publications

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“…Indeed, Msx2 is involved in vaginal epithelial differentiation and is required for Tgf-β2 and -β3 expression in the reproductive tract (Yin et al 2006). In mice, after exposure to DES, the level of Msx2 transcripts is significantly lower than physiological level in the developing uterus (Huang et al 2005) and in vaginal epithelium (Yin et al 2006). Moreover, a much more severe DES-induced vaginal phenotype is observed in Msx2-/-mutant mice exposed to DES, suggesting an important role for this gene during the estrogen-dependent growth of Müllerian derivatives and therefore in the protection of adverse effects of DES (Yin et al 2006).…”

Section: Effects Of Des On Developmental Genesmentioning

confidence: 99%

The developing female genital tract: from genetics to epigenetics

Massé¹,

Watrin²,

Laurent³

et al. 2009

Int. J. Dev. Biol.

115

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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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Section: Effects Of Des On Developmental Genesmentioning

confidence: 99%

The developing female genital tract: from genetics to epigenetics

Massé¹,

Watrin²,

Laurent³

et al. 2009

Int. J. Dev. Biol.

115

View full text Add to dashboard Cite

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“…In the genetically determined female and in the absence of testis-derived hormones, the Mü llerian ducts differentiate into the oviducts, uterus, cervix, and upper portion of the vagina and require the expression of Lim1 and Hox genes (for recent reviews see Huang et al, 2005;Yin and Ma, 2005;Viger et al, 2005). In the rodent, the Mü llerian ducts remain distinct forming a bipartite uterus with 2 horns and 2 cervical oses.…”

Section: Development Of the Female Reproductive Duct Systemmentioning

confidence: 99%

Evaluating rodent vaginal and uterine histology in toxicity studies

Li¹,

Davis

2007

Birth Defects Research Pt B

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“…Perinatal exposure to DES induced structural malformation of the reproductive tract and paraovarian cysts of mesonephric origin (Newbold, 2004). As exposure to DES changes the genetic status of the developing uterus, it induces abnormal cytodifferentiation in the uterus (Huang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Physiological Effects of Diethylstilbestrol Exposure on the Development of the Chicken Oviduct

Seo

Park²,

Lee³

et al. 2009

Journal of Animal Science and Technology

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Estrogen has dramatic effects on the development and function of the reproductive tract in mammals. Although diethylstilbestrol (DES) triggers the development of reproductive organs in immature animals, continued exposure to DES induces dysfunction of the female reproductive tract in mice. To investigate the effects of neonatal estrogen exposure on the reproductive tract of female chickens, we implanted DES pellets into the abdominal region of immature female chicks and then examined the effects of DES on the oviducts of both immature chicks and sexually mature chickens (30 weeks old). DES induced mass growth and differentiation of the oviduct in immature chicks. The chick oviduct increased by 2.7-and 29-fold in length and weight, respectively, following primary DES stimulation. In secondary DES stimulation, the length and weight of the chick oviduct increased by 4.5-and 74-fold, respectively. Additionally, DES treatments caused abnormal development of the infundibulum and magnum in hen oviducts. Furthermore, infundibulum abnormality gave rise to unusual ovulation of follicles and resulted in infertility and dysfunction of the magnum, such as less production of egg white proteins. Our results indicate that DES exposure during early developmental stages in chickens has detrimental effects on the development and maintenance of the female reproductive tract after sexual maturation.

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Developmental Diethylstilbestrol Exposure Alters Genetic Pathways of Uterine Cytodifferentiation

Cited by 64 publications

References 60 publications

The developing female genital tract: from genetics to epigenetics

The developing female genital tract: from genetics to epigenetics

Evaluating rodent vaginal and uterine histology in toxicity studies

Physiological Effects of Diethylstilbestrol Exposure on the Development of the Chicken Oviduct

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