New Insights into the Role of Androgens in Wolffian Duct Stabilization in Male and Female Rodents

Welsh, Michelle Anne; Sharpe, Richard M.; Walker, Marion F; Smith, Lee B.; Saunders, Philippa

doi:10.1210/jcem.94.3.9997

Cited by 11 publications

(15 citation statements)

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“…During sexual differentiation in females, lack of androgen and Müllerian inhibiting substance results in the regression of the Wolffian duct (mesonephric tubules) and the development of the Müllerian duct, respectively (Behringer et al 1994, Welsh et al 2009). In addition, senescent cells in the mesonephric tubules are also thought to play a role in ensuring a properly timed regression of the tubules during fetal development through the clearance of senescent cells by infiltrating macrophages (Muñoz-Espín et al 2013), which results in a widespread apoptosis as a means to compensate for the delayed tubule regression.…”

Section: Cellular Senescence and Fetal Developmentmentioning

confidence: 99%

Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Velarde

Menon

2016

Journal of Endocrinology

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Cellular senescence is a phenomenon occurring when cells are no longer able to divide even after treatment with growth stimuli. Because senescent cells are typically associated with aging and age-related diseases, cellular senescence is hypothesized to contribute to the age-related decline in reproductive function. However, some data suggest that senescent cells may also be important for normal physiological functions during pregnancy. Herein, we review the positive and negative effects of cellular senescence on female reproductive aging and pregnancy. We discuss how senescent cells accelerate female reproductive aging by promoting the decline in the number of ovarian follicles and increasing complications during pregnancy. We also describe how cellular senescence plays an important role in placental and fetal development as a beneficial process, ensuring proper homeostasis during pregnancy.

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Section: Cellular Senescence and Fetal Developmentmentioning

confidence: 99%

Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Velarde

Menon

2016

Journal of Endocrinology

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“…The Wolffian and Mülle-rian ducts attach to the urogenital sinus at the sinus ridge, and the sex ducts themselves undergo sexual differentiation or degradation in response to hormonal cues. By E17.5, the rostral Müllerian and Wolffian ducts have degenerated in males and females, respectively (13,23). To determine if the sinus ridge position is influenced by differential development of the male and female sex ducts, we examined Wolffian and Müllerian duct development in females treated with Me-T and in males with Ar deleted by Hoxa13 cre .…”

Section: Sinus Usingmentioning

confidence: 99%

Spatiotemporal dynamics of androgen signaling underlie sexual differentiation and congenital malformations of the urethra and vagina

Larkins

Enriquez

Cohn

2016

Proc. Natl. Acad. Sci. U.S.A.

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Disorders of sex development (DSDs) are congenital anomalies that affect sexual differentiation of genitourinary organs and secondary sex characters. A common cause of female genital virilization is congenital adrenal hyperplasia (CAH), in which excess androgen production during development of 46XX females can result in vaginal atresia, masculinization of the urethra, a single urogenital sinus, and clitoral hypertrophy or ambiguous external genitalia. Development of the vagina depends on sexual differentiation of the urogenital sinus ridge, an epithelial thickening that forms where the sex ducts attach to the anterior urethra. In females, the sinus ridge descends posteriorly to allow the vaginal opening to form in the vulva, whereas in males and in females with CAH, androgens inhibit descent of the sinus ridge. The mechanisms that regulate development of the female urethra and vagina are largely unknown. Here we show that the timing and duration of, and the cell population targeted by, androgen signaling determine the position of vaginal attachment to the urethra. Manipulations of androgen signaling in utero reveal a temporal window of development when sinus ridge fate is determined. Cell type-specific genetic deletions of androgen receptor (Ar) identify a subpopulation of mesenchymal cells that regulate sinus ridge morphogenesis. These results reveal a common mechanism that coordinates development of the vagina and feminization of the urethra, which may account for development of a single urogenital sinus in females exposed to excessive androgen during a critical period of prenatal development.vagina | urethra | androgen | mouse | development

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“…The initial phase encompasses regression of the duct in females and androgenmediated stabilisation and retention of the ducts in males. This occurs from about E13.5-E16 in mice and rats, by which stage little remains of the WD in females [Staack et al, 2003;Welsh et al, 2009]. Following this is a phase of differentiation in males which includes tubular elongation and marked convolution of the cranial end accompanied by cytological and morphological differentiation of the epididymis and vas deferens [Welsh et al, 2006].…”

Section: Hormonal Regulation Of Wd Differentiationmentioning

confidence: 99%

“…At the caudal end, the seminal vesicle starts to form. Intriguingly, there are critical time windows for the hormonal priming that regulates WD development as well as other aspects of virilisation [Welsh et al, 2009Macleod et al, 2010]. Blocking androgen action with flutamide after this critical time window, but before morphological differentiation, does not prevent formation of a vas and epididymis [Welsh et al, 2006[Welsh et al, , 2009Macleod et al, 2010].…”

Section: Hormonal Regulation Of Wd Differentiationmentioning

confidence: 99%

Wolffian Duct Development

Shaw

Renfree²

2014

Sex Dev

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The Wolffian ducts (WDs) are the progenitors of the epididymis, vas deferens and seminal vesicles. They form initially as nephric ducts that acquire connection to the developing testis as the mesonephros regresses. The development of the WDs is dependent on androgens. Conventionally, the active androgen is believed to be testosterone delivered locally rather than via the systemic circulation. However, recent studies in marsupials show that 5α-reduced steroids are essential and that these can induce virilisation even when they are delivered via the systemic circulation. The development of the WDs involves an interplay between the duct epithelium and underlying mesenchyme; androgen receptors in both the epithelium and mesenchyme are needed. The epidermal growth factor and epidermal growth factor receptor may play a role, possibly via activation of androgen receptor. The formation of the epididymis involves a complex morphogenetic program to achieve the normal pattern of coiling, formation of septae, and regional functional differentiation. In part, this process may be mediated by inhibin beta A as well as by genes from the HOX cluster. Whilst the development of the WD is androgen dependent, it is clear that there is a complex interplay between androgens, genes and growth factors in the tissues that leads to the formation of the complex anatomy of the male reproductive duct system in the adult.

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New Insights into the Role of Androgens in Wolffian Duct Stabilization in Male and Female Rodents

Cited by 11 publications

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Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Spatiotemporal dynamics of androgen signaling underlie sexual differentiation and congenital malformations of the urethra and vagina

Wolffian Duct Development

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