Castration Induces Apoptosis in the Mouse Epididymis during Postnatal Development.

Abstract

The effect of castration on apoptosis in the mouse epididymis during postnatal development was examined. The weight of the epididymis slowly increased from day 0 (day of birth) to day 20 after birth, followed by a rapid increase thereafter. Castration on days 0, 5, 10, 20, 30, 40 and 60 increased apoptotic indices (percentages of apoptotic cells) of epithelia of the caput (head), corpus (body), and cauda (tail) epididymis, their apoptotic indices reaching maximal levels on day 2 after castration with the exception of a maximal apoptotic index on day 4 in the tail after castration on day 60. The maximal levels of apoptotic indices of the head, body and tail after castration on days 0, 5, 10 and 20 were significantly lower than those after castration on days 40 and 60. DNAs extracted from the epididymides 2 days after castration on days 0, 5, 10 and 60 showed a ladder pattern on agarose gel electrophoresis, which is a characteristic of apoptosis. When testosterone propionate (10 microg/g body weight) was injected twice a day into mice which had been castrated on day 10, 30 or 60, the increases in apoptotic indices of the head, body and tail of the epididymis were completely inhibited. The weights of the paired epididymides 6 days after castration on days 0, 5, 10, 20, 30, 40 and 60 were significantly lower than those of sham-operated mice, indicating the secretion of androgen by the testes from birth to adulthood. The present results indicated that androgen deprivation caused by castration induces apoptosis in the epithelium of the epididymis of mice from birth to adulthood, and suggested that a proportion of epithelial cells, the survival of which is dependent on the testes, is smaller in the epididymides during a slow growth stage than in the epididymides after this stage.

Fos Plays No Role in Apoptosis of Epithelia in the Mouse Male Accessory Sex Organs and Uterus

“…Our previous studies [13,14] showed that castration of prepubertal mice induced the lesser extents of apoptosis in the male accessory sex organs such as SV and Ep Castrated male and female mice were given 5 daily injections of TP and E 2 , respectively. Body weight of mice and weights of the male accessory sex organs and the uterus on day 1 (the day following the last injection) were measured.…”

“…To avoid the effect of Fos on production of steroid hormones by gonads, we examined apoptosis after the cessation of administration of androgen or estrogen to castrated mice. In addition, we also compared apoptosis in epithelia of the accessory sex organs of adult c-fos knockout mice with apoptosis in young normal mice because the body weights of adult c-fos knockout mice were much lighter than those of adult normal mice, suggesting the retarded development of adult c-fos-knockout mice and because our previous studies [13,14] showed that the extents of apoptosis in the accessory sex organs of young mice after castration were much less than those of adult mice, indicating that the extents of apoptosis in the accessory sex organs differ depending on the developmental stages of mice.…”

Androgen Receptor Expression in the Caput Epididymal Epithelium Is Essential for Development of the Initial Segment and Epididymal Spermatozoa Transit

“…At postnatal ages, acute withdrawal of androgens after orchidectomy results in apoptosis of epididymal epithelial principal cells (14,15) and dedifferentiation of the caput epididymal epithelium to a 'precursor' state (16), demonstrating that androgens are important for maintenance of epithelial cell identity. However, whether this impact of testosterone withdrawal is due to direct action on the epithelial cells or indirect action via the stromal cells remains unclear, as both cell types express AR.…”

Testosterone deficiency accompanied by testicular and epididymal abnormalities in TMF−/− mice

“…Administration of testosterone to wt and TMF À/À mice Six wt mice at the age of 18 weeks and 6 TMF À/À age-matched mice were divided into four groups: three wt and three TMF À/À mice were treated each with a control, 0.1 ml oily solution (vehicle)/day/mouse without testosterone, three wt and three TMF À/À mice were treated each with 0.5 mg/day/mouse of a testosterone-enanthate solution (Bayer pharmaceuticals), (Fan and Robaire, 1998;Takagi-Morishita et al, 2002). All solutions were injected daily, intra peritoneally (ip), using a 1 ml syringe with a 25G needle, for 12 days.…”

“…Depletion of elongating spermatids, spermatids retention and Leydig cell hyperplasia are features of testosterone depletion (Creasy, 1997(Creasy, , 2001. Similarly, apoptotic death of the epididymal epithelium is seen in orchidectomized mice (Fan and Robaire, 1998;Takagi-Morishita et al, 2002) and in rats with reduced testosterone (Creasy, 2001). To test this possibility, serum testosterone levels were determined in eleven wt males with the average age of 30 weeks, as well as in eleven TMF À/À male mice of the same age.…”