Identification of male germ cells undergoing apoptosis in adult rats

Abstract

The possible role of apoptosis in spontaneous or induced germ cell death was investigated by treating adult male rats with either a GnRH antagonist (112.5 micrograms kg-1 day-1 for 14 days) or methoxyacetic acid (650 micrograms kg-1; single dose) or sham-treated with either of the vehicles (n = 3 per group). The antagonist virtually abolished gonadotrophin secretion, while methoxyacetic acid reduced serum testosterone concentrations and slightly increased those of FSH (neither significantly). Bands of low molecular mass characteristic of apoptotically degraded DNA were detected by electrophoresis in both treatment groups but not in the controls. Sectioned, Carnoy-fixed testes were screened for degenerating cells with periodic acid-Schiff's base and haemalaun or examined for apoptotic cells using a modified in situ end-labelling procedure. Periodic acid-Schiff's-stained dying cells were found in low numbers in control animals with a distribution and frequency that matched that of apoptotic cells. Degenerating germ cells identified by histology were present at certain stages of spermatogenesis after 2 weeks of antagonist treatment. A comparison of their distribution with that of end-labelled cells identified the cell death as apoptotic. Methoxyacetic acid caused a massive depletion of spermatocytes at stages IX-II, which was also found to be apoptotic. It is concluded that spontaneous germ cell death in adult rats is apoptotic and that both gonadotrophin ablation and administration of methoxyacetic acid can cause apoptosis in the germ cells of adult male rats, but via different routes.

Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition

“…Our initial studies led us to ethylene glycol monomethyl ether (EGME), a pervasive industrial solvent found in varnishes, paints, dyes, and fuel additives. Exposure to this compound and its primary metabolite MAA induce severe reproductive toxicity in both humans and rodents (11,12). Based on reports that toxic doses of EGME give rise to 5 mM MAA plasma levels in rodents and that similar concentrations of MAA are observed in the urine of humans after occupational EGME exposure (13,14), we treated cells with 5 mM MAA to achieve comparable MAA levels for our studies.…”

The cycle duration of the seminiferous epithelium remains unaltered during GnRH antagonist-induced testicular involution in rats and monkeys

“…Serum samples were assayed for testosterone and FSH concentrations using RIA as described (Brinkworth et al 1995, Chandolia et al 1991a. Limit of detection, and inter-and intra-assay coefficients of variation for testosterone assays were 0·67 nmol/l, 7·5% and 9·2% respectively.…”

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

“…Doxorubicin (DXR), an anthracycline that is a cornerstone of many chemotherapeutic regimens, is used for treating a wide spectrum of malignancies including both hematological and solid tumors. DXR has been previously studied for its deleterious effect on the gonadal epithelium in rodents, where it was shown to cause chromosome aberrations in spermatogonial cells (Au & Hsu 1980, Abraham & Fränz 1983, inhibition of DNA synthesis and induction of apoptosis (Brinkworth et al 1995, Blanco-Rodríguez & Martínez-García 1996, Shinoda et al 1999, Hou et al 2005. DXR has been shown to disrupt sperm maturation, reduce epididymal sperm concentration as well as alter spermatogonial DNA and sperm morphology (Meistrich et al 1990).…”