Spermatid

Mice exposed to 2,000 ppm of trichloroethylene, 4 hours/day for a 5-day period, had a significant increase in abnormal sperm morphology of 1% 28 days after the exposure (Land et al. 1981). No effect was seen at 200 ppm. A 6% increase in abnormal sperm was observed 4 weeks, but not 4 days or 10 weeks, after mice were exposed to 100 ppm trichloroethylene 7 hours per day for 5 days (Beliles et al. 1980). Based on the time after exposure at which sperm were affected, the study authors indicated that trichloroethylene damages sperm precursor cells but that spermatogonia were either unaffected or were capable of recovery. Reproductive performance was not tested in these studies. Another mouse study tested the effects of a 5-day exposure (6 hours/day) on spermatid micronuclei frequency no effects were observed at exposure levels of up to 500 ppm, the highest concentration tested (Allen et al. 1994). These results were interpreted as evidence that trichloroethylene did not cause meiotic chromosome breakage or loss. No treatment-related reproductive effects were seen in female rats exposed to 1,800 ppm trichloroethylene for 2 weeks (6 hours/day, 7 days/week) before mating (Dorfmueller et al. 1979). 

Allen JW, Collins BW, Evansky PA. 1994. Spermatid micronucleus analyses of trichloroethylene and chloral hydrate effects in mice. Mutat Res 323 81-88. 

With regard to the potential function of Raf-1 in mammalian germ cells, the testis is a site of abundant expression of c-ra/-l mRNAs. Northern blot and in situ hybridization analysis has shown that although c-ra/-l is expressed most abundantly in early pachytene spermatocytes, some transcripts were also detected in germ cells from type A and B spermatogonia through to the round spermatid stage (Wolfes et al., 1989 Wadewitz et al., 1993). 

B-raf, a member of the raf gene family of serine/threonine kinases, is expressed as two major transcripts of 4.0 kb and 2.6 kb in the mouse testis (Wadewitz et al., 1993). B-raf expression is limited to the germ cells and is particularly abundant in early spermatids. Northern hybridization analysis revealed that the two B-ra/transcripts are expressed in a stage-specific manner. Low levels of the 4.0-kb transcript are first... 

Also in need of further study is the function of Mos in male germ cells. It appears that Mos is expressed prior to meiosis of spermatocytes, consistent with the possibility that it acts in the initiation of meiosis and/or during progression from meiosis I to meiosis II. However, c-mos expression continues in postmeiotic spermatids, where it does not induce metaphase II arrest. This may be due to the absence of other components of cytostatic factor, but the role of c-mos expression in postmeiotic male germ cells remains unclear. 

The major FSH target in the male is the Sertoli cells, found in the walls of the seminiferous tubules of the testis. They function to anchor and nourish the spermatids, which subsequently are transformed into spermatozoa during the process of spermatogenesis. Sertoli cells also produce inhibin (discussed later), which functions as a negative feedback regulator of FSH. The major physiological effect of FSH in the male is thus sperm cell production. 

Medaka, Oryzias latipes adult males receiving single acute exposure of 0.64, 4.75, or 9.5 Gy Dose-dependent increase in total mutations in sperm, spermatids, and spermatogonia 16... 

Rat (Sprague- Dawley) 24 hr 5000 M (spermatid and spermatocyte degeneration, exfoliation) De Martino et al. 1987... 

Reproductive Effects. Reproductive effects have not been examined in humans after exposure to -hexane. A dominant-lethal test in mice showed no effect on male fertility (Litton Bionetics 1980). No effects were seen on reproductive tissues in male rats after intermediate-duration inhalation exposure at 500 ppm (IRDC 1981) or in either sex of mice after intermediate-duration inhalation exposure to up to 10,000 ppm -hexane (Dunnick et al. 1989 NTP 1991). However, inhalation exposure in male rats to higher concentrations of -hexane showed effects after acute-duration exposure to 5,000 ppm (spermatid and spermatocyte degeneration and exfoliation) and atrophy of testicular germinal epithelium after intermediate-duration exposure to 1,000 ppm (De Martino et al. 1987 Nylen et al. 1989). Testicular atrophy in rats was also noted after intermediate-duration oral exposure at 4,000 mg/kg/day (Krasavage et al. 1980). Similar to -hexane neurotoxicity after inhalation exposure, effects on the testes in rats can be reproduced by oral administration of the w-hexane metabolite 2,5-hexanedione (Chapin et al. 1982 ... 

Not only is it difficult to detect effects on male fertility because of group-size considerations, effects on male fertility mediated by decreased sperm production are also difficult to detect because of the normally huge excess of sperm included in a rat ejaculate. Sperm production can be decreased by up to 90% without effect on fertility (either pregnancy rate or litter size) in the rat. This is not the case for men, so the sperm excess in the rat represents a serious flaw in the rat model (see Working, 1988). To address this deficiency and improve the sensitivity of the model, it is advisable to determine the effects of the test agent on testes weights, testicular spermatid counts, and histopathology of the testes (preferably plastic sections) in the male fertility study and/or the 14-week toxicity study. In some cases, these parameters may be more predictive of possible effects on male fertility in humans than the fertility rate in rats. 

Amir D, Nicolle JC, Courot M. 1979. Changes induced in bull spermatids and testicular spermatozoa by a single peritesticular injection of ethylene dibromide. Int J Androl 2 162-170. 

Unni E, Zhang Y, Kangasniemi M, Saperstein W, Moss SB, Meistrich ML (1995) Stage-specific distribution of the spermatid-specific histone 2B in the rat testis. Biol Reprod 53 820-826... 

Drabent B, Saftig P, Bode C, Doenecke D (2000) Spermatogenesis proceeds normally in mice widiout linker histone Hit. Histochem Cell Biol 113 433-442 Drabent B, Benavente R, Hoyer-Fender S (2003) Histone Hit is not replaced by Hl.l or H1.2 in pachytene spermatocytes or spermatids of Hit-deficient mice. Cytogenet Genome Res 103 307—313 Ehrenhofer-Murray AE (2004) Chromatin dynamics at DNA replication, transcription and repair. Eur J Biochem 271 2335-2349... 

---