Seminiferous tubule

M (increased abnormal sperm Carlton et al. 1987 morphology and necrosis of TCP seminiferous tubules)... 

Rat 13wk (Fischer- 344) 7 d/wk (F) 220 M 430 M (significantly decreased absolute and relative testis weight and small testes atrophy of the seminiferous tubules) 65 F (hypertrophy inflammation of ovarian interstitial cells) NTP 1994 TCP... 

Mouse 25 wk (Swiss CD-1) (F) 250 (reduced number and proportion of live pups per litter and decreased fertility index) 250 M (decreased sperm motility and concentration, increased percentage of abnormal sperm, atrophy of the seminiferous tubules, decreased fertility index) Chapin et al. 1988 TCP... 

Organophosphate ester hydraulic fluids may cause adverse reproductive effects based on observations of testicular atrophy in rats after continuous inhalation exposure to 101 mg/m3 Durad MP280 for 90 days (MacEwen and Vemot 1983), loss of spermatic elements and degeneration in the seminiferous tubules in dogs given 20 subcutaneous injections of Cellulube 220 at doses ranging from 100 to 500 mg/kg/day... 

A mixed isomer preparation of TCP (containing <0.1% tri-ort/zo-cresyl phosphate) produced histological changes in reproductive organs in both sexes of rats and female mice in 13-week and 2-year bioassays (NTP 1994). Ovarian interstitial cell hypertrophy occurred in female mice and female rats exposed to gavage doses of 50-800 mg/kg/day for 13 weeks, in female rats exposed to dietary doses of 65 and 120 ng/kg/day for 13 weeks, and in female rats exposed to dietary doses of 9 or 18 mg/kg/day for 2 years (NTP 1994). Atrophy of the seminiferous tubules occurred in male rats that received gavage doses of 400 and 800 mg/kg/day for 13 weeks and in male rats exposed to dietary doses of 470 and 940 mg/kg/day for 13 weeks (NTP 1994). 

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. 

Mortality 71% at 6°C in 7 days nil at 21 °C in 9 days — but some with seizures and kidney histopathology. No spermatozoa in seminiferous tubules. Lead residues elevated in bone, liver, and brain in both groups, but more elevated in cold-stressed group... 

No adverse effects in 40 mg/kg BW group. High dose groups had skin damage (atrophy, acanthosis, hyperkeratinization) and testicular damage (abnormal seminiferous tubules, tubular lumens filled with degenerated sperm)... 

Krasowska, A. and T. Wlostowski. 1996. Photoperiodic elevation of testicular zinc protects seminiferous tubules against fluoride toxicity in the bank vole (Clethrionomys glareolus). Comp. Biochem. Physiol. 113C 81-84. 

Dose-related reduction in size of seminiferous tubules and in percentage of damaged tubules. High-dose group experienced 24-58% reduction in spermatogenesis (and high death rate) low-dose group 11-21% reduction and controls 0.5-6.1% reduction (Balash etal. 1987)... 

M (occasional abnormal cells Kamalu 1993 and seminiferous tubules Cassava devoid of normal germ cells)... 

Immunocytochemistry and in situ hybridization techniques were used to detect HIV-1 infected cells in the testis (P5), excurrent ducts, and prostate. Distinct pathologic changes were observed in the majority of testis of AIDS patients that included azoospermia, hyalinization of the boundary wall of seminiferous tubules, and lymphocytic infiltration of the interstitium. In the testis, many white blood cells were shown to the CD4 + HIV-1 positive cells of lymphocy-tic/monocytic morphology, found in the seminiferous tubules and interstitium of the testis, epididymal epithelium, and connective tissue of the epididymis and prostate. There was no evidence of active HIV-1 infection in germ cells or Sertoli cells of the seminiferous tubules or other epithelial cells lining the excurrent ducts or prostatic glands. 

Klinefelter syndrome (47,XXY) is seen in approximately 1 in 1,000 males (all individuals with this condition have a male phenotype because they have a Y chromosome). Klinefelter males are nearly always sterile because of atrophy of the seminiferous tubules. They tend to be taller than average, with abnormally long arms and legs. Breast development (gynecomastia) is seen in about one third of cases, and the IQ is on average 10-15 points below that of unaffected siblings. Individuals have also been seen with 48.XXXY and 49,XXXXY karyotypes the additional X chromosomes produce a more severely affected phenotype. 

Figure 19.1 A diagrammatic representation of the male reproductive tract. Much of the volume of the testes consists of convoluted seminiferous tubules in which the spermatozoa form. In the interstitial tissue that surrounds the seminiferous tubules are the Leydig cells which produce and secrete androgens, oes-tradiol and the peptides inhibin and activin. The epididymis is a single but convoluted tube. Sperm from the epididymis enter the vas deferens and pass through the ejaculatory duct into the urethra, mainly at the time of ejaculation. Just at the transition of the vas deferens to ejaculatory duct, two large glands, the seminal vesicles, drain into the two vasa deferentia. Prior to joining the urethra, the ejaculatory ducts pass through the prostate gland which lies below the bladder and surrounds the upper part of the urethra, into which prostatic fluid is secreted.

Figure 19.2 A diagram of a section through a human testis to show the general structure. The rete testis is a small structured component (not shown) that joins the seminiferous tubules to the vasa efferenb a and hence to the epididymis, where the sperm are stored.

The seminiferous tubules are lined by large cells, the Sertoli cells, which surround and almost enclose the developing spermatozoa in fact, it can be considered that much... 

The blood-testes barrier separates two parts of the seminiferous tubules, the part in which the spermatozoa are produced from the outer part which provides the blood supply. It has two functions (i) it prevents spermatozoa leaking into the blood or lymph, since proteins on the surface could act as antigens (ii) it maintains the distinct composition of fluid inside the tubules, which is necessary for spermatogenesis. 

Figure 19.3 The lifetime journey of a spermatozoon. The journey of the spermatozoa starts in the seminiferous tubules of the male and finishes in the oviduct of the female. For ejaculation they must travel from storage in the epididymis and vas deferens to the penile urethra, a distance of about 20 cm. The distance travelled in the female reproductive system is also about 20 cm.

Testicular histopathology revealed that major early changes after exposure to 1,3-DNB consisted of degeneration of germinal epithelium and sloughing of both spermatocytes and spermatids which in turn resulted in reduced sperm counts and reduced sperm mobility (Blackburn et al. 1988 Evenson etal. 1989b Linder etal. 1988, 1990 Reader etal. 1991). Disrupted spermatogenesis was also evidenced by a decrease in the number of seminiferous tubules in rats treated with 48 mg/kg of... 

DNB came with the observation of significantly increased levels of androgen-binding protein (ABP, released from Sertoli cells) in seminiferous tubule fluid, interstitial fluid, and serum in rats treated with 15 and 32 mg/kg of 1,3-DNB, respectively (Reader et al. 1991 Rehnberg et al. 1988). Further examination of early toxic effects of 15 mg/kg of 1,3-DNB revealed vacuolization and cytoplasmic retraction in Sertoli cells within the first 24 hours after exposure (Blackburn et al. 1988). Similar observations of Sertoli cell damage were made when 1,3-DNB was administered at a dose of 30 mg/kg (Reader et al. 1991). Data from these studies support the notion that Sertoli cells may be first and primary targets of the toxic effects of 1,3-DNB in seminiferous epithelium. 

Toxicology. 1,2-Dibromo-3-chloropropane (DBCP) is a mild central nervous system depressant and causes sterility in male workers due to a selective effect on seminiferous tubules. 

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