Gonadal toxicity

Singh SK, Pandey RS. 1989. Gonadal toxicity of short term chronic endosulfan exposure to male rats. Indian J Exp Biol 27 341-346. 

Increased clearance of steroid hormones due to induction of hepatic biotransformation enzymes following chemical exposure often has been cited as a possible mechanism by which toxicants could lower circulating testosterone or 17/3-estradiol levels. While enhanced clearance of sex steroids has been demonstrated following chemical exposure and induction of hepatic biotransformation enzymes, elegant feedback control mechanisms tend to ensure that more hormone is produced and homeostasis is maintained (Figure 17.2). Enhanced clearance of sex steroids can contribute to endocrine disruption if the toxicity also results in impaired hormone synthesis (i.e., gonadal toxicity or interference with the feedback control of hormone synthesis). 2,3,7,8-Tetrachlorodibenzodioxin appears to lower circulating sex steroid levels via this dual effect. 

Gonadal toxicity has been documented in both men and women receiving cyclophosphamide (4). In men, the incidence of transient or permanent oligospermia/azoo-spermia is 50-90%, and in prepubertal patients spermatogenesis will more readily return to normal than adults. In one study, testosterone prophylaxis given at the same time as cyclophosphamide reduced the incidence of disorders of spermatogenesis and accelerated spermatogenesis recovery after cyclophosphamide discontinuation, but few patients were evaluable (59). 

Sexual complaints attributed to interferon alfa, namely decreased hbido, impotence, or erectile failure, are usually concomitant to other neuropsychiatric symptoms, and cases of reversible impotence are anecdotal (315). The mechanisms accounting for these adverse effects are unclear, and changes in sex hormone concentrations have not been consistently reported. In one study in healthy women, interferon alfa produced falls in serum progesterone and estradiol concentrations (316), but neither impairment of libido nor impairment of fertility has apparently been reported in women. No evidence of gonadal toxicity or sexual dysfunction was found in 43 men with hairy cell leukemia who received interferon alfa for 2-12 months compared with 33 patients who... 

Lamont EB, Schilsky RL. Gonadal toxicity and teratogenicity after cytotoxic chemotherapy. In Lipp HP, editor. Anticancer Drug Toxicity Prevention, Management and Clinical Pharmacokinetics. New York-Basel Marcel Dekker Inc, 1999 491-523. 

Based on comparative studies of the relative gonadal toxicity of several antineoplastic agents in experimental models and humans, the vinca alkaloids vinblastine and vincristine have negligible potency for killing stem cells. Permanent recovery of sperm counts and preserved ovarian function, depending on the patient s age at the time of... 

Oral steroid is most frequently used for maintenance treatment (prednisolone 5 to 15 mg/day or equivalent). " Alternate-day regimens, although not evaluated, are often used in children to minimize growth retardation. Monthly pulse IV steroids in conjunction with cyclophosphamide resulted in more sustained remission, fewer relapses, and no significant increase in side effects. This combination has also been shown by meta-analysis to be more beneficial than steroid or cyclophosphamide alone. Cyclophosphamide, because of its bladder and gonadal toxicity, has been given as monthly and then bimonthly intravenous injection, instead of daily administration, for up to 2 or more years. However, toxicity is still a concern. A recent trial in Emope showed that after initial lower pulse doses of IV cyclophosphamide, oral azathioprine was able to attain remission rates similar to those of higher initial pulse doses of cyclophosphamide with quarterly foUow-up doses. ... 

Kackar R, Srivastava MK, Raizada RB. 1997a. Induction of gonadal toxicity to male rats after chronic exposure to mancozeb. Indust Health 35 104-111. 

It needs to be noted that a toxic effect on the reproductive system may be mediated through alterations in normal functions of the central nervous system, gonads (ovaries, testicles), or on the pharmacokinetics of reproductive hormones. ... 

Leapfrog, Rana dalmutina, larvae, exposed during formation of gonadal structures 9000 Toxic effect on larval gonad, especially on germ cells of ovarian structure 81... 

Issam C, Samir H, Zohra H et al (2009) Toxic responses to deltamethrin low doses on gonads, sex hormones and lipoperoxidation in male rats following subcutaneous treatments. J Toxicol Sci 34 663-670... 

Gonads (10 g) of the pufferfish Fugu pardalis are extracted with 25 mL of 0.02 M acetic acid in a boiling water bath for 10 min. After being cooled to room temperature, the extract is filtered. The filtrate is passed through an Amberlite CG-50 column (NH, 1.2x3 cm). The column is developed with 50 mL each of water and 0.5 M acetic acid. A defatting step may be introduced prior to the column treatment when fat-rich tissues like livers are employed. The toxic eluate is concentrated in vacuo and made up to 20 mL with water. A 50- jaL portion of the solution is analyzed by HPLC. 

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