Depression Of Spermatogenesis Research Articles

Carbaryl, A Pesticide Causes “Reproductive Toxicity” in Albino Rats

The key to man’s health lies largely in his environment & often man is responsible for the pollution of his environment through urbanization, industrialization and other human activities for example commercial agriculture and garden pest control etc. by using pesticides. Pesticides, though present in the environment in small quantities as compared to other contaminants such as industrial wastes and fertilizers, account for public and scientific concern due to their high biological activity. In the recent years, use of carbamate insecticides has gained importance due to ban of the insecticides belonging to Organochlorine groups that is D.D.T., Aldrin, Lindane and Endosulfan. These pesticides have a tendency to persist and have potential to bioaccumulate in the body Kamrin [1]. Concern about the susceptibility of the male reproductive system to drugs or environmental agents has assumed an increasing extent. The outcome of such exposures have included not only reduced fertility but also embryo/fetal loss, birth defects, childhood cancer, and other postnatal or functional deficits. Carbaryl is one of the most important insecticides as it is widely produced and used which has prompted us to initiate this study . The present study was conducted on 40 male Wistar albino rats as experimental animals. The rats were procured from the Animals House of the Department of Pharmacology, Government Medical College, Jammu. The rats were divided in four groups as normal control group I, group II, group III and group IV. All the rats were group housed and were fed with standard pellet diet and water for two weeks. After two weeks, the rats of group I were left as such and rats of groups II, III and IV were given 50 mg, 100 mg and 200 mg/kg body weight/day of carbaryl drug in 0.2 ml of groundnut oil orally, 6 days/week for 60 days, respectively. After 60 days, all the rats were anaesthetized by keeping them in an inverted glass jar containing large piece of cotton soaked in anaesthetic ether. The testis were dissected out from each rat and were cut into smaller pieces. These pieces were immediately fixed in 10% formalin. The blocks were prepared for section cutting with a microtome by paraffin wax embedding method. The sections of 7 μ thickness were mounted on glass slides and were stained by H&E and Masson’s trichome stain. The following findings are drawn from the study:- (1) There is variation in the shape of seminiferous tubules of testis. (2) There is sloughing of the germinal cells from the basement membrane. (3) There is depressed spermatogenesis and loss of sperms. (4) Some tubules are showing accumulation of cellular masses in the lumen of seminiferous tubules of testis. (5) Interstitial spaces are showing the oedema. (6) Degenerated Leydig cells are also seen. These findings are highly conclusive of reproductive toxicity produced by an insecticide, Carbaryl. It is concluded that the toxic effects are more pronounced in the peripheral parts of the sections of testis. Moreover, intensity of toxic effects both in peripheral and central parts increases with increase in dosage of the carbaryl drug.

Effect of Zingiber Officinale (Ginger) on Sodium Arsenite- Induced Reproductive Toxicity in Male Rats

Arsenite is a major environmental chemical and a known reproductive toxicant via the depression of spermatogenesis and androgenesis in males. The possibility of sodium arsenite reproductive toxicity been caused by autooxidation was investigated in this study taking advantage of the anti-oxidant properties of ginger and its androgenic activities. The effect of exposure to sodium arsenite (10 mg/kg BW/day) by gavage via oral cannula without or with aqueous ginger extract (500mg/kg BW/day) co-treatments for 30 days was evaluated in adult male rats. The weight of the reproductive organs, sperm count, motility, and morphology were evaluated. Plasma FSH, LH and testosterone levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants enzymes likes GSH, SOD, CAT were assessed. Sodium arsenite treatment decreased the reproductive organs weight: testis, epididymis, prostate and seminal vesicle; sperm functions: count, motility and normal morphology; plasma hormones level: FSH, LH and testosterone. There was a decrease in the activities of GSH, SOD and CAT as well as an increase in MDA concentration. Co-administration of aqueous ginger extract with arsenite was found to protect against adverse change in the reproductive organ weight, attenuate the decrease in sperm functions, enhance plasma reproductive hormones level along with increased antioxidants activities and reduced peroxidation. This study showed that sodium arsenite apart from being a hormonal disrupter also causes oxidative stress which contributed to the reproductive damage in the male rats. The protective effects of ginger on reproductive toxicity and oxidative stress as evidenced by the clear restoration of sperm functions, testicular steroidogenesis and reproductive organo-somatic indices could be attributed to its antioxidants and androgenic properties. Key Words : Arsenite, Ginger, Antioxidants and Sperm.

Azoospermia in a renal transplant recipient during sirolimus (rapamycin) treatment

Sirolimus is used as a powerful immunosuppressant drug in patients after organ transplantation. It was shown to block spermatogenesis by interrupting the stem cell factor/c-kit system. Oligozoospermia was shown in single patients. In addition, a decrease of testosterone and an increase of gonadotropin levels were observed. We report on a young patient who showed azoospermia during the treatment with sirolimus after renal transplantation. After changing the immunosuppression to tacrolimus, spermatogenesis of the patient recovered. Five months after cessation of the treatment with sirolimus, a sperm concentration of 8 x 10(6) ml(-1) was found. Depression of spermatogenesis is an important side effect in younger men who aspire paternity, so that waiving of sirolimus is advisable in these patients.

CAG repeat length in an infertile male population of Irish origin

The androgen receptor (AR) gene, located on the X chromosome, is an important regulator of human spermatogenesis. In the past decade, the link between the CAG polyglutamine tract, situated on exon one of the AR gene, and reduced spermatogenesis has become a controversial one. Alterations in the length of the CAG polyglutamine tract have been associated with prostate cancer at a reduced intrinsic length and neuromuscular diseases at a CAG repeat length of > or = 40. Minimal intermediate increases have been linked with depressed spermatogenesis in infertile males. Asian and Australian groups have published an association between increased CAG repeat length and reduced spermatogenesis while many European studies have found no such association. The aim of this study was to document the association between increased CAG repeat length and reduced spermatogenesis in a group of Irish infertile males and controls known to have fathered at least one child. The study employed the ABI 377 DNA sequencer to size the CAG repeat region of exon one of the AR gene in each group. Statistical analysis revealed no actual link between the length of the CAG tract and a reduction of spermatogenesis in a cohort of infertile patients (n = 66) of Irish ethnic origin when compared to a fertile control group (n = 77) (p = 0.599).

Sex, infertility and the molecular biology of the androgen receptor.

Mutations that totally disrupt androgen receptor function cause the well known testicular feminizing syndrome or complete androgen insensitivity syndrome, wherein a 46 XY individual is completely feminized at birth. Recently it has been increasingly obvious that androgen receptor mutations not only result in the complete androgen insensitivity syndrome, but can cause a wide spectrum of milder insensitivity syndromes including ambiguous genitalia in newborn infants, and 'idiopathic' male infertility in otherwise normal males. Characterization of the molecular and structural mechanisms of androgen receptor dysfunction in these cases has led to directed hormonal therapy. Thus the differential response of a Met807Thr mutant androgen receptor to dihydrotestosterone but not testosterone, have been used to restore male genital development in an infant with partial AIS. Of greater significance, because they affect larger numbers of patients, are the mutations and polymorphisms that result in depressed spermatogenesis and male infertility in phenotypic males. Studies involving Singaporean, Australian, North American and Japanese subjects have established that increases in length of a trinucleotide repeat (CAG) tract, encoding a polyglutamine stretch in the transactivation domain of the androgen receptor, are associated with increased risk of defective spermatogenesis and undermasculinization. Independent of the CAG repeats, missense amino-acid substitutions in the ligand-binding domain, involving residues 727, 798 and 886 cause infertility through a novel mechanism. Pathogenicity is transmitted, not through defective ligand binding, but through defective protein-protein interactions between receptor domains and coactivator proteins that are essential for gene transcription. Elucidation of the molecular and structural basis of androgen receptor dysfunction in these cases allows precise genetic counseling and can lead to the design of rational hormonal therapy.

Longitudinal Gonadal Steroid Excretion in Free-Living Male and Female Meerkats (Suricata suricatta)

Slender-tailed meerkats (Suricata suricatta) are small, diurnal, cooperatively breeding mongooses of the family Herpestidae. A prerequisite to fully understanding the mating system of meerkats is the development of a normative reproductive–endocrine database. This study examined longitudinal gonadal steroid excretion in all adult and juvenile individuals of both sexes within a social group of free-living meerkats sampled across an entire breeding season. The specific objectives of this study were to (1) validate noninvasive (fecal and urinary) gonadal steroid hormone monitoring techniques in male (testosterone) and female (estrogens, progestagens) meerkats; (2) test the feasibility of using these noninvasive methods under field conditions; (3) characterize the endocrine correlates associated with the female reproductive cycle, including estrus, gestation, and postpartum estrus; (4) examine longitudinal androgen excretion in males; and (5) determine whether social status (i.e., dominant versus subordinate) affected gonadal steroid excretion. In females, the results demonstrated the physiological validity of noninvasive monitoring in meerkats by corresponding excretory hormone concentrations to major reproductive events (i.e., estrous, pregnancy, parturition). Hormone excretory patterns during estrous intervals suggested possible mechanisms whereby reproductive suppression may operate in female meerkats. In males, androgen excretion did not correspond to changes in reproductive and aggressive behaviors, suggesting that dominance, and hence breeding access to females, was not regulated strictly by gonadal steroid production. The consistency in androgen excretion among male meerkats indicated that reproductive suppression may be mediated by behavioral (i.e., intermale aggression) rather than physiological (i.e., depressed spermatogenesis) mechanisms.

Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility

Objective: To determine whether changes in the polymorphic trinucleotide (CAG) tract of the androgen receptor gene are associated with spermatogenic defects in patients with male infertility. Design: Case–control study of two ethnic groups. Setting: University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital, Singapore. Participant(s): Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls. Main Outcome Measure(s): Size of androgen receptor CAG alleles according to fluorescent-labeled polymerase chain reaction and automated analysis using Genescan software (PE Biosystems Asia, Singapore), and statistical examination of its relation to clinical variables. Result(s): In U.S. patients, the mean androgen receptor CAG length was significantly longer in infertile patients than in fertile controls (21.95 ± 0.31 vs. 20.72 ± 0.52). Logistic regression showed that each unit increase in CAG length was associated with a 20% increase in the odds of being azoospermic. The odds ratio for azoospermia was sevenfold higher for patients with ≥26 CAG repeats than in those with <26 CAG repeats. Although mean CAG length in Singapore patients was longer than in the U.S. samples, long androgen receptor CAG alleles were significantly related to male infertility in both populations. Conclusion(s): Long (≥26) androgen receptor CAG alleles, which are found in up to 25% of azoospermic men, are associated with male infertility and defective spermatogenesis. Conception in these men is possible with assisted reproductive technologies, as many have spermatozoa in their testes.

Human Androgen Receptor Mutation Disrupts Ternary Interactions between Ligand, Receptor Domains, and the Coactivator TIF2 (Transcription Intermediary Factor 2)

The androgen receptor (AR) is a ligand-dependent X-linked nuclear transcription factor regulating male sexual development and spermatogenesis. The receptor is activated when androgen binds to the C-terminal ligand-binding domain (LBD), triggering a cascade of molecular events, including interactions between the LBD and the N-terminal transactivation domain (TAD), and the recruitment of transcriptional coactivators. A nonconservative asparagine to lysine substitution in AR residue 727 was encountered in a phenotypically normal man with subfertility and depressed spermatogenesis. This N727K mutation, although located in the LBD, did not alter any ligand-binding characteristic of the AR in the patient's fibroblasts or when expressed in heterologous cells. Nonetheless, the mutant AR displayed only half of wild-type transactivation capacity when exposed to physiological or synthetic androgens. This transactivation defect was consistently present when examined with two different reporter systems in three cell lines, using three androgen-driven promoters (including the complex human prostate-specific antigen promoter), confirming the pathogenicity of the mutation. In mammalian two-hybrid assays, N727K disrupted LBD interactions with the AR TAD and with the coactivator, transcription intermediary factor 2 (TIF2). Strikingly, the transactivation defect of the mutant AR can be rectified in vitro with mesterolone, consistent with the ability of this androgen analog to restore sperm production in vivo. Mesterolone, but not the physiological androgen dihydrotestosterone, restored mutant LBD interactions with the TAD and with TIF2, when expressed as fusion proteins in the two-hybrid assay. Our data support an emerging paradigm with respect to AR mutations in the LBD and male infertility: pathogenicity is transmitted through reduced interdomain and coactivator interactions, and androgen analogs that are corrective in vitro may indicate hormonal therapy.

Effects of Organoantimony(III) Compounds of Sterically Hindered Bifunctional Tetradentate Ligands on the Reproductive System of Male Rats

The antifertility activity of organoantimony(III) complexes PhSb[RC(NC6H4S)CH2(NC6H4S)CR′] {R' = CH3 (R1) and R = R' = CF3 (R2)} derived from corresponding sterically hinlered bifuinctional tetradentate ligands in the male rats was determined. The administration of compounds R1 and R2 at the dose level of 20 mg/kg. b. wt. siignificantly reduced the weights of testes and epididymides. Auxiliary glands showed a significant reduction after the treatment of compound R1 only. Treated animals showed a notable depression of spermatogenesis. The preleptotene spermatocytes were decreased by 76.19 and 47.06; the secondary spermatocytes by 87.4% and 54.87337; and the step-19 spermatids by 72.9 and 46.77% respectively, following the compound R1 and R2 treatment. Reduced sperm count and motility resulted in 100% negative fertility in both the treated groups. A significant fall in the content of various biochemical parameters of eproductive tissues was observed after R1 and R2 treatment in comparison to controls.

Androgen receptor transactivation domain and control of spermatogenesis.

Male sex steroids (androgens) are important for maintaining sperm production and growth of the accessory sex organ, the prostate gland. This article examines the role of the androgen receptor (AR) in the control of spermatogenesis and focusses on the N-terminal transactivation domain of the receptor, a poorly studied region that is essential for receptor function. This domain is of great interest because of its causative relationship to a fatal neuromuscular disease, spinal bulbar muscular atrophy (Kennedy's syndrome). Genetic screening of the transactivation domain of the AR gene of 153 patients presenting solely with defective spermatogenesis and male infertility, and of over 72 healthy fertile controls was performed. Up to 20% of infertile males have reduced androgenicity caused by an increase in length of a polymorphic trinucleotide (CAG) repeat segment, encoding a polyglutamine tract, of the androgen receptor. The increased risk of male infertility associated with long CAG lengths is associated with reduced risk of prostate cancer. Conversely, short polyglutamine tracts are associated with increased risk of prostate cancer but a reduced risk of male infertility. Thus depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of androgen receptor transactivation function. Improved understanding of androgen receptor action in these two important public health concerns could lead to rational and effective prevention and therapy.

Androgen receptor transactivation domain and control of spermatogenesis

Male sex steroids (androgens) are important for maintaining sperm production and growth of the accessory sex organ, the prostate gland. This article examines the role of the androgen receptor (AR) in the control of spermatogenesis and focusses on the N-terminal transactivation domain of the receptor, a poorly studied region that is essential for receptor function. This domain is of great interest because of its causative relationship to a fatal neuromuscular disease, spinal bulbar muscular atrophy (Kennedy's syndrome). Genetic screening of the transactivation domain of the AR gene of 153 patients presenting solely with defective spermatogenesis and male infertility, and of over 72 healthy fertile controls was performed. Up to 20% of infertile males have reduced androgenicity caused by an increase in length of a polymorphic trinucleotide (CAG) repeat segment, encoding a polyglutamine tract, of the androgen receptor. The increased risk of male infertility associated with long CAG lengths is associated with reduced risk of prostate cancer. Conversely, short polyglutamine tracts are associated with increased risk of prostate cancer but a reduced risk of male infertility. Thus depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of androgen receptor transactivation function. Improved understanding of androgen receptor action in these two important public health concerns could lead to rational and effective prevention and therapy.

Male infertility and the androgen receptor: molecular, clinical and therapeutic aspects

Idiopathic male infertility has previously been diagnosed imprecisely, and has been treated using regimes that are not based on a clear understanding of the underlying pathophysiology; however, this is gradually changing, and a more rational approach is being adopted. Testosterone and its metabolite, DHT, is allimportant for the maintenance of sperm production and this has led us to examine the AR for causes of male infertility. Some, but not all, androgen-binding studies have indicated that in a certain proportion of cases of male infertility, defective androgen binding occurs. The cloning of the AR gene allowed for a more rigorous examination of the molecular pathogenesis which turned out to be both subtle and heterogeneous. Genetic screening of a large group of men with defective spermatogenesis has indicated that up to 30% of infertile males could have variations in the androgenicity of their AR caused by polymorphisms in the length of the polyglutamine tract. Substitutions of the AR in the LBD and the DBD can also lead to reduced AR function and male infertility. In this regard, it is interesting to note that depressed spermatogenesis and prostate cancer represent opposite ends of the spectrum of AR action (Figure 6). Although empirical treatment of AR mutants in some cases has been shown to restore normal AR function and to improve spermatogenesis, a fully rational basis of treatment has to be based on an understanding of the crystallographic structure of the AR LBD. A full understanding could lead to the construction and the administration of ‘designer’ androgen analogues to treat male infertility caused by mutations of the AR gene.

Testicular morphology and function in varicocele patients: pre-operative and post-operative histopathology.

The organic effects of varicocele on testicular histology were studied in bilateral testicular biopsies obtained from 30 infertile men during varicocele repair and 3 to 6 months post-operatively, using light microscopy. Before surgery and at follow-up, semen analyses were performed. The results showed a substantial improvement in semen quality in 22 cases post-operatively. Pre-operative biopsies showed depressed spermatogenesis with a predominant picture of maturation arrest, sloughing of spermatogenic epithelium, an increase in Leydig cells, thickening of tubular basement membranes and interstitial blood vessel walls with narrowing of their lumina, and increased deposition of interstitial fibrous tissue. Post-operatively, spermatogenesis improved in 22 cases, with increased mean tubular scores together with diminution in epithelial cell sloughing. The increased prominence of Leydig cells reverted to normal in 18 cases. The changes in tubular basement membranes, interstitium and interstitial blood vessels were unaffected.

Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.

Possible protective effects of the agonist [D-Trp6]LH-RH (analog of luteinizing hormone-releasing hormone in which Gly-6 is replaced by D-tryptophan) and antagonist N-Ac-[D-Phe(pCI)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group given 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist (1000 micrograms/kg of body weight per day) showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Thus, pretreatment of rats with LH-RH antagonist, by reversibly inhibiting gonadal function, protected the germinal cells of the testes against damaging effects of x-rays. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist [D-Trp6]LH-RH, liberating 25 micrograms of the agonist per day. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. In spite of pretreatment with [D-Trp6]LH-RH, testicular weights were significantly lower and LH or FSH levels were elevated in the irradiated groups as compared with nonirradiated controls. The recovery of spermatogenesis was incomplete, and there was a decrease in the number of germinal cells after 415 rads and especially after 622 rads. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist [D-Trp6]LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

Subchronic and Chronic Toxicity Studies of 2,4-Dinitrotoluene. Part II. CD® Rats

Subchronic and chronic toxicities of 2,4-dinitrotoluene were studied in CD® rats. Feeding of 2,4-dinitrotoluene for 13 weeks at a low dose of 34 mg/kg per day in males and 38 mg/kg per day in females caused depressed weight gain. The middle dose of 93 and 108 mg/kg per day, respectively, was toxic, caused reticulocytosis and splenic hemosiderosis, and decreased spermatogenesis. The high dose of 266 and 145 mg/kg per day, respectively, was more toxic and lethal. Some rats had widespread and stiff-legged gaits and demyelination in the cerebellum and brain stem. After feeding up to 2 years, the low dose (0.57 and 0.71 mg/kg per day, respectively) caused no apparent toxic effects. The middle dose (3.9 and 5.1 mg/kg per day, respectively) was toxic; the high dose (34 and 45 mg/kg per day) was more toxic and shortened the life span. Target organs included the blood (toxic anemia), the liver (hepatocellular carcinoma), the testis (atrophy and depression of spermatogenesis), the connective tissue in males (fibromas), the mammary tissue in females (fibroadenomas), and the neuromuscular system in some rats.

Torsion and the Contralateral Testicle

The histologic effect of unilateral torsion on the contralateral testicle in adult Noble rats was examined. Utilizing detorsion or orchiectomy at 3 hours and 24 hours after torsion, the effect of early and late treatment of these changes was reviewed. The histologic changes consisted of loss of tubular spermatozoa, clumping of chromatin within the spermatocytes, the presence of Sertoli-only cells, evacuolization of Sertoli cytoplasm and germinal epithelial sloughing. Depression of spermatogenesis and decrease in the mean seminiferous tubular size was seen in the “normal” testicle after unilateral torsion. This effect was negated by early treatment with either orchiectomy or detorsion. Late detorsion does not negate these effects and late orchiectomy only partially negates them. Despite the depressed tubular function, the presence of early spermatogenic elements seen in the majority of the tubules in the “normal” testicle implies the possible reversibility of these changes.

Return of Fertility After Treatment for Nonseminomatous Testicular Cancer: Changing Concepts

We studied the return of ejaculation in 31 patients who had undergone retroperitoneal lymphadenectomy for stage I or II nonseminomatous germ cell testicular cancer. Ejaculation returned spontaneously in 13 patients and was restored by sympathomimetic drugs in 5 of 8 patients treated. Both patients known to have tried to father a child succeeded. We also studied the effects of chemotherapy (vinblastine and bleomycin with or without cisplatin) in 34 patients, 24 of whom also had undergone retroperitoneal lymphadenectomy. Although chemotherapy profoundly depressed spermatogenesis during treatment 75 per cent of the patients tested 18 months or more after completion of treatment had some return of function, as evidenced by normal follicle-stimulating hormone levels and/or the presence of live sperm in the ejaculate. We concluded that it is possible to perform a therapeutically sound retroperitoneal lymphadenectomy for low stage nonseminomatous testicular cancer that permits return of ejaculation in many patients and that spermatogenesis recovers in a significant number of patients treated for this cancer with modern chemotherapy. Thus, traditional beliefs that operative and drug treatment of nonseminomatous testicular cancer invariably causes infertility must be revised.

Toxicological Effects of Chlorine Dioxide, Chlorite and Chlorate

Review of the available literature obtained from both acute and chronic experiments utilizing rats, mice and chickens treated with ClO2, ClO2- and ClO3-in drinking water has demonstrated alterations in hematologic parameters in all species tested. The effects were usually dose related and marked changes occurred only at the higher dosages (up to 1000 mg/l.). In chronic studies, rats have been given ClO2 at doses of up to 1000 mg/l., and NaClO2 or NaClO3 at up to 100 mg/l., in their drinking water for one year. Treatment groups receiving ClO2, ClO2- or ClO3- showed alterations in erythrocyte morphology and osmotic fragility; at higher dosages mild hemolytic anemia occurred. An examination of blood glutathione content and RBC enzymes involving glutathione formation showed a dose-related diminution of glutathione in chlorine compound treated groups. The higher oxidative capacity of the chlorine compounds resulting in the decreased erythrocytic glutathione might well be the principal biochemical event leading to the other hematological alterations. More recent data show that ClO2, ClO2- and ClO3- alter the incorporation of 3H-thymidine into the nuclei of various organs of the rat. These data suggest the possibility of increased turnover cells of the gastrointestinal mucosa and inhibited DNA synthesis in several organs. In the latter category, most concern revolves around whether or not the apparent depression of DNA synthesis in the testes is associated with depressed spermatogenesis and reproductive toxicity in the male rat.

Toxicological effects of chlorine dioxide, chlorite and chlorate.

Review of the available literature obtained from both acute and chronic experiments utilizing rats, mice and chickens treated with ClO2, ClO2- and ClO3-in drinking water has demonstrated alterations in hematologic parameters in all species tested. The effects were usually dose related and marked changes occurred only at the higher dosages (up to 1000 mg/l.). In chronic studies, rats have been given ClO2 at doses of up to 1000 mg/l., and NaClO2 or NaClO3 at up to 100 mg/l., in their drinking water for one year. Treatment groups receiving ClO2, ClO2- or ClO3- showed alterations in erythrocyte morphology and osmotic fragility; at higher dosages mild hemolytic anemia occurred. An examination of blood glutathione content and RBC enzymes involving glutathione formation showed a dose-related diminution of glutathione in chlorine compound treated groups. The higher oxidative capacity of the chlorine compounds resulting in the decreased erythrocytic glutathione might well be the principal biochemical event leading to the other hematological alterations. More recent data show that ClO2, ClO2- and ClO3- alter the incorporation of 3H-thymidine into the nuclei of various organs of the rat. These data suggest the possibility of increased turnover cells of the gastrointestinal mucosa and inhibited DNA synthesis in several organs. In the latter category, most concern revolves around whether or not the apparent depression of DNA synthesis in the testes is associated with depressed spermatogenesis and reproductive toxicity in the male rat.

Cytogenetic and histological studies of testicular biopsies from subfertile men with chromosome anomaly.

Testicular biopsies from eight men with abnormal karyotypes have been examined for histological and cytogenetic evidence of disturbances of meiosis. Quantitative analysis of this material showed one, with a 13;14 Robertsonian translocation, to have apparently normal spermatogenesis. Three patients, one with a 47,XYY and two with 45,XY, inv 9 karyotypes, had an overall depression of spermatogenesis. Four others, all with major chromosomal abnormalities, had apparently normal spermatogenesis until the primary spermatocyte stage. Two of these had sex autosomal translocations. One, 45,Y,t(X;21), had a complete block at MI, the other, 46,X,t(Y;16), had a partial block at spermatid formation. One man with a reciprocal 2;10 translocation showed delay at all stages beyond spermatocyte formation and one man with an inversion of chromosome 3 showed impaired spermatid maturation.