Indenopyridine Hydrochloride Induced Testicular Spermatogenesis Failure with High Seminal Alkaline Phosphatase Levels in Male Dog.

Chang, Ching‐Cheng; Fung, Hang-Poung; Lin, Yi; Kuo, Ching-Yang; Chien, Chi-Wei

doi:10.1248/bpb.25.1097

Cited by 14 publications

(13 citation statements)

References 8 publications

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“…In contrast, CDB-4022 did not affect Leydig cell morphology or function. Serum testosterone levels were not altered by CDB-4022 treatment, there were no detectable effects on the androgendependent accessory sex organs, and animals exhibited normal libidos (1,2,4,6,7,9). These observations, in combination with the lack of genetic or overt toxicity, and other adverse side effects of indenopyridine analogs (1,2,11), indicate that these antispermatogenic compounds may have utility as male contraceptives.…”

mentioning

confidence: 86%

“…I NDENOPYRIDINES, INCLUDING CDB-4022, have been shown to possess antispermatogenic activity in rats, mice, and dogs (1)(2)(3)(4)(5)(6)(7)(8)(9). The indenopyridine, CDB-4022, induces infertility in adult male rats; however, this antispermatogenic effect appears to be irreversible unless endogenous testosterone production is suppressed by GnRH agonist or antagonist treatments before administration of CDB-4022 (7,9).…”

mentioning

confidence: 99%

“…The indenopyridine, CDB-4022, induces infertility in adult male rats; however, this antispermatogenic effect appears to be irreversible unless endogenous testosterone production is suppressed by GnRH agonist or antagonist treatments before administration of CDB-4022 (7,9). In contrast, other indenopyridine analogs have been shown to induce reversible infertility in mice, rats, and dogs (1,2,4,6). Differences in reversible vs. irreversible infertility may be related to differences in the potency of indenopyridine analogs, the dosing regimen used, the dose itself, and/or the species used for testing.…”

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confidence: 99%

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Development ofl-CDB-4022 as a Nonsteroidal Male Oral Contraceptive: Induction and Recovery from Severe Oligospermia in the Adult Male Cynomolgus Monkey (Macaca fascicularis)

et al. 2007

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The present study was undertaken to examine the antispermatogenic effect of l-CDB-4022 in the adult male cynomolgus monkey. Monkeys (four per group) were dosed via nasogastric tube for 7 d with l-CDB-4022 at 12.5 mg/kg.d or vehicle (d 0=first day of dosing). Plasma levels of l-CDB-4022 and its deesterified metabolite were nondetectable prior to treatment and in all vehicle-treated monkeys. Peak levels of l-CDB-4022 and its metabolite were observed at 4 h after dosing with steady-state levels apparent around d 4. Sperm concentration and total sperm per ejaculate were decreased to levels below 1x10(6) sperm/ml or sperm/ejaculate in l-CDB-4022-treated monkeys by d 17 and remained suppressed through wk 6. Sperm motility also declined to 0% for 6 wk. Testicular volume was reduced in l-CDB-4022-treated monkeys through d 21. The left testis and epididymis were removed from all monkeys on d 24. At this time, the most mature germ cells in the seminiferous tubules of testes from l-CDB-4022-treated monkeys were either spermatocytes or round spermatids. Immature germ cells, but not mature sperm, were found in the efferent ducts and collapsed epididymal lumen of l-CDB-4022-treated monkeys. A steady recovery in sperm motility, concentration, and total sperm per ejaculate was observed in l-CDB-4022-treated monkeys such that these parameters were not different from those of vehicle-treated monkeys by wk 16. Volume of the remaining testis increased in vehicle- and l-CDB-4022-treated monkeys after hemicastration; however, the increase in l-CDB-4022-treated monkeys was delayed compared with that observed in the vehicle-treated monkeys. The morphology of the remaining testis and epididymis, which were removed on wk 17, was normal. Serum inhibin B levels were increased in l-CDB-4022-treated monkeys during the dosing interval; thereafter serum inhibin B levels declined such that there was no difference between the groups by wk 3. l-CDB-4022 treatment did not affect circulating levels of testosterone, LH, FSH, or estradiol. In conclusion, these data indicate that in the cynomolgus monkey, a representative higher primate, l-CDB-4022 exerts a selective antispermatogenic action, which was reversible under the conditions of this study and thus has potential as a nonhormonal oral male contraceptive.

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confidence: 86%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Development ofl-CDB-4022 as a Nonsteroidal Male Oral Contraceptive: Induction and Recovery from Severe Oligospermia in the Adult Male Cynomolgus Monkey (Macaca fascicularis)

et al. 2007

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“…The SMI did not differ among samples obtained from different parts of the testes, confirming that germ cell development is fairly synchronous throughout the testes of European eels (Miura et al 1991a;Miura and Miura 2001). The application of area fractions to estimate the prevalence of different categories of germ cells should eliminate potential bias that may arise from differences in the orientation of the tissue in histological sections (e.g., Chang et al 2002;Neuenhagen et al 2007). The independence of the SMI in relation to sectioning angle and magnification level is contrasted by the significant differences in SMI among weeks, indicating the capabilities of the method.…”

Section: Applicability Of the Spermatogenic Maturity Indexmentioning

confidence: 70%

Assessment of Testis Development during Induced Spermatogenesis in the European Eel Anguilla anguilla

2011

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In a study of reproduction in male European eels Anguilla anguilla, we induced spermatogenesis through hormone injection and established a spermatogenic maturity index (SMI) as a novel quantification of testis development. Eels in the experiments were sacrificed weekly and testis tissue was sampled for histological analysis of spermatogenesis. Testis development was followed over 18 weeks, during which the males continued to develop spermatocytes and produce spermatozoa. The SMI describes testis development from estimation of the area fractions of various tissue categories characterized by progressive gamete development stages in histological sections of the testes. The index weighs the volume fractions of the different tissues (somatic cells and germ cell stages) and describes development on a scale of 0 to 1. The method improves the existing histological classification, providing a quantitative measure that reflects the spermatogenic process and can be correlated with morphological and physiological parameters. In this study, the SMI reacted immediately to the onset of spermatogenesis and increased linearly over time, tracking the development of spermatocysts and spermatozoa. In week 7, the SMI reached a stable level of around 0.75, where it remained, with limited fluctuations, until the end of the experiment. This reflected the composition of different germ cell stages in the testis tissue with a continuous generation of spermatocysts and production of spermatozoa. In comparison, the gonadosomatic index showed a delayed response to the onset of spermatogenesis and fluctuated substantially during the sperm production period. The properties of the SMI made it a useful index for describing spermatogenesis in male European eels during this experiment and a promising tool for quantifying testis development and describing male reproductive strategy in other fish species.

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“…When administered in ground meat daily to gray wolves it suppressed spermatogenesis without affecting mating behavior (Asa et al 1996). Indenopyridine also blocks sperm production; it has been tested in rodents and dogs (Chang et al 2002). Alpha-chlorohydrin (Epibloc), a male chemosterilant, was approved by the Environmental Protection Agency (EPA) for use as a rat control agent in 1982 (Bowerman & Brooks 1971;Ericsson 1982;Andrews & Belknap 1983) but is no longer marketed.…”

Section: Steroids/hormonesmentioning

confidence: 99%

Review of issues concerning the use of reproductive inhibitors, with particular emphasis on resolving human‐wildlife conflicts in North America

Fagerstone

Miller

Killian

et al. 2010

Integrative Zoology

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Indenopyridine Hydrochloride Induced Testicular Spermatogenesis Failure with High Seminal Alkaline Phosphatase Levels in Male Dog.

Cited by 14 publications

References 8 publications

Development ofl-CDB-4022 as a Nonsteroidal Male Oral Contraceptive: Induction and Recovery from Severe Oligospermia in the Adult Male Cynomolgus Monkey (Macaca fascicularis)

Development ofl-CDB-4022 as a Nonsteroidal Male Oral Contraceptive: Induction and Recovery from Severe Oligospermia in the Adult Male Cynomolgus Monkey (Macaca fascicularis)

Assessment of Testis Development during Induced Spermatogenesis in the European Eel Anguilla anguilla

Review of issues concerning the use of reproductive inhibitors, with particular emphasis on resolving human‐wildlife conflicts in North America

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