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PubMed1989

Nonhormonal mediation of male reproductive tract damage: data from contraceptive drug research.

Chemicals can interfere with hormonal control of the male reproductive tract and/or directly alter male reproductive tract function. A review is presented of those chemicals developed and tested as male contraceptive agents which have a direct effect on the male reproductive tract with minimal disturbance of the hormonal milieu. Such chemicals can have one or more sites of action: 1) the testis, disturbing spermatogenesis; 2) the epididymis, altering sperm maturation; 3) the vas deferens, affecting sperm transport; and 4) the accessory sex glands, entering the ejaculate and changing the functional activity of the spermatozoa. Examples of each mode of action are presented.

Animals↗
PubMed1983

Effects of low doses of alpha chlorohydrin on the lipid metabolism of the rat testis and epididymis--a correlative histochemical and biochemical study.

A biochemical and histochemical study was carried out on the effects of low doses of alpha chlorohydrin on the lipid metabolism of the rat testis and epididymis. Administration of alpha chlorohydrin in low doses (6.5 mg/kg for 9 days) to Wistar strain rats caused an elevation of lipid levels in the testis and epididymis. Actually, an increase in the neutral fat occurred with a corresponding decrease in the phospholipids after treatment with alpha chlorohydrin. We suggest that the rat's total lipid, total cholesterol, cholesterol esters, and triglycerides were increased at the cost of phospholipids. The altered levels of lipid fractions were due to the increased activity of glycerol phosphate dehydrogenase and to the decreased activities of nonspecific esterase and lipase after treatment with the drug. These alterations of lipid metabolism, which were regulated through their enzyme systems, strongly reflect the damage to the metabolism of the testis and epididymis after treatment with low doses of alpha chlorohydrin, although there was no histological damage at this dose level.

Animals↗
PubMed1980

The epididymal microenvironment: a site of attack for a male contraceptive?

During their development, spermatozoa are continually bathed in fluid provided by epithelial secretions of the seminiferous tubule and the epididymal duct. This fluid or microenvironment is probably very important for spermatozoal maturation and survival. Micropuncture and microanalytic studies have revealed the occurrence of several biochemical changes of this specialized microenvironment along the epididymal duct; these changes seem to be linked to sperm maturation. The interactions between maturing spermatozoa and their microenvironment must be understood before interference in sperm maturation through intervention of the formation of the microenvironment is possible. Several compounds have been shown to interfere in spermatozoal maturation in the epididymis although their use as male contraceptives requires further investigation.

Animals↗
PubMed1981

Carcinogenicity tests of certain environmental and industrial chemicals.

Fourteen chemicals of varied uses were tested for carcinogenicity by oral administration in male and female Charles River CD rats. Under the conditions of the tests, propane sultone, propylene imine, and ethylenethiourea, in addition to the positive control N-2-fluorenylacetamide, were carcinogenic. Avadex, bis(2-chloroethyl) ether, the potassium salt of bis(2-hydroxyethyl) dithiocarbamic acid, ethylene carbonate, and semicarbazide hydrochloride were not carcinogenic under the test conditions. Dithiooxamide, glycerol alpha-monochlorohydrin, and thiosemicarbazide gave somewhat ambiguous results, though administered at high enough dose levels to be toxic. An inadequate number of animals survived treatments with sodium azide, sodium bisulfide, and vinylene carbonate, or the animals may not have received sufficiently high doses of the test chemicals to provide maximum test sensitivity. However, there were no indications that these three chemicals were carcinogenic under the test conditions.

2-Acetylaminofluorene↗
PubMed1994

Liver injury induced by dichloropropanols--changes in the time course on hematological and blood chemical examinations.

The toxicity of dichloropropanols (DCPs) was investigated by hematological and blood chemical examination. Solutions of two isomers of DCPs, 1,3-dichloro-2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at a concentration of 100 mg/ml and 0.1 ml of each was subcutaneously injected into male Wistar rats weighing about 200 g. Acute changes on transaminases and number of platelets were determined in the time course. 6 hours later, transaminases showed significant increases while the number of platelets significantly decreased in the DC2P-treated group. In the half the of DC2P-treated group, transaminases had increased furthermore at 24 hours, while those in the rest were recovered to the control level. No changes were observed in the DC1P-treated group. These results indicate that there is a prominent hepatotoxicity in DC2P, with the individual diversities to some extent and the hepatic toxicity differs considerably between DC2P and DC1P. Therefore, the monitoring of the working environment and biological monitoring of DCPs should be mandatory, in the workplace where DCPs, especially DC2P, are utilized.

Alanine Transaminase↗
PubMed1976

Target sites for suppressing fertility in the male.

The present status and perspectives in the control of fertility in the male have been reviewed. There are two potential sites in the male reproductive processes that can be used as targets for regulation of fertility in the male: (1) inhibition of spermatogenesis, and (2) interference with sperm maturation in the epididymis. A variety of compounds tested for their antispermatogenic action in laboratory animals have no future for the control of fertility in the human male because of a number of undesirable side effects (cf. Prasad, 1973). Progestational compounds inhibit spermatogenesis by affecting the hypothalamo-hypophysial system and result in impairment of libido. The possibility of adjustment of the minimal dose of progestational compounds required to induce suppression of spermatogenesis and reduction of plasma testosterone to a level compatible with the maintenance of normalcy of libido and potency needs to be studied. A new approach to contraception in the male involves the use of a combination of progestational compounds for suppression of spermatogenesis along with testosterone (administered through silastic capsule implants or as intramuscular injections) for maintenance of libido and accessory sex gland function. A number of such combinations have been tested clinically with some success. However, the limitations of side effects, such as weight gain, gynecomastia, and psychological complications preclude their long-term use for contraception in man. Short-term use of these combination regimens by the male for 1 year followed by use of a contraceptive method by the female may be desirable to encourage partnership in family planning. Although testosterone and other androgens suppress spermatogenesis in man, the feasibility of their use for contraception depends on the establishment of a dosage and mode of adminstration that provide antispermatogenic action without causing more general metabolic alterations. Inhibition of spermatogenesis by selective interference with the action of FSH on the Sertoli cells by active or passive immunization or by selective suppression of synthesis and release of FSH by administration of "Inhibin" offers exciting possibilities in the control of fertility in the male. Studies on the physiology of the rete testis highlight its importance as a post-tubular site of action of antifertility agents in conveying (to the epididymis) compounds interfering with epididymal functions and/or viability of spermatozoa. A new approach to the induction of functional sterility in the male by selective alteration of epididymal function by a local androgen deprivation effect has been successfully tested in clinical trials. Small doses of cyproterone acetate, administered orally, result in maintenance of libido and accessory sex gland function accompanied by a decrease in the motility of ejaculated spermatozoa and incomplete inhibition of spermatogenesis...

Androgen Antagonists↗
PubMed1976

Mechanism of action of alpha-chlorhydrin on the testes and caput epididymidis of rat, gerbil (Meriones hurrianae), bat and mouse.

Chronic administration of alpha-chlorhydrin caused lesions of rat, gerbil and bat testicles selectively. The seminiferous epithelium became systematically depleted of spermatogenic elements. alpha-Chlorhydrin did not produce lesion of the caput epididymidis. Sloughing of the epithelial lining did not occur. No obstruction of the lumen of the epididymal duct was seen. The growth of androgen-dependent organs, i.e. seminal vesicles, epididymis and levator ani muscles was suppressed. alpha-Chlorhydrin caused no response directly on the epididymides. Subcutaneous or oral administration of alpha-chlorhydrin for a period of 3-5 weeks caused no response in the testes and epididymides of the mouse.

Administration, Oral↗
PubMed1976

Observations on the effects of alpha-chlorhydrin on the testes and pituitary gonadotrophs of gerbil (Meriones hurrianae) and rat.

(1) Lower doses of alpha-chlorhydrin caused high selectivity of lesions in the seminiferous tubule of rat and gerbil. (2) The seminiferous epithelium became systematically depleted of spermatogonia, spermatocytes, spermatids and finally spermatozoa in this sequence. (3) The suppression of RNA concentration in the testes and seminal vesicle is conspicuous. (4) The growth of androgen-dependent organs, i.e. seminal vesicles, ventral prostate, epididymes and perineal complex, is suppressed. (5) These effects are reversible. Repopulation of testis tubules occurs followed by a 40-day recovery period in rat and gerbil. (6) alpha-Chlorhydrin administration brings about hypertrophy of pituitary gonadotrophs which is also reflected in the increased basophilic cell percentage (control: 15.5% alpha-chlorhydrin: 21.5%; p less than 0.01).

Animals↗