Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulfogalactosylglycerolipid (SGG) is the major mammalian male germ cell glycolipid and has been implicated in sperm/egg binding. Mycoplasma pulmonis, a species of Mollicutes, is associated with male infertility in rodents. Purified SGG incubated in the presence of M. pulmonis was enzymatically degraded by both desulfation and deacylation. Desulfation occurred primarily at alkaline pH, and deacylation also increased with increased pH, indicating that these represent novel enzymatic activities. Digestion was facilitated, but not dependent on, the presence of detergent. Rat spermatozoa exposed to M. pulmonis showed a reduction in SGG content which was particularly marked for cauda (mature) spermatozoa. With the aid of tlc overlay binding procedure, intact M. pulmonis were found to bind specifically to sulfated glycolipids and thus SGG may provide the cell membrane receptor for this organism. The topology of mycoplasma binding to rat sperm was consistent with the known topology of sperm SGG. The reduced binding (and subsequent digestion) of caput spermatozoan SGG correlates with the membrane colocalization of SGG and its endogenous binding protein at this stage. Separation of SGG and its binding protein during epididymal sperm maturation appears to facilitate M. pulmonis binding to and digestion of cauda sperm SGG. The binding and degradation of the sperm SGG by M. pulmonis may play a role in the induction of infertility which follows infection with these organisms by interfering in sperm/egg receptor recognition.
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PMID:Male germ cell specific sulfogalactoglycerolipid is recognized and degraded by mycoplasmas associated with male infertility. 229 20

Pyrimethamine's antifertility effects in the male mouse suggest that this agent has potential as a male contraceptive. This dihydrofolate reductase inhibitor was administered to 72 adult male Swiss-Webster mice over a 50-day period at dosages ranging from 10-200 mg/kg/day. During the last 10 days of drug administration, the study mice were exposed to 3 female mice who underwent 2 reproductive cycles. The female mice were examined for gravidity 19 days after the onset of the breeding cycle. Male infertility was dose-dependent, with no pregnancies occurring among the partners of mice who received the maximum dosage of pyrimethamine. Also inversely proportional to dosage were the number and motility of epididymal sperm in the treated mice and mean seminiferous tubule diameter and testicular and epididymal weights. Time course analysis revealed that the drug begins to exert its antifertility effect 33 days after administration and nearly complete infertility is achieved with 50 days, suggesting that pyrimethamine acts on early-midspermatogenesis. All mice returned to normal fertility status 44 days after treatment ended, and epididymal sperm reserves, sperm motility, and testicular and epididymal weights also returned to baseline values within this time period. Of particular interest was the finding that when pyrimethamine was administered to another group of mice for 80 days, infertility was significantly reduced beyond that achieved in 50 days, yet there were no further effects on testicular epididymal function. It would appear that pyrimethamine's mechanism of action is its antifolate action, with the main effect occurring on the testes rather than the epididymis.
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PMID:Pyrimethamine: an approach to the development of a male contraceptive. 230 8

This paper compares the statistical precision and biological sensitivity of multiple indices of reproductive function to infertility in the male rodent. The studies discussed include those that examined reproductive function in the male following perinatal exposure to reproductive toxicants and others in which the compounds were administered to young-adult males, often with very diverse results. For example, some chemicals that alter sex differentiation reduce fertility by affecting breeding performance alone (polychlorinated biphenyls (PCBs), fenarimol, or losulazine), without altering sperm and testicular measures. Others also markedly alter sex differentiation of the genitalia, the accessory glands and the testis in addition to their effects on central nervous system (CNS) sex differentiation and mating behavior (testosterone, flutamide, cyproterone acetate, tamoxifen, estradiol and diethylstilbestrol (DES)). In contrast, prenatal exposure to compounds that alter primary germ cell survival (busulphan, congo red) induce partial gonadal/germ cell agenesis without altering sex differentiation. These chemicals dramatically reduce testicular sperm production in the male offspring, and the most severely affected males are infertile. In a series of studies conducted in our laboratory, young male rats were exposed to known reproductive toxicants in a dose related manner from puberty, through young adulthood and breeding. We have found that the profile of effects varies considerably depending upon the chemical's mechanism of toxicity. When a compound produced infertility through direct effects of testicular function (Carbendazim (MBC) and dibutyl phthalate (DBP)), then testis weight, testicular histology, and testicular sperm head counts provided sensitive indicators of toxicity. In general, dramatic reductions in sperm production are required to induce infertility and these changes were accompanied by elevated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and changes in human chorionic gonadotropin (hCG)-stimulated testosterone synthesis. Chemicals that have hormonal activity, alter the internal endocrine environment, or directly effect CNS function induce a completely different profile of effects. For example, estrogen administration alters the function of the seminal vesicle and the endocrine system, and reduces epididymal sperm reserves; while testicular measures are relatively unaffected. Since very different spectrums of effects are produced by different compounds, no single endpoint will consistently be the most sensitive indicator of reproductive toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Correlation of sperm and endocrine measures with reproductive success in rodents. 266 89

Given the observation that naturally occurring antibodies to eggs and sperm can cause infertility, it seems feasible to pursue development of an infertility vaccine based on the induction of a specific immune response to gamete or early embryo antigens. Antibodies directed to the zona pellucida have been researched, but at current levels of purification, result in reduced ovarian hormone production. Of the numerous sperm antigens, LDH-C4 appears most promising for use in a vaccine. In the past decade, antisperm antibody investigations have focused on surface antibodies and sperm mixed agglutination reactions. It appears that antibodies in accessory fluids bind to sperm during ejaculation and/or antisperm antibodies enter the male tract at the epididymal level or higher. Antibodies directed against egg or sperm may prevent or modify the normal process of capacitation in which sperm undergo a series of biochemical and morphological transformations. Antisperm antibodies can suppress fertility by preventing sperm transport through cervical mucus or impeding the sperm-egg interaction during fertilization. The definition of sperm antigens associated with infertility--essential for development of a contraceptive vaccine--is being facilitated by monoclonal antibody techniques and DNA technology. Since the sperm surface is organized into highly specialized and distinct regions, cell recognition is an important research area. Most salient to the recognition and regulation of cell interaction are the components of the sperm plasma membrane and the zona pellucida.
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PMID:Natural and induced immunological infertility. 267 49

Based on their own experience with 83 reconstructive microsurgeries performed for epididymis obstruction the authors concluded that a simple incorporation of microsurgical techniques into the surgery of excretory infertility failed to substantially improve the results of the treatment. Supposing a well-managed clinical study to be the main tool to provide better results and the data of animal studies to be inapplicable for the diseases of the human reproductive system, the authors suggested that the aforementioned study in the clinical settings should conform to the two major requirements: an uniform pattern of the techniques employed and an exacting control over anastomosis application. As a method of choice, end-to-side vasoepididymostomy was offered. A training model for gaining the mastery of epididymis microsurgery techniques was developed as well. The reliability of the method was proved by experiments on 20 rabbits. 17 animals gave offsprings. The system of epididymal ducts studied in health opened the possibility of a well-founded division of epididymis into zones of surgical importance.
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PMID:[Microsurgery of the appendix testis (experimental research)]. 269 67

Immunological techniques have enabled us to see that mammalian sperm undergo complex surface changes during maturation in the male reproductive tract. Binding affinity and sperm surface binding domains have been demonstrated using immunocytochemical technique. Recent studies using monoclonal antibodies suggest that these highly specific probes are useful for detecting changes in the sperm surface during epididymal transit and in defining the role of these complex changes in sperm maturation and the process of fertilization. Studies involving immunological mapping of the sperm surface, in parallel with immunohistological and functional inhibition test, have provided important information concerning the role of individual sperm antigens in fertility. A better understanding of local antibody production and cell-mediated immune responses in the male reproductive tract has also led to the understanding of immunological infertility. Sperm membrane is comprised of multiple domains each of which is sharply demarcated, with a unique composition and physiological role.
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PMID:Immunocytochemistry of male reproductive organs. 269 93

Rats were treated with a single high dose of methoxy acetic acid (MAA; 650 mg/kg) specifically to deplete seminiferous tubules of pachytene and later spermatocytes. The impact of this selective depletion on subsequent spermatogenesis, sperm output and fertility was then evaluated at intervals ranging from 3 days to 10 weeks. Cauda epididymal sperm number was reduced progressively beyond 2 weeks post-treatment and reached a nadir at 5-6 weeks (28-34% of control values) before recovering progressively back to control levels at 10 weeks. Sperm motility was reduced significantly at 4-7 weeks post-treatment with a nadir at 6 weeks (35% of control values). Thus, at 5-6 weeks after MAA treatment, motile sperm output was reduced by 82-88%. Despite these changes, there was little evidence for infertility in the majority of treated males during a serial mating trial. Evaluation of seminiferous tubule morphology combined with germ cell counts at stage VII of the spermatogenic cycle confirmed that, initially, MAA induced the specific loss of pachytene and later spermatocytes at all stages other than early to mid stage VII. Maturation depletion of germ cells at later intervals was consistent with the initial effects of MAA, although at 21 days post-treatment a number of unpredicted (? secondary) changes in spermatogenesis were observed. These were (a) a reduction in number of pachytene spermatocytes at late stage VII/early stage VIII, (b) retention of sperm at stages IX-XIV, and (c) increased degeneration of pachytene spermatocytes and round spermatids at stage VII and of secondary spermatocytes at stages XIV-I. Whilst none of these changes was severe, together they probably accounted for the unexpectedly prolonged drop in sperm output. It is concluded that whilst deleterious changes in spermatogenesis may occur secondarily following MAA treatment, for the most part spermatogenesis proceeds normally and fertility is largely maintained despite a massive but transient decrease in sperm output.
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PMID:Evaluation of the effect of selective germ cell depletion on subsequent spermatogenesis and fertility in the rat. 271 72

Failure of epididymal spermatozoa from T/t mutant mice, but not from t/t individuals, to fertilize oocytes in vitro was partially overcome by opening a small aperture in the zona pellucida with acidified Tyrode's solution to permit direct access of the spermatozoon to the vitellus. This study provides a model system to evaluate requirements for successful zona drilling in the treatment of human infertility and further insights into the effects of the t complex on sperm fertility.
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PMID:Failure of spermatozoa from T/t mice to fertilize in vitro is overcome by zona drilling. 272 19

The reproductive toxicology of metronidazole was studied in rats. Male Charles River Crl:CD(SD)BR rats (10/group) were treated with metronidazole as a dietary admixture at doses of 0 (control), 25, 100, and 400 mg/kg/day for 8 weeks. The reversibility of effects after a 3 1/2-month recovery period was determined in separate groups of 10 control and 10 rats treated with 400 mg/kg/day of metronidazole. After 2 and 4 weeks of metronidazole treatment, mating performance and fertility in treated and control animals were comparable. After 6 weeks of treatment, all high-dose rats were infertile; however, fertility in low- and middose rats was not affected. High-dose male rats killed after 8 weeks of treatment showed markedly decreased testicular and epididymal weights, and markedly decreased testicular spermatid counts and epididymal sperm counts. Most of the few epididymal sperm present in high-dose rats were viable, but morphologically abnormal. Histologically, severe degeneration of the seminiferous epithelium was observed in the testes of high-dose rats; the tubules were generally devoid of primary or secondary spermatocytes and spermatids. Rats treated with the low and middle doses of metronidazole exhibited normal testicular and epididymal weights, and normal testicular spermatid counts and epididymal sperm reserves. Epididymal sperm viability and morphology of treated and control animals were comparable. Minimal histologic changes were observed in the testes of middose rats, including degenerative fragmentation of spermatozoa and spermatids. In high-dose recovery rats, fertility was restored in most rats by 8 weeks after the cessation of treatment; however, the testicular and epididymal weights and sperm counts of rats killed after 3 1/2 months of recovery had increased but were still significantly decreased in treated rats as compared with controls. Histologically, spermatogenesis was observed in most tubules; however, a portion of atrophic tubules persisted. It is concluded that high doses of metronidazole produce infertility in the male rat through inhibition of spermatogenesis as early as the stage of the primary spermatocyte. This effect is partially reversible.
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PMID:Effect of metronidazole on fertility and testicular function in male rats. 273 55

Surgery for male obstructive infertility is not always successful. A number of clinical and operative findings, not previously reported, may influence the outcome. We have studied 182 patients with azoospermia who underwent vasoepididymostomy. The pre-operative and operative findings which adversely affected the function of the anastomosis were identified. The presence of spermatozoa in the semen sample was taken to mean a successful anastomosis. Abnormal testicular histology was an adverse pre-operative finding. Adverse operative findings included non-canalisation of the epididymal tubules and hypoplasia of the epididymis; both factors were associated with a high failure rate (almost 100%). The anastomosis was a failure in 78% of the patients when no fluid was seen on sectioning the epididymis. In the absence of adverse findings the success rate of vasoepididymostomy was 59%. Pre-operative testicular biopsy, together with careful observation and recording of findings before and during surgery, are recommended to avoid needless exploration and anastomosis.
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PMID:Prognostic factors in the surgical treatment of azoospermia. 276 72


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