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)

The introduction of microsurgical techniques has revolutionized the treatment of male infertility. As a result of technical advances and innovation over the past 10-15 years, previously infertile couples are now able to conceive naturally or to parent their own biological children with the aid of assisted reproductive technologies. This article reviews the indications, techniques, and outcomes of the various microsurgical procedures currently used to optimize male fertility. The most up-to-date methods of microsurgical vasal and epididymal reconstruction, sperm retrieval, and varicocele repair are discussed.
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PMID:Microsurgical management of male infertility. 1683 26

The roles of the leucine-rich repeat domain containing G protein-coupled receptor (GPCR) 4 (Lgr4), which is one of the orphan GPCRs, were analyzed with the Lgr4 hypomorphic mutant mouse line (Lgr4(Gt)). This homozygous mutant had only one-tenth the normal transcription level; furthermore, 60% of them survived to adulthood. The homozygous male was infertile, showing morphologic abnormalities in both the testes and the epididymides. In the testes, luminal swelling, loss of germinal epithelium in the seminiferous tubules, and rete testis dilation were observed. Cauda epididymidis sperm were immotile. Rete testis dilation was due to a water reabsorption failure caused by a decreased expression of an estrogen receptor (ESR1) and SLC9A3 in the efferent ducts. Although we found differential regulation of ESR1 expression in the efferent ducts and the epididymis, the role of ESR1 in the epididymis remains unclear. The epididymis contained short and dilated tubules and completely lacked its initial segment. In the caput region, we observed multilamination and distortion of the basement membranes (BMs) with an accumulation of laminin. Rupture of swollen epididymal ducts was observed, leading to an invasion of macrophages into the lumen. Male infertility was probably due to the combination of a developmental defect of the epididymis and the rupture of the epithelium resulting in the immotile spermatozoa. These results indicate that Lgr4 has pivotal roles to play in the regulation of ESR1 expression, the control of duct elongation through BM remodeling, and the regional differentiation of the caput epididymidis.
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PMID:LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice. 1707 37

Serine/threonine protein phosphatase 1 (PP1) consists of four ubiquitously expressed major isoforms, two of which, PP1gamma1 and PP1gamma2, are derived by alternative splicing of a single gene, Ppp1cc. PP1gamma2 is the most abundant isoform in the testis, and is a key regulator of sperm motility. Targeted disruption of the Ppp1cc gene causes male infertility in mice due to impaired spermiogenesis. This study was undertaken to determine the expression patterns of specific PP1 isoforms in testes of wild-type mice and to establish how the defects produced in Ppp1cc-null developing sperm are related to the loss of PP1gamma isoform expression. We observed that PP1gamma2 was prominently expressed in the cytoplasm of secondary spermatocytes and round spermatids as well as in elongating spermatids and testicular and epididymal spermatozoa, whereas its expression was weak or absent in spermatogonia, pachytene spermatocytes, and interstitial cells. In contrast, a high level of PP1gamma1 expression was observed in interstitial cells, whereas much weaker expression was observed in all stages of spermatogenesis. Another PP1 isoform, PP1alpha, was predominant in spermatogonia, pachytene spermatocytes, and interstitial cells. Examining the temporal expression of PP1 enzymes in testes revealed a striking postnatal increase in PP1gamma2 levels compared with other isoforms. Testicular sperm tails from Ppp1cc-null mice showed malformed mitochondrial sheaths and extra outer dense fibers in both the middle and principal pieces. These data suggest that in addition to its previously documented role in motility, PP1gamma2 is involved in sperm tail morphogenesis.
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PMID:Analysis of Ppp1cc-null mice suggests a role for PP1gamma2 in sperm morphogenesis. 1730 Dec 92

FKBP52 is a member of the FK506-binding family of immunophilins and serves as a co-chaperone for steroid hormone nuclear receptors to govern appropriate hormone action in target tissues. Male mice missing Fkbp52 are infertile, and this infertility has been ascribed to compromised sensitivity of the anterior prostate, external genitalia, and other accessory sex organs to androgen. Here, we show additional defects contributing to infertility. We found that epididymal Fkbp52(-/-) sperm are sparse often with aberrant morphology, and they have reduced fertilizing capacity. This phenotype, initially observed in null males on a C57BL/6/129 background, is also maintained on a CD1 background. Expression studies show that while FKBP52 and androgen receptor are co-expressed in similar cell types in the epididymis, FKBP52 is also present in epididymal sperm flagella. Collectively, our results suggest that reduced number and abnormal morphology contribute to compromised fertilizing capacity of Fkbp52(-/-) sperm. This study is clinically relevant because unraveling the role of immunophilin signaling in male fertility will help identify new targets for male contraceptives and/or alleviate male infertility.
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PMID:Deficiency of co-chaperone immunophilin FKBP52 compromises sperm fertilizing capacity. 1730 7

Methods routinely used to preserve mouse spermatozoa require that the male be killed to recover spermatozoa from the epididymides. Here we obtained multiple samples of ejaculated spermatozoa from normal fertile C57BL/6 and infertile Hook1/Hook1 (formerly known as azh/azh) mutant males from uteri after mating, thus avoiding termination of the males. Ejaculated sperm were preserved by conventional cryopreservation or by rapid freezing without cryoprotection, and were injected into the oocytes by intracytoplasmic sperm injection (ICSI). The proportions of oocytes that survived, became activated, and developed into two-cell embryos were similar when comparing the two preservation methods in wild-type versus Hook1/Hook1 mice and tested mice versus controls (fresh and rapid-frozen epididymal and fresh ejaculated sperm). Two-cell embryos were transferred into the oviducts of pseudopregnant females, and fetal development was examined at Day 15 of gestation. A total of 39%-54% of transferred embryos produced with preserved ejaculated sperm implanted. Live, normal fetuses (11%-17%) were obtained in all examined groups and from all males included in the study. More implants (71%-82%) and fetuses (28%-31%) were noted in controls. Lower developmental potentials of embryos produced with preserved ejaculated sperm might be due to their capacitation status; the majority of sperm retrieved from the uterus were capacitated. This study bears significance for the maintenance and distribution of novel mouse strains. The method is applicable for all types of mice, including those with male infertility syndromes. The sole requirement is that the male of interest is able to copulate and its ejaculate contains spermatozoa.
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PMID:Preservation of ejaculated mouse spermatozoa from fertile C57BL/6 and infertile Hook1/Hook1 mice collected from the uteri of mated females. 1731 12

This study aimed to examine the association between the interval from ejaculation to analysis and epididymal and accessory sex gland function in relation to sperm motility. Ejaculates from 1079 men assessed for infertility were analyzed according to World Health Organization guidelines. Biochemical markers were measured in semen to assess the function of the epididymis (neutral alpha-glucosidase [NAG]), prostate (prostate-specific antigen [PSA] and zinc), and seminal vesicles (fructose). Three groups were defined according to time from ejaculation to analysis: G(< or =30) (24-30 minutes), G(31-60) (31-60 minutes), and G(>60) (63-180 minutes). The proportion of progressively motile sperm was significantly lower in G(>60) than in G(< or =30) (mean difference, 8.0%; 95% confidence interval [CI], 2.0%-13%) or G(31-60) (mean difference, 6.0%; 95% CI, 1.0%-12%). The proportion of rapid progressive sperm motility was significantly higher in G(< or =30) compared with G(31-60) (mean difference, 3.0%; 95% CI, 1.0%-5.0%) and G(>60) (mean difference, 6.0%; 95% CI, 1.0%-10%). Sperm morphology and viability did not vary significantly between the groups. However, PSA levels in G(>60) were 29% and 31% significantly lower than in G(< or =30) (95% CI, 3.0%-54%) and G(31-60) (95% CI, 7.0%-58%), respectively. Moreover, men in G(>60) had 29% and 17% significantly lower zinc compared with those in G(< or =30) (95% CI, 4.0%-69%) and G(31-60) (95% CI, 4.0%-64%), respectively. Levels of NAG and fructose did not differ significantly between the groups. There were negative associations between the ejaculation-to-analysis interval and sperm motility and levels of PSA and zinc. In male infertility assessments, semen analysis should be performed within 60 minutes of ejaculation.
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PMID:Effects of ejaculation-to-analysis delay on levels of markers of epididymal and accessory sex gland functions and sperm motility. 1755 11

Spermatozoal maturation in the epididymis is dependent on proteins secreted by the epithelium and those that create the proper ionic composition and pH of the lumen as well as the blood-epididymal barrier. For the human epididymis, little information exists about the regulation of these proteins in male infertility. Our objectives were to assess gene expression profiles in the caput epididymidis from men with normal spermatogenesis and men with nonobstructive azoospermia. With microarrays, we identified 414 genes in the caput epididymidis that were differentially regulated in infertile men by at least 2-fold compared with the fertile men. They were mostly involved in transcription, intracellular signaling, immunity, and fertility. Although the expression of genes encoding tight junctional proteins was not affected, the localization of CLDN10 and TJP1, but not CLDNs 1, 3, and 8, was altered in infertile patients, suggesting that there are changes in the paracellular functions of the blood-epididymal barrier. Differentially regulated genes included several encoding proteins involved in spermatozoal maturation, water and ion channels, and beta-defensins: CRISP1, SPINLW1, FAM12B, and DEFB129 were upregulated, whereas CFTR, AQP5, KCNK4, KCNK17, SLC6A20, SLC13A3, DEFB126, and DEFB106A were downregulated. Furthermore, the immunolocalization of AQP5, but not of CFTR or CRISP1, varied in infertile and fertile patients. The observation that the expression of genes involved in water and ion transport were repressed in infertile patients suggests that these genes are regulated by the presence of testicular products or spermatozoa in the epididymal lumen or are part of a broader syndrome associated with nonobstructive azoospermia.
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PMID:Alterations in gene expression in the caput epididymides of nonobstructive azoospermic men. 1792 28

Varicocele is the abnormal dilation of venous pampiniform plexus and internal spermatic vein. Its prevalence in the adolescent period is almost equal to the prevalence of adult age. That is why the disease is accepted to appear in early adolescence and does not disappear spontaneously. Varicocele is established to be the most common cause of infertility in the adulthood period in terms of the testicular and/or epididymal damages it causes. Besides, malfunctioning of testis and/or epididymis cannot be blamed as the one and only reason of infertility. One major reason of the male infertility is vas deferens motility disorders. There is limited data in the literature investigating the effects of varicocele on the vas deferens motility. The aim of the study is to evaluate not only the motility defects of vas deferens for the period of varicocele, but also the effects of surgical varicocele correction on vas deferens motility. Thirty male Wistar-Albino rats were allocated to five groups. In the control group (Gr C, n = 6) bilateral vas deferens strips were harvested without any surgical intervention. Using the partial left renal vein obstruction technique, the experimental varicocele model was performed for the other four groups. Varicocele was apparent for these animals after the fourth week of the venous ligation. Bilateral vas deferens strips of varicocele group (Gr V, n = 6) were harvested. The rest of the animals having varicocele underwent relaparotomies. Three different surgical procedures were performed to these animals. The animals of group P (Gr P, n = 6) and group I (Gr I, n = 6) underwent Palomo and Ivanissevich procedures, respectively, for varicocele correction. And the animals of group S (Gr S, n = 6) underwent sham operation. After 4 weeks of relaparotomies, bilateral vas deferens strips of all three groups harvested. The electrical field stimulation (EFS) induced responses of all vas deferens strips as well as exogenous drug induced responses were recorded and analysed. The results of the study showed that the varicocele significantly inhibited the first phase of biphasic response of vas deferens in the ipsilateral side. However the correction of varicocele, free from surgical technique, ameliorated the affected first phase of EFS induced biphasic response in the ipsilateral side. The results of this study suggest that varicocele can be the reason of male infertility by not only causing testicular and/or epididymal damages but also triggering vas deferens motility defects. The correction of varicocele free from surgical technique may reverse the damaging of the vas deferens. Therefore when indicated surgical correction of varicocele is essential. It seems that varicocele surgery does not only prevent late term testicular and/or epididymal damages but also avoids vas deferens motility defects.
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PMID:The effects of varicocele and its surgical correction on vas deferens motility. 1804 Jun 96

Spermatozoa produced in the testis undergo maturation in the epididymis which secretes an osmolyte-rich fluid that bathes the sperm cells. These cells need to maintain their volume after ejaculation when they first encounter hypo-osmolal environments of accessory gland fluids and later within the female tract. If they do not, they experience swelling that is manifested in flagellar angulation that prevents their passage through cervical mucus or the uterotubal junction and they never reach the oocytes. This is a cause of male infertility in domestic species and certain infertile transgenic mice in which flagellar angulation has been shown to indicate cell swelling as a consequence of reduced epididymal provision of osmolytes. The reduced volume regulating ability of spermatozoa from subfertile boars and bulls has prompted study of volume regulation of spermatozoa as a possible cause of human male infertility. Understanding this process may make its manipulation possible and could suggest better sperm handling and storage techniques and thus provide therapy for infertile patients. On the other hand, volume regulation is a potential target for contraception if mimicking the conditions expressed by the "sterile studs" were possible. The evidence for the presence of ion channels probably responsible for regulatory volume decreases in spermatozoa is reviewed here that implicate voltage-gated potassium channels (especially Kv1.5 (KCNA5), minK (KCNE1) and TASK2 (KCNK5)) and the chloride channels CLCN3 and CLNS1A. The involvement of ion co-transporters in volume regulation of spermatozoa is also discussed.
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PMID:Involvement of potassium and chloride channels and other transporters in volume regulation by spermatozoa. 1804 71

The epididymis consists of a single, highly coiled and convoluted tubule that Antoine De Graaf, the famous 17th-century anatomist, likened to a thread thickening to a string. The uncoiled tubule is several meters long and sperm in transit through it become functionally mature under the under the influence of the tubule lumen's microenvironment. The regulation of that microenvironment and the manner by which it influences sperm maturation have been the topic of investigation for many years, though the study of the human epididymis directly is fraught with problems related to sample availability and condition. Nevertheless, investigations using a variety of mammalian tissue sources, human included, have resulted in significant advances in our understanding of both the biology and pathology of the organ. The epididymal functions of transporting, concentrating, maturing, and storing sperm are important to male fertility and their absence or significant impairment can be a factor in male infertility.
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PMID:De Graaf's thread: the human epididymis. 1822 12


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