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Objectives To determine whether cryptorchidism is a congenital malformation and whether the impaired spermatogenesis in immature testes can be reversed by early orchidopexy, using the mutant trans-scrotal (T-S) rat which is normally masculinized but has cryptorchidism in 85% of males. Materials and methods First, T-S rats (six per group) with ectopic testes destined to be undescended were investigated histologically at 4, 7 and 14 days after birth. Secondly, 12-day-old T-S rats were divided into four groups which underwent different procedures, i.e. 1, with normally descending testes (normal control, 10 rats); 2, with undescended testes (UDT) treated by orchidopexy (treated UDT, eight rats); 3, with UDT treated by a sham operation (sham-operated UDT, six rats); and 4, with UDT left untreated (untreated UDT, six rats). Thirty days after operation the testicular anatomy was recorded; excised testes were examined histologically and different types of germ cells were counted per tubule cross-section microscopically. Results There were no quantitative or morphological differences in the numbers of gonocytes, type-A spermatogonia or Leydig cells in the seminiferous tubules between normal and ectopic testes in the first 14 days after birth. However, by 21 days of age spermatogenesis in the UDT had declined with transformation from primary leptotene spermatocytes to spermatids. There were significantly more Leydig cells in the untreated UDT at 30 days than in normal control testes. The impaired spermatogenesis in UDT was restored by early orchidopexy and there were significantly more seminiferous tubules at stage 3 (pachytene spermatocytes) and stage 4 (spermatids) than in the untreated or sham-operated groups (P

Mutation screening of the BOULE gene in 156 men with azoospermia or severe oligozoospermia revealed no relevant mutations; thus, mutations in BOULE can be eliminated as a major cause of impaired spemiatogenesis. (C)2005 by American Society for Reproductive Medicine

In recent years, there have been major advances in microarray technology in terms of the number of genes under investigation (features) and the optimization of platforms. Starting with only 48 spotted cDNAs in 1995 [1], the past two decades have seen the development of many microarray platforms that can monitor the expression of thousands of genes simultaneously. Combined with the now standard method of cRNA amplification from small amounts of mRNA [2], as routinely encountered in biopsies, this offers the possibility of investigating global expression changes in small samples obtained from tumors or other clinical investigations.

Reproductive function is impaired in patients with severe renal insufficiency. In women, this is characterized by anovulation and decreased fertility; in men, by reduced testosterone production and impaired spermatogenesis. This chapter looks at the mechanisms behind these defects, and the therapeutic alterations that may ameliorate some of the problems, focusing on our own research in this area.

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants used to retard the ignition and/or spread of fire. PBDEs are used in various consumer products, such as textiles, mattresses and TV screens. This study presents a chemical risk assessment for the Irish population based on exposure to PBDEs from food. Special regard is given to the influence of parameter uncertainty and variability on the margins of safety. To quantitatively model uncertainty and variability in concentration data and variability in consumer behavior, a hierarchical probabilistic model was constructed. This model was evaluated using a two-dimensional Monte Carlo simulation (2D-MCS) approach. By considering uncertainty and variability in concentration data, margins of safety (MOS) were derived that are lower by a factor of ∼2 compared to MOS based on dose estimates that only consider variability. The lowest MOS is 7.5 × 104 for BDE-99, with impaired spermatogenesis as toxic endpoint. Assuming an MOS of 104 as acceptable, we conclude that there is no significant risk for human health through intake of contaminated food. To investigate whether additional measurements could improve the quality of dose estimates, the statistic “uncertainty-to-variability (UVR)” was developed. By applying the UVR to our dose estimates, we show that, in our case, the datasets contain little uncertainty and additional measurements would not significantly improve the quality of dose estimates.

Klinefelter syndrome (KS) is a genetic disorder in males characterized by the presence of an extra X chromosome. Its most consistent endocrinological manifestations include lower testosterone production and impaired spermatogenesis. KS individuals have a general typical appearance with taller stature, and they demonstrate a characteristic cognitive phenotype involving weaknesses in verbal processing. Anomalous cerebral lateralization involves the inverse or weak dominance of hand, language, and visuospatial abilities and has been associated with the cognitive deficits of KS individuals. This article summarizes the ongoing research in this field, discusses the main findings, and attempts to provide a thorough description of the cause of the observed functional and anatomical cerebral asymmetries associated with the syndrome. Nonetheless, efforts have been directed to incorporate evidence for and against theoretical accounts that explain the experimental findings, to discuss issues involving the implications of the chosen methodology, and present key research areas for future empirical research.

Notice of withdrawal: The following article from Molecular Reproduction and Development, "Impaired spermatogenesis in mice overexpressing stem cell protein Piwil2 (Mili)" by Lee JH, De Rooij DG, Schweyer S, Meinhardt A, M�ller C, Engel W, Nayernia K, published online on 23 Jun 2009 in Wiley InterScience (www.interscience.wiley.com), has been withdrawn from publication by agreement between the authors, the journal Editor in Chief Gary M. Wessel, and Wiley-Liss, Inc.

Performance testing started after it was recognized that growth traits were heritable. In the early years of performance testing there was a tendency to feed higher levels of energy for longer periods of time. More recently, the trend has been to feed lower levels of energy for shorter periods. There are still differences in opinion as to the appropriate level of energy to use. Although it is important that the level of energy fed is adequate to correctly establish a bull's ability to gain, it is essential to know that it will pose no risk of impaired spermatogenesis or cause any degree of laminitis. Clinical observations and research on overfeeding clearly show that both libido and spermatogenesis can be impaired by excess energy intake. The damage in 2-year-old bulls can be very extensive and in some animals it may not be reversible. The scant amount of research in yearling bulls indicates that there is considerable potential danger from overfeeding energy as well. Test stations are under used in regard to performing research that would help identify heritable defects that would interfere with the productive and reproductive efficiency of beef cattle. The first performance testing programs emphasized average daily gain from weaning to 1 year of age, so "performance" has traditionally meant rate of gain to most cattle raisers. The term "performance" is now starting to acquire a broader and more inclusive definition. For many breeders, it now includes weight per day of age, which is in part a maternal trait, and some kind of male evaluation for reproductive potential that can also be extrapolated to the female side. One of the first breakthroughs in this regard was to recognize the heritability of testicular size, and that testicular size could be fairly accurately determined by scrotal circumference measurement. It was also found that there was a favorable relationship between larger testicle size and the ability to produce high quality semen. As a result, it became a common practice to include scrotal circumference measurements in the published bull test results. However, many test station patrons were, and still are, content to consider the scrotal circumference measurement alone as an evaluation of a bull's breeding potential. Unfortunately, less than half of the bulls finishing a performance test at ages ranging from 11 to 14 months will be able to produce semen of completely acceptable quality.(ABSTRACT TRUNCATED AT 400 WORDS)

terone), and the period from SCI injury were also obtained and analyzed to detect any associations with the presence of spermatogenesis. RESULTS: In this series, SRR and PR were 89% and 62%, respectively. Univariate analysis identified age, testicular volume, serum LH level and serum FSH level as significant predictors of TESE outcome, of which only serum FSH level appeared to be independently related to TESE outcome on multivariate analysis (Table).

The ubiquitin-specific protease 26 (USP26) gene is an X-linked gene specifically expressed in testis tissue. This gene is therefore a potential infertility gene. In order to analyse its possible involvement in spermatogenesis and infertility, 42 patients with Sertoli cell-only syndrome were analysed for mutations in this gene. We found four patients with exactly the same three changes of the nucleotide and therefore also amino acid sequence. These patients showed 370-371insACA, 494T>C and 1423C>T causing T123-124ins, L165S and H475Y, respectively. These changes were not found in 10 control samples. Furthermore, two polymorphisms were observed which do not alter the amino-acid sequence. A restriction analysis that can make a distinction between a T and a C, at position 494, was set up in order to examine more patient and control samples. Another 69 patients with Sertoli cell-only syndrome, 32 patients with maturation arrest and 142 control samples were analysed using this method. None of the control samples or patients with maturation arrest featured the change at position 494. However, four more patients with Sertoli cell-only syndrome were identified with the three alterations. The frequency of alterations in this group is therefore 7.2% (8/111). One of the patients had a deletion of the long arm of the Y chromosome, while another patient had a varicocoele. These results indicate that these alterations might be involved in male infertility or might increase the risk of male infertility.

Y chromosome microdeletion screening is advised in cases of severely impaired spermatogenesis. Improvements in molecular biological techniques have made diagnosis more accessible in routine analysis. However, Y chromosome microdeletions are not diagnosed in all IVF centres. The aim of the present study was to determine the regulatory (indications, financing) and performance (methods, invoicing) conditions required for this analysis, in France. Microdeletion detection was found to be spreading fast and consistantly. It therefore seems necessary for a consensus to be reached on indications, with a view to a standardized technique, with a common effort of experts in the field. Financial management by the French Health Insurance bodies (Sécurité Sociale) would be an essential step towards routine adoption. Lastly, the answers to our questionnaire revealed a strong demand for information concerning this analysis.

no abstract available

Microdeletion of the Azoospermia Factor (AZF) regions in Y chromosome is a well-known genetic cause of male infertility resulting from spermatogenetic impairment. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. In this study, we characterized partial deletion of AZFc region in Korean patients with spermatogenetic impairment and assessed whether the DAZ and CDY1 contributes to the phenotype in patients with gr/gr deletions. Total of 377 patients with azoo-/oligozoospermia and 217controls were analyzed using multiplex polymerase chain reaction (PCR), analysis of DAZ-CDY1 sequence family variants (SFVs), and quantitative fluorescent (QF)-PCR. Of the 377 men with impaired spermatogenesis, 59 cases (15.6%) had partial AZFc deletions, including 32 gr/gr (8.5%), 22 b2/b3 (5.8%), four b1/b3 (1.1%) and one b3/b4 (0.3%) deletion. In comparison, 14 of 217 normozoospermic controls (6.5%) had partial AZFc deletions, including five gr/gr (2.3%) and nine b2/b3 (4.1%) deletions. The frequency of gr/gr deletions was significantly higher in the azoo-/oligozoospermic group than in the normozoospermic control group (p = 0.003; OR = 3.933; 95% CI = 1.509–10.250). Concerning Y haplogroup, we observed no significant differences in the frequency of gr/gr deletions between the case and the control groups in the YAP+ lineages, while gr/gr deletion were significantly higher in azoo-/oligozoospermia than normozoospermia in the YAP2 lineage (p = 0.004; OR = 6.341; 95% CI = 1.472–27.312). Our data suggested that gr/gr deletion is associated with impaired spermatogenesis in Koreans with YAP2 lineage, regardless of the gr/gr subtypes. Citation: Choi J, Song S-H, Bak CW, Sung SR, Yoon TK, et al. (2012) Impaired Spermatogenesis and gr/gr Deletions Related to Y Chromosome Haplogroups in Korean Men. PLoS ONE 7(8): e43550. doi:10.1371/journal.pone.0043550 Editor: Yong-Gang Yao, Kunming Institute of Zoology, Chinese Academy of Sciences, China Received February 7, 2012; Accepted July 23, 2012; Published August 23, 2012 Copyright: 2012 Choi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by a grant (A084923) of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish,or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: shshim@cha.ac.kr

Aims: This study was conducted to evaluate the outcomes of assisted reproductive technology (ART) procedures, viz., intrauterine insemination (IUI), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in males with impaired spermatogenesis. Settings and Design: The subjects of the study were infertile couples who were undergoing ART treatment due to male factor indications. The project was designed to correlate the outcome of the ART treatment and its efficacy in different study groups. Methods: Males were grouped as: 1. oligozoospermia (n = 153), 2. asthenoteratozoospermia (n = 158), 3. obstructive azoospermia (n = 110) and 4. nonobstructive azoospermia (n = 58). Patients from groups 1 and 2 were considered for IUI, IVF and ICSI. Those from group 3 were considered for IVF and ICSI and the 4th group underwent only ICSI treatment. Results: Oligozoospermia showed lower pregnancy rates with IUI than with both IVF and ICSI. An average minimum native and postharvest count was obtained to get an acceptable IUI outcome. Asthenoteratozoospermia had the lowest pregnancy rate with IUI as compared to IVF, whereas ICSI showed significantly higher pregnancy rates in this group. Obstructive azoospermia showed significant improvement with ICSI over IVF. In nonobstructive azoospermia, ICSI resulted in a 27.58% pregnancy rate. Conclusion: The IUI outcome was impressive though less effective whereas there was no difference between the IVF and ICSI outcomes in oligozoospermia. In asthenoteratozoospermia, ICSI showed a significant advantage over IUI and IVF, with IUI resulting in poor outcome in this group. In obstructive azoospermia, ICSI had a distinct advantage over IVF whereas in nonobstructive azoospermia, ICSI, the only option, was found to be effective and helpful in achieving an acceptable pregnancy rate.

About 30–40% of male infertility is due to unknown reasons. Genetic contributions to the disruption of spermatogenesis are suggested and amongst the genetic factors studied, Y chromosome microdeletions represent the most common one. Screening for microdeletions in AZFa, b and c region of Y chromosome showed a big variation among different studies. The purpose of this study was to investigate the prevalence of such deletions in Saudi men. A total of 257 patients with idiopathic oligo- or azoospermia were screened for Y chromosome microdeletions by 19 markers in AZF region. Ten (3.9%) patients had chromosomal rearrangements, six of them showed sex chromosome abnormalities and four patients had apparently balanced autosomal rearrengements. Eight of the remaining 247 patients (3.2%) with a normal karyotype and no known causes of impaired spermatogenesis had Y chromosome microdeletions. Among these, six patients had deletions in AZFc region, one case had a deletion in AZFb and another had both AZFa and AZFc deletions. In conclusion, our study shows that Y chromosome microdeletions are low in our population. We also report for the first time a case with unique point deletions of AZFa and AZFc regions. The lower frequency of deletions in our study suggest that other genetic, epigenetic, nutritional and local factors may be responsible for idiopathic oligo- or azoospermia in the Saudi population.

The negative influence of some insecticides on male fertility has been noted. We report our cytogenetic observations on a group of infertile insecticide workers. Increased chromosomal breakage was a constant finding and the Y chromosome was especially damaged. This may account for impaired spermatogenesis. Furthermore, the involvement of heterochromatic chromosomal variants both in the individual susceptibility to the chemically induced damage and in the reproductive fitness is emphasized.

Using a new experimental model of cryptorchism in rats, where testicular descent was prevented, testicular development and function were studied in bilateral and unilateral cryptorchid animals Morphometric and radioimmunological techniques were used. Up to 30 days after birth testicular development was identical in the two types of abdominal testes but in adult rats differences were observed. In these rats spermatogenesis was damaged to a similar extent, but total tubular length and testicular weight were increased in the bilateral abdominal testes. Moreover, in these testes, the volume density of Leydig cells, the total Leydig cell mass, the average Leydig cell size and the testis testosterone concentration were larger than in unilateral abdominal testes. It is suggested that the impaired spermatogenesis seen in both kinds of abdominal testes may be unrelated to Leydig cell function.

A patient with male pseudohermaphroditism is presented whose testicular biopsy showed marked paucity of the Leydig cell populations to which is attributed testosterone deficiency and impaired spermatogenesis.

SEVERAL workers have observed that reserpine has very little effect on the reproductive performance of chickens (Anderson and Smyth, 1959; Weiss, 1959; Carlson, 1959; Gilbreath et al., 1960). However, evidence was presented by Van Matre et al. (1957) and Parker (1960) which indicates that reserpine may alleviate decreases in egg production during stress conditions. In other avian classes it has been shown that this tranquilizer causes certain reproductive inhibitions. Reserpine administered to male pigeons by Khazan et al. (1960) caused a severe atrophy of the testes. Histological sections of the testes showed impaired spermatogenesis. Hewitt and Reynolds (1957) found that reserpine reduced egg production, fertility and hatchability in pheasant breeders. In growing turkeys aortic rupture has been successfully controlled with the use of reserpine (Couch, 1959; Carlson, 1959; Morrison, 1960; Barnett, 1960); however, the effects of the drug on the reproductive performance of this species have not been described. The …

Summary In an unselected series of 120 autopsies performed upon male New Guineans there were 20 children of whom 10 had evidence of healed arteritis of testicular vessels. Forty-eight of the 100 adults had absent spermatogenesis due to testicular atrophy and fibrosis which was associated with vascular occlusion possibly due to old angiitis. Fifty-two of the 100 adults had active spermatogenesis but in 6 there was complete atrophy of one testis and in 24 there were atrophic tubules scattered amongst the normal ones.

The influence of a sub-tropical climate and high temperature on the reproduction of cattle in Southern Africa is discussed. High temperatures result in impaired spermatogenesis in indigenous and exotic bulls but the former are more resistent to these effects. In the female the effects of climate on growth and development of heifers is examined. High temperature during pregnancy result in the birth of immature offspring in unadapted breeds. Factors effecting reproduction in ranch cows are examined.

AMONG functioning adrenocortical tumors, those with activity confined largely to the secretion of pathogenic quantities of estrogens are by far the most unusual. In 1948 Wilkins (1) reviewed the data on 10 patients with “feminizing” tumors which had led to gynecomastia and a variable regression of masculine characteristics, and contributed the details in 2 more patients, one an adult studied by W. W. Scott and the other a 5-yearold boy. Four additional cases (2, 3, 4) have been reported since then. In most of these instances the tumors have been malignant and in all of them the development of the gynecomastia and other signs has been rather acute and intense. The patient to be described in this report differed from these in that he was shown to have a large benign tumor which was judged to have been present in a moderately active state for sixteen years, the oversecretion of estrogens leading to a relatively stable gynecomastia, mild hypogonadism and impaired spermatogenesis. The age at onset, the moderat...

Cryptorchidism is associated with impaired spermatogenesis and, at times, sterility. Early orchiopexy has been advocated as a possible means to prevent spermatogenic impairment and infertility in patients with cryptorchidism. This retrospective study is derived from data obtained from 74 cases that were observed during a period of approximately 10 years at our hospital. Particular attention was devoted to epididymal and vas deferens histological status. Of the 47 epididymides and vas deferens examined only 2 epididymides and 2 vas deferens showed histological maturity. The remainder showed varying degrees of immaturity that additionally correlated, when testicular tissue was available, with the presence of unfavorable testicular histological findings. Cryptorchidism is associated with changes in the gonads and spermatic duct system.

The surface temperature of the scrotum is influenced by that of the testes and the underlying blood vessels. Whereas in the normal healthy male the temperature distribution is symmetrical with a warmer region over the septum, reversal of blood flow in the internal spermatic vein can cause a varicocele which may result in an abnormal temperature increase in the scrotum. IR thermography can be used to detect, measure and record the extent of this thermal abnormality.1,2 The clinical condition affects about 10% of young men3 and it occurs in about 20% of subfertile males4 when it may be associated with a variable degree of impaired spermatogenesis.5 Clinically, it may be difficult to decide upon the presence or absence of a varicocele and it is even more difficult to be sure whether the abnormality is unilateral or bilateral. Although the mere existence of a varicocele is not by itself an indication for surgery if other findings are normal, thermography can provide accurate objective evidence of disturbed scrotal temperature, which may be important in a subfertile man with evidence of impaired spermatogenesis. The results of surgery are not uniformly good and improvement in semen quality may not occur until the temperature abnormality has been corrected, which may require re-operation.6

The effects of unilateral scrotal and abdominal vasectomy in rats with and without ligation of the ductus deferens were compared in an experimental situation which allowed early identification of cryptorchism. 6.4% of the rats devleoped cryptorchism following surgery: 5 on the control side 3 on the operated side and 1 on both sides. All 3 cases of left-sided cryptorchism occurred in the abdominal vasectomy group. Vasectomy with ligation was associated with a significant (p< .01) increase in the weight of the operated testes. The surgical procedure of vasectomy appears to have little influence on testicular weight or sperm concentration. There was no evidence of impaired spermatogenesis in rats vasectomized by various procedures.

Summary— Investigation of 311 azoospermic males has shown that the combination of estimation of testicular size and plasma FSH allows the spermatogenic funciton of th testes to be accurately assessed by non-invasive method. Patients with small testes and grossly elevated levels of plasma FSH have absent, or grossly impaired spermatogenesis, and do not require surgical exploraion. They should be advised with regard to adoption or artificial inseminaition. Patients with large testes (5 cm) or an FSH level which is not grossly elevated require operation and should undergo a surgical exploration and the possible corretion of an obstructive lesion. A testicular biopsy is essential if no obstructive lesion is found as the histology of these patients may show a spermatolgenic arrest.

Recent studies indicate that Mesterolone (1 Methyl-5 androstane-17-o1-3-one) is a valuable drug in the treatment of impaired spermatogenesis and some sexual disorders1,2,3. It now appears that Mesterolone may be more effective than many other frequently used oral testosterone preparations4,5. This steroid exhibits adequate androgenic and spermatogenetic effects with no apparent impairment of liver functions. In this communication we are reporting our results obtained on patients treated with Mesterolone, for various sexual and fertility disorders6. Previous studies on the efficacity of Mesterolone, were carried out mainly on experimental animals and on small number of patients 4,7,8. To the best of our knowledge, we are the first to report on the effects of Mesterolone on a large series of patients, who were carefully evaluated as to their response to this steroid, from different clinical, hormonal and biochemical parameters.

Fertility after late spontaneous descent of the testes in 45 men with previous bilateral undescended testes was evaluated on the basis of seminal analysis and concentrations of follicle-stimulating hormone (FSH) in serum. Only 15 (33 per cent) were found to have a normal fertility as estimated from the results of the total semen analysis, whereas 21 (47 per cent) were classified as being sterile or having severely reduced fertility. Elevated serum FSH concentrations in the majority of men with subnormal sperm densities supported the results of the semen analysis, indicating impaired spermatogenesis. These findings suggest that the expectant attitude in the treatment of cryptorchidism does not seem to be justified in terms of fertility and combined with recent histomorphological studies favour a more active and early treatment of undescended testes.

Scrotal temperatures, testicular volumes, and sperm characteristics were studied in 150 infertile, nonazoospermic men and in 37 fertile men, used as a control group. The mean scrotal temperature values of the infertile men were significantly greater than those observed in the fertile men (+0.4 degrees C for the right; +0.5 degrees C for the left). In the infertile men, it was found that the higher the scrotal temperature, the more alterated the sperm characteristics. The only clinical element that seemed to be linked to the existence of scrotal hyperthermia in the infertile men was testicular hypotrophy. Although the scrotal temperatures of the infertile men with varicocele were significantly higher than those of the fertile men, they did not significantly differ from those of the infertile men without varicocele. No other specific pathologic factor, infectious or surgical urogenital history was found to be responsible for the scrotal hyperthermia observed in the infertile men.

Background The LIM domain protein Fhl5 was previously found to interact with CREM, a DNA binding transcriptional regulator necessary for spermiogenesis in mammals. Co-transfection experiments using heterologous promoter constructs indicated a role for Fhl5 in transcriptional up-regulation of CREM-dependent testicular genes. Male mice lacking Fhl5 were reported to be fertile but displayed partially abnormal sperm maturation and morphology. Methods To identify Fhl5 testicular target genes we carried out two whole-genome expression profiling experiments using high-density oligonucleotide microarrays and total testis samples from Fhl5 wild-type versus homozygous mutant mice first in different and then in isogenic strain backgrounds. Results Weak signal differences were detected in non-isogenic samples but no statistically significant expression changes were observed when isogenic Fhl5 mutant and wild-type samples were compared. Conclusion The outcome of these experiments suggests that testicular expression profiling is extremely sensitive to the genetic background and that Fhl5 is not essential for testicular gene expression to a level detected by microarray-based measurements. This might be due to redundant function of the related and similarly expressed protein Fhl4.