层黏连蛋白受体在小鼠睾丸和附睾中的表达

目的 探讨层黏连蛋白受体(LAMR1)在小鼠睾丸和附睾中的表达.方法收集3只正常成年昆明小鼠睾丸和附睾.采用原位杂交和免疫组织化学方法,检测LAMR1 mRNA及蛋白在成年小鼠睾丸和附睾中的分布.结果 LAMR1 mRNA在附睾头和附睾尾表达最强;在睾丸生精细胞中也有表达.免疫组织化学结果显示,LAMR1蛋白从附睾头到...     

The relative viability of human spermatozoa from the vas deferens, epididymis and testis before and after cryopreservation

Testicular and epididymal spermatozoa are routinely used with in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) to achieve pregnancies. In addition, excess cryopreserved spermatozoa can be thawed and used for ICSI. However, information on the recovery of epididymal and testicular spermatozoa after freeze-thaw is lacking. This is important to determine the feasibility of using previously cryopreserved aspirated spermatozoa for ICSI. We prospectively compared the viability of fresh and frozen-thawed spermatozoa from the vas deferens, epididymis and testicle by several measures. Testis spermatozoa were obtained from men with non-obstructive azoospermia (n = 5), epididymal spermatozoa from men with obstructive azoospermia (n = 8), and vasal spermatozoa from fertile men by vasal irrigation at vasectomy (n = 5). The viability of fresh spermatozoa was assessed by motility, two vital stains (carboxyfluorescein, 0.08 mg/ml and propidium iodide, 20 mg/ml) and the hypo-osmotic swelling assay (HOS; 100 mmol/l citrate and fructose). After cryopreservation, spermatozoa were thawed and all viability measures repeated. Although fresh vasal spermatozoa were the most motile, testicular spermatozoa exhibited similar, high viability (91 and 86% respectively) by vital stain. Spermatozoa from testis, epididymis and vas deferens survived cryopreservation equally well by vital stain, but not by motility. As a selection measure, the HOS assay identified significantly more viable epididymal and testicular spermatozoa than did motility in both fresh and frozen-thawed populations. It appears feasible to use frozen-thawed extracted spermatozoa for ICSI when motility and a selection measure such as the HOS assay are used. With fresh testis spermatozoa, selection methods may not be necessary prior to ICSI, as cell viability is high.     

Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI

BACKGROUND: Although ICSI provides a way of treating azoospermic men, concern has been raised about the potential risk for transmission of genetic abnormalities to the offspring. We quantified the incidence of chromosomal abnormalities in epididymal and testicular sperm retrieved from azoospermic patients undergoing ICSI. METHODS: Individual testicular sperm were collected from testicular biopsies with an ICSI pipette, and epididymal sperm were retrieved by microsurgical epididymal sperm aspiration. Samples were processed by fluorescent in-situ hybridization (FISH) for chromosomes 18, 21, X and Y and the results compared with those from normal ejaculated samples. RESULTS: The overall aneuploidy rate of 11.4% in men with non-obstructive azoospermia was significantly higher (P = 0.0001) than the 1.8% detected in epididymal sperm from men with obstructive azoospermia and also the 1.5% found in ejaculated sperm. No significant difference was found between the epididymal and ejaculated samples. When the chromosomal abnormalities were analysed, gonosomal disomy was the most recurrent abnormality in both obstructive and non-obstructive azoospermic patients, while autosomal disomy was the most frequent in ejaculated sperm. CONCLUSIONS: Sperm of non-obstructive azoospermic men had a higher incidence of chromosomal abnormalities, of which sex chromosome aneuploidy was the most predominant. Genetic counselling should be offered to all couples considering infertility treatment by ICSI with testicular sperm.     

Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and testicular germ cells of infertile patients

The hypothesis that sperm aneuploidy and diploidy increase as a function of spermatogenesis impairment was addressed. Ejaculated semen samples from a series of men (n = 22) with very low total normal motile count (1 x 10(6)) was analysed in terms of sperm aneuploidy and diploidy by in-situ hybridization and compared with controls (n = 10). Germ cell aneuploidy was also analysed in an additional series of infertile patients presenting unexplained infertility (n = 3), congenital absence of the vas deferens (CAVD) (n = 6) and non-obstructive azoospermia (n = 3) undergoing IVF, microsurgical epididymal sperm aspiration (MESA)/ICSI and testicular sperm extraction (TESE)/ICSI cycles respectively. In-situ hybridization for chromosomes 1, 17, X and Y was performed on ejaculate, epididymal and testicular spermatozoa. Significantly higher sperm aneuploidy and diploidy rates where found (for the four chromosomes analysed) in spermatozoa from oligoasthenoteratozoospermia (OAT) over controls (18 versus 2.28% and 2.8 versus 0.13% respectively; P < 0.001). Testicular germ cells had even higher rates of sperm aneuploidy and diploidy. However, in this group it was difficult to determine whether the cells analysed were dysmorphic spermatozoa or spermatids. The data warrant further investigation on the cytogenetic abnormalities found in most germ cells identified in testicular tissue biopsies of azoospermic patients.     

Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm

BACKGROUND: Follow-up studies of children conceived after ICSI using epididymal or testicular sperm are important due to a still more extensive use of immature male germ cells for ICSI. It is, however, difficult to evaluate the potential risks of malformations of children born after ICSI, overcoming the natural fertilization processes, due to methodological limitations. METHODS: Follow-up study including all children born in Denmark and Norway following ICSI in Denmark, using epididymal or testicular sperm, was done. A questionnaire was sent to the parents between 3 months and 7 years after delivery. RESULTS: Of 341 couples, 329 returned the questionnaire giving a response rate of 96.5%. The study included 412 children, 225 girls and 187 boys, giving a sex ratio (males/males + females) of 45.4% compared with 53.1% in Danish children conceived after conventional IVF without ICSI (P < 0.005). Among a total of 14 (3.4%; 95% confidence interval (CI): 1.9%-5.7%) major malformations, three boys with hypospadias were the most remarkable finding (1.6%; 95% CI: 0.33-4.7%). CONCLUSIONS: An increased frequency of hypospadias in the male offsprings was seen compared with the general population. Apart from this, no increased major malformation rate was detected in ICSI children conceived with epididymal or testicular sperm when compared with malformation rates for IVF or spontaneously conceived children reported in the literature. The sex ratio was significantly lower for ICSI children conceived with epididymal or testicular sperm when compared with children conceived with conventional IVF.     

Influence of macrophage migration inhibitory factor (MIF) on the zinc content and redox state of protein-bound sulphydryl groups in rat sperm: indications for a new role of MIF in sperm maturation

The function of macrophage migration inhibitory factor (MIF) in sperm maturation was studied by investigating its role in the biochemical maturation of the outer dense fibres. Rat sperm obtained from the caput and cauda epididymis were stimulated overnight with either recombinant MIF or MIF-containing vesicles originating from epididymal fluid at various concentrations. The zinc content of both the sperm and the medium was determined by means of atomic absorption spectrometry. Incubation in both recombinant MIF and vesicular MIF resulted in a statistically significant decrease of the zinc content in stimulated caput sperm of approximately 50%. In parallel, the conditioned media showed a clear increase in the concentration of this trace metal. The effect of MIF was less marked in cauda sperm. In addition, we demonstrated a statistically significant increase of detectable free thiol groups in the sperm mid- and principle piece in isolated rat sperm after stimulation with MIF at concentrations of 25 and 50 ng/ml. Our data suggest that MIF plays an important role in the maturation process of rat sperm during epididymal transit by inducing the elimination of zinc and affecting the amount of free sulphydryl groups in the sperm flagella.     

Reduced oocyte activation and first cleavage rate after ICSI with spermatozoa from a sterile mouse chromosome mutant

BACKGROUND: Male mice, heterozygous for two semi-identical reciprocal translocations T(1;13)70H and T(1;13)1Wa are usually sterile. We have investigated this oligoasthenoteratozoospermic mouse model using ICSI. METHODS: B6D2F1 oocytes were injected with epididymal or testicular sperm from fertile or sterile translocation carriers and from chromosomally normal fertile controls. ICSI efficiency was determined by pronucleus formation and first cleavage rates. For arrested zygotes, cell cycle progression was evaluated by BrdU incorporation and incubation with okadaic acid. RESULTS: Epididymal sperm from infertile translocation carriers showed a slightly lower fertilization rate (70% vs. 92%, 95% and 95% for fertile translocation carriers and two groups of normal fertile control males, respectively) and a severely reduced cleavage rate (33% vs. 87%, 96% and 89% for the same control groups). However, the use of testicular sperm significantly improved the cleavage rate (62% vs. 83% for normal fertile controls). Development of arrested zygotes was delayed or blocked during S- and G2-phase. CONCLUSIONS: Whereas control testicular and epididymal sperm performed equally well, the use of testicular sperm from oligospermic T/T' males significantly increased first cleavage rates when compared to the low rates with epididymal sperm. Epididymal storage in oligospermics may negatively influence zygote division.     

Effects of Estrogen Treatment on Aging in the Rat Epididymis

Previous studies from our laboratory demonstrated that estrogen signaling in the testis contributes to maintaining spermatogenesis in adult rats, and that estrogen treatment attenuated the age-associated decline in sperm production. The purpose of this study was to determine if epididymal function is also altered with age, and what effects estrogen treatment may have on the epididymis during aging. We compared untreated rats at 3 and 15 months of age to 18-month-old vehicle-treated and estrogen treated rats. In all four groups, tubule and lumen diameter of the cauda was significantly larger than more proximal regions of the epididymis. In the 3-, 15-, and 18-month-old treated animals, the epithelial cell height of the cauda was significantly shorter than that of more proximal regions. The caput cell height was shorter at 18 months compared to 3 months but this was not seen in estrogen treated animals. Thus, estrogen appears able to prevent some age related changes in epididymal morphology. Sperm transit time through the distal cauda was significantly delayed with aging. Estrogen treatment prevented this delay, indicating that sperm transit through the epididymis is an estrogen regulated function. Differences in estradiol and testosterone concentrations were observed between 3- and 15-month-old animals, but no further differences were noted between treated or untreated animals at 18 months. Interestingly, expression of androgen receptor and estrogen receptor alpha were similar between ages and treatments. Collectively, these results suggest epididymal morphology and function are affected by aging and estrogen treatment. Anat Rec, 302:1447–1457, 2019. © 2018 Wiley Periodicals, Inc.     

Recent biochemical approaches to post-testicular, epididymal contraception.

Results from recent animal models with implications for putative human male contraceptives acting on the epididymis are reviewed. Inducing sterility by enhancing sperm transport through the epididymis has not been achieved. The induction of infertility in males of several species is easier to achieve by direct actions of drugs on sperm function (e.g. inhibition of sperm-specific isoenzymes of the glycolytic pathway by chloro-compounds) than by indirectly reducing amounts of epididymal secretions normally present in high concentration (e.g. alpha-glucosidase, L-carnitine). The former show promise for the clinic since human spermatozoa are susceptible to inhibition. On the other hand, the infertile male mice of the c-ros knock-out model demonstrate the influence of even a small region of the epididymis on fertility, so that targeting the as yet unknown epididymal factors presumably secreted in limiting amounts by this epididymal segment, is a new lead for a contraceptive. Targeting a specific sperm protein acquired in the testis, but depleted in the epididymis by toxicants that induce rapid infertility, may also lead to the discovery of new contraceptives, but these will require developing new means of organ-specific delivery of contraceptive drugs.     

High fertilization and pregnancy rate after intracytoplasmic sperm injection with spermatozoa obtained from testicle biopsy

In cases requiring microsurgical epididymal sperm aspiration(MESA) for congenital absence of the vas deferens (CAVD) orirreparable obstructive azoospermia, often no spermatozoa canbe retrieved from the epididymis, or there may even be no epididymispresent. We wished to see whether testicular biopsy with testicularsperm extraction (TESE) in such cases could yield spermatozoathat would result in successful fertilization and pregnancy(despite the absence of epididymal spermatozoa) using intracytoplasmicsperm injection (ICSI). In the same setting during the same2-week period, 28 patients with CAVD or irreparable obstructionwere treated; 16 consecutive fresh MESA—ICSI cycles and12 cycles which required testicular biopsy with testicular spermextraction (TESE—ICSI) were performed. Normal two-pronuclearfertilization rates were similar in both groups: 45% for epididymalspermatozoa and 46% for testicular biopsy-extracted spermatozoa.Cleavage rates were also similar (68% for epididymal and 65%for testicular spermatozoa). The ongoing pregnancy rates inthis series were 50 and 43% respectively. We conclude that epididymalspermatozoa and testicular spermatozoa yield similar fertilization,cleavage and ongoing pregnancy rates using ICSI. When epididymalspermatozoa cannot be retrieved, a testicular biopsy can beperformed and the few barely motile spermatozoa thus obtainedcan be used for ICSI. It appears that all cases of obstructiveazoospermia can now be successfully treated.     

ICSI outcomes in obstructive azoospermia: influence of the origin of surgically retrieved spermatozoa and the cause of obstruction

BACKGROUND: Spermatozoa can be retrieved from the testis and epididymis of men with obstructive azoospermia (OA) and used for ICSI. However, it is unknown whether the outcome of ICSI depends on the cause of obstruction or the origin of surgically retrieved spermatozoa. METHODS: A cohort of 171 men with OA and normal spermatogenesis were included in this retrospective study. They were divided into three groups according to the site and origin of obstruction: 83 men had congenital bilateral absence of vas deferens; 55 and 33 had acquired epididymal and deferent duct obstructions, respectively. The outcome of 368 ICSI cycles was determined and compared according to the origin of spermatozoa: epididymal (n = 253) or testicular (n = 115). RESULTS: Fertilization and clinical pregnancy rates did not differ between spermatozoa of different origin (58.9% versus 51.9% and 22.1% versus 24.3% with epididymal and testicular spermatozoa, respectively). However, the miscarriage rate was significantly higher for testicular spermatozoa (35.7% versus. 12.5% P < 0.05, chi2 test). Findings were similar whatever the aetiology of the OA. CONCLUSION: This study suggests that the use of testicular spermatozoa, even those generated during normal spermatogenesis, alters embryonic development and that epididymal spermatozoa should be preferentially used, irrespective of the aetiology of OA.     

Andrology: Changes in chromatin condensation of human spermatozoa during epididymal transit as determined by flow cytometry

Inasmuch as caput epididymal and even testicular spermatozoaare now being used to generate pregnancies by direct injectioninto the oocyte, differences in the chromatin of spermatozoafrom proximal and distal locations in the epidldymis were studied.Acridine Orange staining was used to investigate chromatin structurein human spermatozoa which had left the testis and were undergoingmaturation in the epididymis. Measurement of green and red fluorescenceIntensities of human spermatozoa by flow cytometry demonstrateda decrease in binding of Acridine Orange to DNA as the spermatozoatraversed the epididymis. Using spermatozoa from the cauda epididymisas the standard, the percentages of spermatozoa from the efferentduct, proximal corpus epididymis, midcorpus epididymis, distalcorpus epididymis, proximal cauda epidldymis and distal caudaepididymis that had matured with regard to chromatin condensationwere 28 ± 5, 39 ± 3, 49 ± 5, 64 ±5, 69 ± 6 and 74 ± 4% respectively. It may beconcluded that eggs fertilized by ejaculated spermatozoa receivea more highly condensed form of chromatin than that receivedby eggs Inseminated with proximal epididymal or testicular spermatozoa.     

Posthumous sperm retrieval: analysis of time interval to harvest sperm

BACKGROUND: Current recommendations regarding posthumous sperm retrieval (PSR) are based on a small number of cases. Our purpose was to determine the time interval from death to a successful procedure. METHODS: Seventeen consecutive PSR procedures in 14 deceased and 3 neurologically brain-dead patients at two male infertility centres [Sheba Medical Center (SMC), Tel-Hashomer, Israel and University of California San Francisco (UCSF), San Francisco, CA, USA] were analysed. Main outcome measures were retrieval of vital sperm, pregnancies and births. RESULTS: PSR methods included resection of testis and epididymis (n = 8), en-block excision of testis, epididymis and proximal vas deferens with vasal irrigation (n = 6), electroejaculation (EEJ) (n = 2) and epididymectomy (n = 1). PSR was performed 7.5-36 h after death. Sperm was retrieved in all cases and was motile in 14 cases. In two cases, testicular and epididymal tissues were cryopreserved without sperm evaluation, and in one case, no motility was detected. IVF and ICSI were performed in two cases in which sperm had been retrieved 30 h after death, and both resulted in pregnancies and live births. CONCLUSIONS: Viable sperm is obtainable with PSR well after the currently recommended 24-h time interval. PSR should be considered up to 36 h after death, following appropriate evaluation. No correlation was found between cause of death and chance for successful sperm retrieval.     

Androgen regulation of glycosidase secretion in epithelial cell cultures from human epididymis.

The human epididymis and its secretions actively promote sperm fertilizing capacity and provide protection for spermatozoa against harmful influences. Among epididymal secretions, glycosidases have been recently studied and associated with molecular changes on the sperm surface. In the present work, we studied the influence of different concentrations of testosterone, dihydrotestosterone and cyproterone acetate on the secretion of alpha-glucosidase, N-acetyl-glucosaminidase, beta-glucuronidase and alpha-mannosidase by isolated and cultured epithelial cells from human caput, corpus and cauda epididymides. Cell cultures were obtained from aggregates of isolated tubule fragments plated on extracellular matrix-covered multi-well plates. Activities of the glycosidases were measured in conditioned culture media and were higher in the distal regions of the epididymis. Testosterone and dihydrotestosterone significantly increase the enzyme secretion in a concentration-dependent manner. This increase was higher in corpus and/or cauda than in caput epididymis. Cyproterone acetate caused a dose-dependent decrease in glycosidase secretion in cultures from all epididymal regions. It is concluded that the secretion of epididymal glycosidases is regulated by androgen, being stimulated by dihydrotestosterone and testosterone and inhibited by the androgen antagonist cyproterone acetate.     

Induction of spermatogenesis in azoospermic men after internal spermatic vein embolization for the treatment of varicocele

BACKGROUND: To evaluate the improvement in semen quality and pregnancy rate after internal spermatic vein (ISV) embolization in men with nonobstructive azoospermia virtual azoospermia, or extremely severe oligoteratoasthenoazoospermia (OTA). METHODS: A prospective cohort of 101 azoospermic or severe oligoteratoasthenospermic men of mean (+/-SD) age 34.1+/-7.7 years who underwent ISV between September 1998 and June 2003 were evaluated for semen characteristics, endocrinology profile, and conception rate. RESULTS: Significant improvement was noted in mean sperm concentration, motility, and morphology in 83 men (82%). Mean sperm concentration increased from 0.22+/-0.30 x 10(6)/ml total sperm in the ejaculate to 9.28+/-1.2 x 10(6)/ml after embolization (P < 0.001); mean sperm motility rose from 8.78+/-1.59 to 29.56+/-2.0% (P < 0.001), and mean sperm morphology rose from 3.79+/-0.74 to 13.72+/-1.37% (P < 0.005). Pregnancy was achieved in 34 cases (34%), 20 (20%) unassisted and 14 (14%) assisted. CONCLUSIONS: Based on our findings, the following statements can be made: (i) Varicocele may cause any variation of severity in OTA, including azoospermia. (ii) Since male fertility is preserved with only one testis, OTA, azoospermia or virtual azoospermia represent bilateral testicular dysfunction. (iii) Treatment of bilateral varicocele may reverse testicular dysfunction and improve spermatognesis and testosterone production in men with extremely severe OTA and induce sperm production in men with azoospermia and virtual azoospermia. (iv) If azoospermia is not too long-standing, the treatment of varicocele may significantly improve spermatogenesis and renew sperm production. (v) Adequate treatment may spare in > 50% of azoospermic patients the need for testicular sperm extraction as preparation for ICSI. (vi) Since achievement of pregnancy in IVF units is higher when spermatogenesis is better, the treatment of varicocele (bilateral) is an effective medical adjunct for the IVF units prior to the treatment. We recommend that infertile men with azoospermia or virtual azoospermia or extremely severe OTA be evaluated for varicocele, with special attention to its bilateral nature.     

Maturation of spermatozoa in the epididymis of the Chinese hamster

Chinese hamster spermatozoa gain their ability to move when they descend from the testis to the distal part of the caput epididymis, but it is not until they enter the corpus epididymis that they become capable of fertilizing eggs. The maturation of the spermatozoa proceeds as they further descend the tract and perhaps continues even in the vas deferens. During transit between the distal caput and proximal cauda epididymides, small membrane-limited vesicles (and tubules) appear on the plasma membrane over the acro somes of the spermatozoa. The number of vesicles appearing on the sperm brane reaches a maximum when the spermatozoa are in the proximal cauda epididymis. It declines sharply in the distal cauda epididymis. Spermatozoa in the vas deferens are free of the vesicles. The origin, chemical nature, and functional role of the vesicles that appear on the sperm surface during epididymal transit must be the subject of further investigation.     

Mutagenesis-generated mouse models of human infertility with abnormal sperm

BACKGROUND: The aetiology of human male fertility, with impairment of sperm number, motility and morphology (oligoasthenoteratozoospermia), has been difficult to understand, partly for lack of animal models. METHODS: An ethylnitrosourea (ENU) mutagenesis strategy has been successful in producing heritable gene mutations with phenotypes similar to human male infertility, and here, we describe three independent ENU-induced mutations that cause a phenotype of oligoasthenoteratozoospermia in mice. RESULTS: The loci identified by these three mutations are designated swm2, repro2 and repro3. All mutant males were characterized by low sperm concentration, poor sperm morphology and negligible motility, but the infertile males were apparently normal in other respects. Sperm from mutant males failed to fertilize oocytes in vitro. Ultrastructural analyses revealed varied abnormalities apparent in both testicular spermatids and epididymal sperm. Genetic mapping placed the swm2 gene on chromosome 7, the repro2 gene on chromosome 5 and the repro3 gene on chromosome 10. CONCLUSION: The single-gene mutations caused complex and non-specific sperm pathologies, a point with important implications for managing cases of human male infertility. The ultimate identification of the loci for the mutations causing these phenotypes will clarify aetiology of complex syndromes of infertility with sperm abnormalities consistent with oligoasthenoteratozoospermia.     

Mouse Sperm Rosette: Assembling During Epididymal Transit,in vitro Disassemble,and Oligosaccharide Participation in the Linkage Material

In many mammals, sperm associations had been observed, but not in the mouse. In this work, mouse sperm rosettes are morphologically described inside the epididymis and during its dissolution in a culture medium. Also characterized are the saccharides present in the linking material. Sperm association and other epididymal actions are supported by sperm during epididymal transit and are verified at the caudal region, suggesting a relation between epididymal transit and sperm maturation. In drops of epididymal content obtained from distal (cauda), but not from proximal (caput and corpus) regions; dissolved in culture medium, rosettes appear to be 10 to 15 motile sperm joined by their heads. After 3 min, sperm progressively detach, disassembling the rosette. These structures are studied by several techniques, including optic, electronic (scanning electron microscopy and transmission electron microscopy), and video microscopy. At the ultrastructural level, a dense network of electron‐dense material was observed between sperm heads, joining them. Based on previous works in rat, several lectins were used to characterize the type of saccharides present in this linking material. To avoid the contact between sperm and epididymal fluid from distal region—that probably exerts an influence on sperm association—a ligature was placed between caput and corpus. This epididymal content isolated from caput did not display any rosettes after 28 days. Anat Rec, 2007. © 2007 Wiley‐Liss, Inc.     

The rate of aneuploidy is altered in spermatids from infertile mice

BACKGROUND: It is now possible for infertile males to father their own genetic children through the technique of ICSI. This prospect has consequently prompted several investigations into the quality of sperm being retrieved from infertile males. One potential risk is the use of aneuploid sperm or spermatids, which might then be transferred to the fertilized oocyte. METHODS: In this investigation, aneuploidy of spermatids was assessed through immunocytochemistry using antibodies directed against chromosome centromeric regions and complexes. Three different types of infertile male mice with phenotypes closely resembling those described in human non-obstructive azoospermia [PP1cgamma-deficient mice, CREM-deficient mice and C57BL/6J.MAC-17(0--23) mice] were examined for chromosome numbers by counting the number of kinetochores in round spermatids using a CREST antiserum. RESULTS: PP1cgamma(-/-) and CREM(-/-) spermatids from infertile mice showed highly significant elevated levels in the rate of aneuploidy compared with wild-type animals (P < 0.0001). Thus infertile males with independent genetic mutations resulting in different histopathologies showed a high risk in the level of aneuploidy in their spermatids. CONCLUSIONS: These results suggest that impaired spermatogenesis may lead to production of aneuploid gametes. Analysis of aneuploidy in gametes from infertile men, coupled with appropriate genetic counselling, is recommended prior to ICSI.