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Deoxyribonucleic acid methylation abnormalities at imprinted loci in oligospermic and azoospermic men.

OBJECTIVE: To assess deoxyribonucleic acid (DNA) methylation at imprinted and repetitive genomic regions in ejaculated and testicular sperm from men with oligospermia, azoospermia, and those undergoing vasectomy reversal (VR), compared with fertile controls. DESIGN: Observational case-control study. SUBJECTS: Samples were obtained from 68 men, including 29 infertile men (18 oligospermic [5-15 million/mL], 11 severely oligospermic [<5 million/mL]) and 20 fertile controls with confirmed natural conceptions. Testicular tissue was collected from 11 azoospermic men (7 obstructive azoospermia [OA], 4 nonobstructive azoospermia [NOA]) and 8 men with prior paternity undergoing VR. EXPOSURE: Sperm DNA methylation at four imprinted genes (H19, GTL2, MEST, and LIT1) and one repetitive element (LINE1). MAIN OUTCOME MEASURES: Methylation levels at CpG sites determined by bisulfite pyrosequencing. RESULTS: The H19 was significantly hypomethylated only in severe oligospermia compared with fertile controls, whereas other groups showed nonsignificant trends with overlapping distributions. In contrast, MEST was significantly hypermethylated in oligospermic, azoospermic, and VR groups compared with fertile controls. No significant differences were observed for GTL2, LIT1, or LINE1. CONCLUSION: The DNA methylation abnormalities in sperm are locus-specific and vary across infertility phenotypes. MEST alterations were consistent across groups, whereas H19 changes were limited to severe oligospermia. Similar methylation patterns in testicular sperm from azoospermic and VR groups suggest that epigenetic alterations may reflect the testicular environment or obstruction, or differences between testicular and ejaculated sperm.

Humans↗

Varicocele and male fertility.

Over the past 25 years the association of varicocele with male subfertility has been repeatedly demonstrated and the beneficial effect of varicocele ligation in infertile men with oligoasthenospermia has been documented. Since the precise mechanisms by which a varicocele affects spermatogenesis are still unclear, the proper approach to the management of "asymptomatic" varicoceles is controversial.

Adult↗

Effect of prolactin on the glycolytic metabolism of spermatozoa from infertile subjects.

The effect of prolactin on the glycolytic metabolism of spermatozoa from married infertile men whose semen had spermatozoal concentrations of less than 40 million/ml was studied. In a respirometry system, spermatozoa were incubated with L-U-14C-glucose as substrate. Glucose utilization and production of 14C-lactate by the spermatozoa in the presence of 100 ng of ovine prolactin were greater than in the absence of the hormone. The production of pyruvate was 2.5 times less than the production of lactate wehn spermatozoa were incubated in the absence of prolactin and 1.6 times less in the presence of prolactin. These results indicate that, in spite of having an increased glycolytic metabolism, spermatozoa from oligospermic men are are able to show additional glucose utilization in the presence of prolactin.

Adult↗

Artificial insemination homologous with oligospermic semen separated on albumin columns.

Semen samples obtained from 27 infertile men were separated on human serum albumin (HSA) columns prior to artificial homologous insemination (AIH). The columns contained either a single 7.5% HSA layer or two 17.5% and 7.5% HSA layers. Separated specimens were free of seminal debris, had significantly improved motility and progressive drive, and had a decreased percentage of abnormal forms. The total sperm count was also significantly decreased after separation, especially with the two-layer technique. No conceptions occurred in 21 couples when two-layer separation was used, but four pregnancies in 12 couples resulted from AIH with semen separated on the single-layer column. The mean total count of motile sperm obtained for AIH was 5 million with the two-layer and 31 million with the one-layer technique.

Adult↗

Serum gonadotropins and testosterone in infertile patients with varicocele.

Serum concentrations of gonadotropins and testosterone in 25 infertile men with varicocele were compared with those in control men and men with idiopathic oligo-azoospermia. No significant difference was found in values of serum follicle-stimulating hormone (FSH) (14.9 +/- 13.6 mIU/ml), luteinizing hormone (LH) (24.9 +/- 19.1 mIU/ml), and testosterone (5.0 +/- 2.1 ng/ml) when the group with varicocele was compared with either the control group (FSH, 7.0 +/- 3.2 mIU/ml; LH, 23.6 +/- 16.0 mIU/ml; testosterone, 5.3 +/- 1.8 ng/ml) or the group with idiopathic oligo-azoospermia (FSH, 23.0 +/- 22.69 mIU/ml; LH, 36.7 +/- 24.1 mIU/ml; testosterone, 5.31 +/- 2.3 ng/ml). However, compared with the control group, there was a significant elevation of serum FSH levels in patients with varicocele whose testicular biopsy score counts were between 1 and 4. The importance of preoperative determination of the serum FSH level is discussed.

Biopsy↗

Factors affecting sperm motility. II. Human sperm velocity and percentage of motility as influenced by semen dilution.

Spermatozoal velocity and percentage of motility were analyzed objectively with the multiple exposure photography method before and after specimens from fertile and infertile men were diluted in their own seminal plasma or normal saline. No significant change in percentage of motility was found in samples diluted up to 1:6 in both kinds of diluents. However, a significant relative increase (up to 25% of the original velocity) was found when a specimen was diluted with its own seminal plasma, and an even greater increase (up to 37% of the original velocity) was found when it was diluted with saline. Compared with undiluted specimens, there was no delayed effect on spermatozoal motility when semen was diluted with saline after up to 4 hours' incubation time. Contrary to the findings in animal and human semen described by others, there was no deleterious effect on sperm motility with this kind and rate of dilution and duration of time. The assumption that the increase in sperm velocity caused by dilution is not excitatory but is due only to a decrease of seminal fluid viscosity and a reduced number of spermatozoa which interfere with sperm free movement is discussed. We recommend evaluation of spermatozoal motility in diluted specimens in addition to evaluation of the original specimen in any routine semen analysis in order to determine true spermatozoal motility potential under optimal conditions.

Culture Media↗

Genetic causes and workup of male and female infertility. 1. Prenatal reproductive loss.

Studies show that the greatest check on human reproduction occurs prenatally in apparently fertile couples. Most chromosomally abnormal embryos are aborted spontaneously. This paper, to be published in three parts, reviews the major known anatomic, functional, genetic, and environmental causes of infertility and reproductive wastage. The second and third parts, to appear in succeeding issues, are concerned with chromosome abnormalities and congenital malformations in the period from birth to adult life and with the diagnostic workup of infertile men and women.

Abortion, Habitual↗

Association between seminal and serum iron parameters and male infertility: a systematic review and meta-analysis.

BACKGROUND: Iron is an essential trace element for normal spermatogenesis, yet excessive iron accumulation may impair male fertility. Preliminary studies imply a link between elevated iron levels and male infertility, but evidence remains limited without systematic quantitative synthesis. This metaanalysis assessed the association between iron concentrations and male infertility. METHODS: We systematically searched PubMed, CBM, CNKI and Cochrane Library. RevMan, Stata and R were used for data analysis. Randomeffects models pooled effect sizes, with forest and funnel plots generated to evaluate seminal and serum iron levels in male infertility. RESULTS: After screening studies published up to April 2025, a total of ten eligible articles involving 985 participants were finally included in this meta-analysis. Pooled results revealed that seminal and serum iron concentrations were notably higher in infertile males compared with fertile controls. Specifically, infertile men presented higher seminal iron levels (SMD&#x2009;=&#x2009;0.44, 95% CI: 0.12-0.76, P&#x2009;<&#x2009;0.05), as well as elevated serum iron levels (SMD&#x2009;=&#x2009;3.77, 95% CI: 1.68-5.87, P&#x2009;<&#x2009;0.05). The present results suggest that increased seminal and serum iron concentrations may be potentially correlated with male infertility risk.

Humans↗

Silent infection in male accessory genital organs and male infertility.

A silent infection of the male accessory genital organs was found in the semen of 78 patients (22,3%) of 350 infertile men. All the sperm characteristics (except agglutination) were significantly deteriorated in the infection group as compared to the sperm of 36 normal men. The volume was significantly larger than normal. In this group there was significant leukocytosis and, as a sign of prostatic hypofunction, reduced seminal acid phosphatase and citric acid activity. Chemotherapy for a period of two to four weeks improved leukocytosis and sperm transiently. Only acid phosphatase was normal three months after the treatment. Suggested reasons for the infertility of the silent infection group are: 1. hypofunction of the male genital organs, caused by a primary, strong infection suffered earlier. 2. The chronic, nonclinical infection of the male accessory genital organs, mainly as a complication of the primary infection. Chemotherapy for a period of four weeks seems to be too short to correct the silent infection as well as the infertility.

Acid Phosphatase↗

Studies on the immunogenicity of protamines in humans and experimental animals by means of a micro-complement fixation test.

A complement fixation study with human, monkey and rabbit sera, using purified sperm nuclear basic proteins as antigens, led to the following conclusions. (1) Protamines, the sperm-specific basic nuclear proteins, may be immunogenic in mammalians. (2) Antibodies detected in the indirect immunofluorescence test on human swollen sperm heads in sera from infertile and vasectomized men, are directed primarily against human protamines. (3) The results obtained suggested that differences in the immunization site and/or in the configuration of the immunizing protamine, may lead to the formation of antibodies directed against different antigenic determinants. Autoimmunity to protamines, following vasectomy or in infertile men, is accompanied by the formation of antibodies cross-reacting with common antigenic determinants present in protamines of other species. Induction of immunity to protamines by means of immunization with protamines-RNA complexes (in rabbits), or protamine-insulin complexes (in humans), leads to the formation of antibodies reacting more specifically with the immunizing protamine, showing only slight cross-reaction with other protamines. (4) The histone-like fraction present in mature human spermatozoa is composed mainly of histone fraction H2B.

Animals↗

The necessity for bilateral biopsy in oligo- and azospermia.

The 384 testicles from 192 infertile men were examined by bilateral biopsy. The main reason of this investigation was to see whether differences in the varying degrees of damage to the seminal epithelium existed in both testicles. Depending on the damage, the material was divided into five groups. The conclusion is, that the greater the degree of damage, the greater are the differences in the findings in both testicles. The left testis was more often and more strongly damaged than the right.

Adult↗

[Dynamic tests with GnRH, L-dopa, clomiphene, cyclophenyl, HCG and HMG in 98 cases of dysspermia due to a variety of causes].

Radioimmunological methods have been used to assay the plasma concentrations of gonadotropins, androgens (expressed as the sum of testosterone and dihydrotestosterone) and 17beta-oestradiol in 98 patients suffering from dysspermia of variable etiology, after stimulation with GnRH, Clomiphene, L-Dopa, Cyclophenyl, HCG in various dosage schemes, and HMG. Results show L-Dopa and HMG tests to be of little value in assessing the endocrine function in infertile men. They also confirm, in keeping with data found in the literature the usefulness of dynamic stimulation with GnRH, Clomiphene, and HCG for purposes of andrologic diagnosis. The GnRH proved useful for the distinction between primary and secondary hypogonadotropism as well as for assessing the therapeutic efficacy of releasing factors. The functional efficacy of the endocrine axis which is often impaired in patients with dysspermia can be evaluated by the Clomiphene test. In the small number of cases in which it was applied, Cyclophenyl brought about changes in gonadotropin concentration which require further study. The HCG tests, to be performed in patients with lower than normal testosterone plasma lavels, permits the discrimination between primary and secondary Leydig cell deficiencies as well as the assessment of interstitial tissue sensitivity to chorionic gonadotropin stimulation. Of the three dosage schemes (5000 IU, 7500 IU "step up", 10.000 IU) the last one is most suitable for clinical use.

Adult↗

Immunology and male infertility.

This article has attempted to review evidence that suggests that immune factors may be operative in a small but significant number of infertile men. Although our current understanding of the possible processes by which autosensitization to previously sequestered reproductive antigens occurs is incomplete, there are laboratory assays presently available that give an indication, but do not prove, that immune factors may be contributing to the infertile state. Continued research is needed to develop new assays and more purified sperm antigens, which might enhance our knowledge of the underlying immunoreproductive changes. Until these are available, the following procedures should be considered when investigating a patient with infertility of suspected immune origin. The patient's history should be taken, and a physical examination should be performed. A complete blood count, urinalysis, and complete semen analysis and culture should be taken. Next, in vivo cervical tests (Sims-Huhner) are performed, followed by sperm antibody assessment (serum, semen) and perhaps in vitro cervical mucus sperm assays (especially the crossed hostility test). After the tests have been completed, the following possibe treatments exist: 1. Treatment of underlying infections 2. Correction of obstructions 3. Corticosteroid (or testosterone?) therapy 4. Washed sperm insemination 5. First portion of fresh ejaculate insemination 6. Artificial insemination with homologous donor 7. Adoption.

Agglutination Tests↗

Immunity and male infertility.

This article has attempted to review evidence which suggests that immune factors may be operative in a small but significant number of infertile men. Although our current understanding of the possible processes by which autosensitization to previously sequestered reproductive antigens occurs is incomplete, there are laboratory assays presently available that indicate, but do not prove, that immune factors may be contributing to the infertile state. Continued research is needed to develop new assays and materials (especially purified sperm antigens) which might enhance our knowledge of the underlying immunoreproductive changes. Until these are available the outline below might be considered when investigating a patient with infertility of suspected immune origin.

Animals↗

Carcinoma-in-situ of testis in testicular feminization syndrome.

A light microscopical study of an excised testis from a 14 1/2-year-old girl with incomplete type of testicular feminization syndrome revealed a carcinoma-in-situ pattern in a part of the gonad. An identical histological pattern has repeatedly been demonstrated in infertile men who developed gross testicular germ cell tumours. It is suggested that germ cell carcinomas in patients with testicular feminization syndrome may be preceded by this characteristic intratubular germ cell abnormality.

Adolescent↗

On round-headed human spermatozoa.

In an infertile man and his only, likewise infertile, brother the sperm contained only round-headed spermatozoa. Electron microscopic examination of embedded ejaculate revealed a malformation, viz. absence of acrosomes in all the spermatozoa with consequent lack of normal development of the heads of the spermatozoa. Acrosomeless spermatozoa were also found in the testicular tubuli. No disturbance of the endocrine functions could be demonstrated. The blood cells were of normal male karyotype. Investigation of meiosis, on the other hand, showed rudimentary second division. Two other unrelated infertile men showed the same isolated disturbance in their spermiogram. Treatment with chlomiphene had no effect on the structure of the spermatozoa or on the infertility. The rare disorder, which seems to be a special syndrome, the first hitherto distinguishable among the various types of teratospermia, and its probable background are discussed.

Acrosome↗

Leydig cell density and function and their relation to gonadotropins in infertile oligospermic men with varicocele.

Circulating gonadotropin and testosterone levels in infertile men with varicocele and sperm counts of less than 10(7)/ml were correlated with testicular Leydig cell density and in vitro testosterone synthesis. A significant correlation was found between Leydig cell density and both plasma testosterone levels and in vitro testosterone synthesis. Luteinizing hormone (LH) levels paralleled the in vitro testosterone synthesis. Although in the majority of patients, in vitro testosterone synthesis and Leydig cell density were low, plasma testosterone and LH levels were within the normal range. The only abnormal circulating hormonal level was high follicle-stimulating hormone in the most severely oligospermic patients. No difference were found between the right and left testes with regard to in vitro testosterone synthesis or Leydig cell density, and no correlation with patient age or site or degree of varicocele could be demonstrated. These findings suggest that Leydig cell dysfunction was the mechanism responsible for the oligospermia and infertility of these patients.

Adult↗