EAU guidelines on ejaculatory dysfunction.
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Ejaculation↗
Biomedical subjects
T Hargreave
Publications and source records attributed to T Hargreave.
Y-chromosomal DNA haplotypes in infertile European males carrying Y-microdeletions.
We have determined Y-chromosomal DNA haplotypes in 73 infertile European males carrying Y microdeletions and compared them with the haplotypes of 299 infertile males lacking microdeletions. Chromosomes were typed with a set of 11 binary Y markers, which identified 8 haplogroups in the sample. Haplogroup frequencies were compared between 3 microdeletion classes and the non-deleted infertile males. Deletions arise on many different haplotypic backgrounds. No statistically significant differences in frequency were seen, although the small number of AZFa deletions lay predominantly on one branch of the Y haplotype tree.
DNA↗
Genetically determined male infertility and assisted reproduction techniques.
This is a review of the common chromosome and genetic disorders associated with male infertility that need to be considered by the clinician and the couple in the context of treatment. Until recently the most relevant disorders have been those inherited from parents, however, with the advent of technologies enabling recovery of sperm from the testicle in men with severely damaged spermatogenesis there is increased interest in those genetic abnormalities that may occur in mitosis and meioses. It is likely that over the next ten years there will be increasing focus on this aspect of male fertility genetic disorders. This article needs to be read in conjunction with the specific in depth reviews in this journal edition.
Aging↗
The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences.
The position of deletion breakpoints in a series of four AZFa male infertility patients has been refined using new markers derived from BAC clone DNA sequence covering the AZFa male infertility interval. The proximal half of the AZFa interval is occupied by pseudogene sequences with homology to Xp22. The distal half contains an anonymous expressed sequence tag (named AZFaT1) found transcribed in brain, testis, and skeletal muscle and the DFFRY and DBY genes. All the patients have AZFaT1 and DFFRY deleted in their entirety and three patients additionally have DBY deleted. The three patients with AZFaT1, DFFRY, and DBY deleted show a severe Sertoli cell only syndrome type I phenotype, whereas the patient that has retained DBY shows a milder oligozoospermic phenotype. The expression of DBY in a cell line from this latter patient is unaltered; this shows that it is the loss of genes lying within the deletion that is responsible for the observed oligozoospermia. RT-PCR analysis of mouse testis RNA from normal and XXSxr(a) mice (devoid of germ cells) has shown that Dby is expressed primarily in somatic cells and that the level of expression is unaltered during germ cell differentiation. This contrasts with Dffry where no transcripts are detectable in XXSxr(a) mouse testis and expression occurs specifically in testis mRNA in a germ cell dependent fashion.
Adult↗
Varicocele: does treatment promote male fertility?
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Adolescent↗
Understanding the genes involved in spermatogenesis: a progress report.
OBJECTIVE: To review the current literature on genes known to affect fertility in the human and mouse. DESIGN: A literature review was performed and key articles were chosen for focus in the areas of genes with effects only on spermatogenesis and oogenesis, with an emphasis on Y-chromosome-encoded gene families and spermatogenesis. In addition, studies describing genes deleted in transgenic mice were incorporated. RESULT(S): Several gene families on the Y chromosome are implicated in spermatogenic failure, but the link between the genetic lesion and the resulting defect is unclear. Many mouse genes involved in repair and DNA damage monitoring have specific effects on gametogenesis in and around meiosis. CONCLUSION(S): Many genes are involved only in gametogenesis, and some of these are beginning to be understood in terms of their functions. An even larger number of genes is required for gametogenesis, and other functions and mouse models give insights important for human disease.
Animals↗
Male fertility disorders.
Effective treatments for extreme oligozoospermia include in vitro fertilization, recovery of sperm through epididymal sperm aspiration or testicular sperm aspiration, and direct injection of sperm through intracytoplasmic sperm injection. The clinical evaluation of and treatment options for male patients with fertility disorders are detailed in this article.
Female↗
P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population.
Only three mutant cystic fibrosis (CF) alleles have to date been established as conferring a dominant mild effect on affected subjects who are compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated) with this allele, the average age at diagnosis was 22.5 +/- 11.3 years. None of the cases had consistently raised sweat chloride concentrations, the average value being 57 +/- 9 mmol/l; 77% of the patients were pancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849 + 10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be confirmed other than by DNA typing.
Adolescent↗
Extracellular organelles (prostasomes) are immunosuppressive components of human semen.
Numerous reports have ascribed immunosuppressive activity to human seminal plasma and there is growing agreement that much of this activity can be accounted for by the very high levels of E series prostaglandins present (up to 300 microM 19-hydroxy prostaglandin E). However not all suppressive activity is due to prostaglandin since several reports have appeared of high molecular weight active substances and we have found that stripped seminal plasma is still effective in inhibiting the mitogen-induced proliferation of lymphocytes. In this study such immunosuppressive activity has been separated by molecular size fractionation and the activity has been found to be particulate and corresponded to the previously reported prostasomes. These are trilaminar to multilaminar vesicles (150 nm diameter) which are secreted by the prostate. Pure preparations of prostasomes inhibited mitogen-induced lymphoproliferation in a dose-dependent manner with a concentration of prostasomes equivalent to 40% of that seen in seminal fluid giving 69% suppression of thymidine incorporation. The suppressive activity survived boiling and therefore was unlikely to be due to enzymatic action associated with these organelles. Interaction with the accessory cells, involved in full development of the lymphoproliferation induced by mitogen, was indicated and this possibility was supported by the demonstration of a direct effect of prostasomes on macrophage function using a mouse macrophage cell line. The prostasomes in semen may play a complementary role to the prostaglandins in neutralizing the immune defences of the female reproductive tract. This combination would allow the alloantigenic spermatozoa the best chance of achieving fertilization, but at the same time leave the recipient open to any infection present in the semen.
Analysis of Variance↗
Analysis of sperm function in globozoospermia: implications for the mechanism of sperm-zona interaction.
The globozoospermic condition has provided a unique opportunity to determine how the abnormal mitochondrial organization and acrosomal loss associated with this syndrome, influence sperm function. Despite the abnormal midpiece architecture, the movement characteristics of the spermatozoa, in terms of the curvilinear, path, and progressive velocities, amplitude of head displacement, and hyperactivation were all within the normal range. Similarly, the behavior of the spermatozoa on Percoll gradients was normal, although the capacity of the isolated fractions to generate reactive oxygen species was negligible. Of particular significance was the fact that the globozoospermic spermatozoa were incapable of sperm-oocyte fusion or binding the human zona pellucida, even after an intracellular calcium signal had been generated with the ionophore A23187. The sudden induction of sperm-zona interaction could, however, be achieved by the use of a ferrous ion promoter system to induce limited lipoperoxidation. This result demonstrates that the enhancing effect of peroxidation on sperm-zona adhesion involves a direct action on the properties of the sperm-plasma membrane, rather than an indirect consequence of acrosomal damage and acrosin leakage. Such findings emphasize the value of specific teratozoospermic conditions, such as globozoospermia, in dissecting the mechanisms that regulate human sperm function.
Adult↗
Analysis of human sperm function following exposure to the ionophore A23187. Comparison of normospermic and oligozoospermic men.
Time exposure photomicrography and interspecific in vitro fertilization techniques have been used to compare the responses to the divalent cation ionophore A23187 of spermatozoa from normal fertile and oligozoospermic men. The fertilizing capacity of spermatozoa from the fertile controls produced a bell-shaped dose response curve when assessed in the presence of ionophore. The optimal responses occurred in the presence of 50 and 100 microM A23187. At this concentration, a mean penetration rate of about 75%, in association with multiple polyspermy, was observed without significant changes in motility patterns. At higher doses of A23187, there was a decline in fertilization rates, an independent reduction in sperm motility, and a significant decrease in the amplitude of lateral sperm head displacement. In contrast to the fertile controls, spermatozoa recovered from patients with oligozoospermia failed to exhibit a significant change in their fertilizing potential following exposure to A23187. Calculations based on the Poisson distribution theory indicated that this lack of responsiveness was not related to any differences in the motility of the spermatozoa from the oligozoospermic patients compared to the controls. These results suggest that calcium ionophores may be of value in providing a rapid and sensitive indicator of the functional competence of human spermatozoa, which circumvents problems concerning the rate and efficiency of sperm capacitation encountered with conventional protocols.
Adult↗