Atlas of Clinical Andrology

Chapter 3. Semen and the functional anatomy of sperm

ANATOMICAL PARAMETERS

Spermatozoa are elongated cells consisting of a flattened head containing the nucleus and a tail containing the apparatus necessary for cell motility. The entire spermatozoon is covered by the plasmalemma or plasma membrane. The acrosome or acrosomal cap is a double-walled structure situated between the plasma membrane and the anterior portion of the sperm head. A neck connects the sperm head with its tail (flagellum), which is subdivided into the middle, main and end pieces (Figures 3.1-3.3).

Sperm head

The sperm head contains an oval flattened nucleus containing highly compact chromatin. The condensed chromatin comprises deoxyribonucleic acid (DNA) complexed to a special class of basic proteins known as sperm protamines. The chromosome number and hence the DNA content of the sperm nucleus is haploid or half that of somatic cells of the same species. The haploid sperm cell results from the meiotic cell divisions that occur during formation of sperm with X or Y chromosomes. Several methods have been applied to separate X and Y chromosomebearing sperm (Table 3.1).

The anterior end of the sperm nucleus is covered by the acrosome, a thin, double-layered membranous sac that is layered over the nucleus. This cap-like structure, which contains acrosin, hyaluronidase and other hydrolytic enzymes, is involved in the fertilization process. The equatorial segment of the acrosome is important because it is this part of the sperm, along with the anterior portion of the postacrosomal region, which initially fuses with the oocyte membrane during fertilization.

Sperm tail

The sperm tail is composed of the neck, middle, main and end pieces. The neck or connecting piece forms a basal plate that fits into a depression in the posterior aspect of the nucleus. The basal plate of the neck is continuous posteriorly, with nine outer coarse fibers that project throughout most of the tail. The region of the tail between the neck and the annulus is the middle piece. The central core of the middle piece together with the entire length of the tail constitutes the axoneme. The axoneme itself is composed of nine pairs of microtubules that are arranged radially around two central filaments. In the middle piece this 9+2 arrangement of microtubules is surrounded by the nine coarse or dense outer fibers that appear to be associated with the nine double fibers of the axoneme. The axoneme and associated dense fibers of the middle piece are covered peripherally by numerous mitochondria. The mitochondria are arranged in a helical pattern around the longitudinal fibers of the tail and supply the energy needed for sperm motility.

The main piece, which continues posteriorly from the annulus and extends to near to the end of the tail, is composed centrally of the axoneme and its associated coarse fibers. A fibrous sheath provides stability for the contractile elements of the tail.

The end piece, which is posterior to the termination of the fibrous sheath, contains only the central axoneme covered by the plasma membrane. The axoneme is responsible for sperm motility. The outer pairs of microtubules of the 9 + 2 pattern generate

Figure 3.1 Human sperm functional anatomy. (a) Two cross-sections of sperm head and connecting piece (neck). (b) Cross-section of a spermatozoon showing the head, middle and main piece in detail. (c) The nucleus containing genetic material (1) fits inside the head cap (2) like an acorn in its cup. The neck (3) contains two thick bundles of fibers which continue through the body of the middle piece (4) and tail (5). Spiral structure like binding threads coils around middle piece and tail

Figure 3.2 Functional ultrastructure of human sperm as shown by scanning electron microscopy after freeze drying. Note the characteristic pattern of the acrosome (a) and fibrils at the end of the tail (b). Courtesy of Zaneveld and Polakaski

the bending waves of the tail by a sliding movement between adjacent pairs. The protoplasmic or cytoplasmic droplet, which is usually detached from ejaculated sperm, is composed of residual cytoplasm. The principal chemical components of spermatozoa are nucleic acids, proteins and lipids.

Sperm morphology is examined by using eosin- nigrosin stain, and Wright’s and Williams’ stains. Stained slides are examined using a high microscopic magnification (400x). At least 150 spermatozoa are examined, with abnormal sperm being classified into five categories: tailless, abnormal heads, abnormal tail formations, abnormal tail formations with a proximal cytoplasm droplet, and abnormal tail formations with a distal droplet.

Globozoospermia

Globozoospermia is a unique condition in which sperm are abnormally shaped, have round-shaped nuclei, absence of an acrosome and aberrant structure of the middle piece. Intracytoplasmic sperm injection (ICSI) has been performed for individuals with this type of teratozoospermia. However, the egg activation rate after ICSI is very low and artificial activation is needed for successful fertilization. This fact suggests that lack of the acrosome or nuclear material might be the cause of low fertility in this type of infertility, as the sperm lacks the ability to initiate appropriate oocyte activation.

Sperm transport in female reproductive tract

Several endogenous and exogenous factors influence the pattern of sperm transport in the female reproductive tract from the site of ejaculation in the vagina to the site of fertilization in the oviduct (Figures 3.4-3.6). Sperm transport is under endocrine control, particularly during the early follicular, ovulatory and luteal phases (Figure 3.7).

Sperm-zona pellucida interaction

Capacitated sperm initially bind in a species-specific manner with the zona pellucida (ZP), an extracellular coat surrounding the egg. The sperm then undergo an exocytotic process, the acrosome reaction, because the sulfhydryl (SH) bonds are not oxidized until transit through the epididymis, testicular sperm DNA packaging is not complete, and their DNA may be more susceptible to assault. DNA integrity is determined by the modified alkaline single-cell gel electrophoresis (Comet) assay under yellow light to prevent further induced DNA damage. Fully frosted microscope slides are heated and covered with 100 μl of 1.0% normal melting point agarose in Ca2+- and Mg2+-free phosphate- buffered saline covered with a large coverslip. The slides are placed on a chilled metal tray and left at 4°C for >30 min to allow the agarose to solidify. The coverslips are removed and the slides immersed in a Coplin jar containing freshly prepared cold lysing solution. Testicular sperm from infertile men have more DNA fragmentation when incubated overnight after thawing than those assessed immediately after thawing. In contrast, DNA fragmentation in testicular sperm from fertile men is unaffected by the postcryopreservation incubation. The practice of incubating testicular sperm after cryopreservation damages their nuclear DNA, thus increasing the risk of selecting poor-quality sperm for ICSI (Dalzell et al., 2003).

Figure 3.3 (a) Sperm from the ejaculate of a normal man showing the characteristic racket shape of the head and long tail reaching 60 pm. Five cytoplasmic beads are seen in top and side views.The anterior portion of the head has a thick hood called the acrosome, while the posterior tapering portion has a thinner sheath called postnuclear cap. A transverse furrow marks the space between them.The middle piece of the tail just behind the head shows an undulating relief. This corresponds to the mitochondria that spiral around this portion of the tail. (b) Dimensions of human sperm, head, connecting piece and flagellum as seen by atomic force microscopy. From Barboza et al., 2004, with permission

BIOCHEMICAL PARAMETERS

Biochemical markers of sperm quality

Several biochemical markers have been used to evaluate human sperm maturity and function including sperm creatine-N-phosphotransferase or creatine kinase (CK), CK enzymatic active-site labeling and CK immunocytochemistry of individual sperm. Men with low sperm concentrations who have an increased incidence of infertility also show increased levels of sperm CK activity. This may be related to a defect of sperm development in the last phase of spermatogenesis, when excess cytoplasm is normally extruded and left in the adluminal area as residual bodies. Thus, sperm with a high CK content, an indication of surplus cytoplasm, have not completed cellular maturation (Huszar et al., 2003). There is also a second sperm maturation marker, which was initially thought to be a sperm-specific creatine kinase M-isoform and identified as the testis-expressed chaperone protein HspA2 (a member of the HSP70-2 family) that, along with the homologous hsc70, is synthesized in two waves of expression. The first wave occurs during meiosis, as HspA2 is part of the synaptonemal complex. The second wave of major expression occurs simultaneously with cytoplasm extrusion, in terminal spermatogenesis.

Table 3.1 Techniques employed to separate X and Y chromosome-bearing sperm

Technique

Results

Sedimentation of immobilized sperm on media

Insemination with sperm that had sedimented the greatest distance produced 70% females

Skimmed milk powder, glycine, sodium citrate, glycerol

Increase in number of male offspring when sperm from the top layers were used

Albumin column

Successful results with frozen bull sperm preselected on albumin column before cryopreservation

Velocity sedimentation

Sedimentation rates depend on size, density and shape of sperm. Cell size difference is predominant factor in separation of types; shape is usually the least important factor. Sperm heads have extremely aspherical shapes

Centrifugation through density gradients

Sperm separate according to their sedimentation rates by centrifugation through density gradients, provided the density of the gradient material is less than that of the sperm. The advantage is that the time required for separation is much shorter. Shorter time does not improve theoretical resolution of separation, because diffusion is insignificant

Motility and electrophoretic separation

Immotile sperm are electrophoretically attracted to the anode at neutral pH. When electrophoretic separation is under conditions consistent with sperm motility, sperm migrate to the cathode. Sperm are oriented by electric field and swim in the direction the head is facing. If negatively charged, sperm can be oriented so that the tail is facing the anode by virtue of its greater negative charge density, and their intrinsic motility is greater than the electrophoretic mobility

Isoelectric focusing

Separation performed in columns with the fluid stabilized using density gradients. Sperm layered on, or suspended in, this solution migrate electrophoretically until reaching an isoelectric point

H-Y antigens

Sperm treated with H-Y antisera. Insemination with mouse sperm treated with antisera to a Y-linked histocompatibility antigen produced 45% males compared with 53% for controls

Flow sorting by DNA content

Y chromosome-bearing sperm sorting is 72-80% successful. Disadvantages: low sorting rate and lack of sperm viability after sorting

Sephadex column

Approximately 70% (65-85%) of X chromosome-bearing sperm can be found in certain fractions of the filtrate when sperm are placed on top of a column of Sephadex



Seiwa (1993a, b, 1994, 1995a, b, 2000) conducted intensive investigations of in vitro sperm migration using various chemoattractants such as heparin, beta endorphin and sex steroids.

Sperm apoptosis

Degeneration of germ cells occurs via apoptosis. During apoptosis, an endogenous endonuclease is activated; this endoendonuclease cleaves DNA between nucleosides, fragmenting DNA into multiple 180-200 base-pair fragments that appear as a characteristic DNA ladder on agarose gel electorphoresis. Germ cell apoptosis occurs spontaneously and is induced by exposure to hypothermia (rats) and to chemotherapeutic agents and by reactive oxygen species (ROS). There is a significant difference between apoptotic cells after swim-up and Percoll™ gradient, with PureSperm at 24 hours of incubation.

Figure 3.4 Endogenous and exogenous factors affecting sperm transport in female reproductive tract

Figure 3.5 Secretory cells of the oviduct provide a physiological milieu for sperm capacitation and fertilization

Apoptosis is present in seminal samples. The percentage of apoptotic cells differs significantly between methods of purification, swim-up and Percoll gradient, with PureSperm. PureSperm has a significantly lower percentage of apoptotic cells. Further studies are necessary to determine the role of apoptotic cells and the mechanism by which different culture media affect sperm DNA integrity (Benitz et al., 2002).

Sperm function test (Table 3.2)

Sperm penetration

Sperm films on microscopic slides are examined by phase-contrast microscopy at 400x magnification. The sperm penetration index is evaluated by counting the number of decondensed (swollen) sperm heads with an adjacent or closely associated sperm tail within the cytoplasm, as follows:

Figure 3.6 Sperm plasma membrane: (I) non-motile lipoproteins with oligosaccharide chains; (2) motile lipoproteins; (3) transmembrane proteins; (4) lipid bilayer; (a) spectrin; (b) actin; (c) binding protein. From Calamera (1998), with permission

Hemizona binding assay

Sperm are incubated with oviductal cells and conditioned at 37°C under 5% CO2 in air for 24 h. The effect of the conditioned media on zona pellucida- binding capacity is evaluated as follows:

MOLECULAR PARAMETERS

Sperm immobilizing proteins

Extensive investigations have been conducted to develop an effective non-invasive contraceptive agent that can block or retard sperm motility. Lysenin, a protein purified from the coelomic fluid (CF) of an earthworm, Eisenia foetida, immobilizes and kills the sperm of mammals including man. However, lysenin is not suitable because its addition to ex vivo blood destroys mammalian erythrocytes and its intravenous injection instantaneously kills rats/mice. Mukherjee et al. (2003) isolated a novel protein, immotilin, from CF of an earthworm, Metaphire peguana, that instantly immobilizes and kills human and other mammalian sperm without affecting other cells. Immotilin, a 47-KS protein, therefore, shows great promise as a non-invasive antifertilizing agent. Heat treatment of the CF destroys its sperm immobilizing activity, indicating that the active component may be a protein.

Based on its immobilizing activity, the bioactive molecule from the CF was purified to homogeneity by using gel-permeation chromatography and ion exchange chromatography on a high-pressure liquid chromatography (HPLC) SpherogelTM TSK DEAE column (Merck). Considering the remarkable sperm immobilizing activity of the purified protein, this protein has been called immotilin. Taking the crude extract as the initial step of purification, the purification was 106-fold.

A relationship between low acrosin activity and reduced fertilization rate has been demonstrated; the incidence of abnormal acrosin activity in male patients with unexplained infertility was 19%. The diminished activity apparently was not the result of a decrease in proacrosin/acrosin acrosomal levels, but rather of alterations in the proenzyme activation. By using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis, no changes were detected in the nucleotide sequence around the active site of the sample (Mukherjee et al., 2003). Nucleotide sequence analysis on the sequence encoding human proacrosin and the 5'UTR region in genomic DNA from these patients may reveal alterations that could explain abnormal protein function.

a6β1 Integrin as sperm quality marker

The sperm penetration assay with zona-free hamster eggs is often used as an in vitro prognostic test of male infertility. However, it is not known whether a low rate of binding and/or penetration is the result of poorly induced acrosomal reaction or impaired binding. Evaluation of the acrosomal status of sperm is an important task within the diagnostic work-up of male fertility to predict fertilizing potential. Expression of a6β1 integrin was significantly reduced in sperm obtained from subfertile men. Only 35-40% of sperm from fertile men showed a positive reaction to a6β1 antibody. Samples with a high rate of acrosomal reaction showed a high level of expression of a6β1 and maximum binding to oocyte in an in vitro binding assay. a6β1 Integrin may be used as a clinical marker to evaluate sperm quality.

Biochemistry of sperm flagellum

Several biochemical components have been identified in the flagellum of spermatids and spermatozoa in mammals. They increase the future probability of determining the genetic pathways controlling flagellar morphogenesis (Figures 3.8 and 3.9). The recent findings of flagellar anomalies in Ube2b-deficient mice, associated with a better understanding of flagellar elements, could help to identify candidate flagellar proteins as targets of UBE2B. Additionally, Ube2b-null mice are an unexpected and precious murine model for a similar human sperm pathology.

Figure 3.7 (a) Endocrine control of sperm transport in various segments of female reproductive tract. (b) Pattern of sperm transport during early follicular, ovulatory and luteal phases of the menstrual cycle. FSH, follicle stimulating hormone; FRF, FSH-releasing factor; LH, luteinizing hormone; LRF, LH-releasing factor

Reactive oxygen species

Sperm generate reactive oxygen species (ROS), which play a physiological role in signaling the events controlling sperm capacitation, sperm hyperactivation, acrosome reaction and sperm-egg fusion. However, excessive generation of ROS by defective sperm or contaminating leukocytes exerts a detrimental effect on sperm function. Hydrogen peroxide is the primary ROS responsible for such molecular changes and membrane lipid peroxidation is an important mechanism of action. Semen contains antioxidants, including ascorbic acid, tocopherol, β-carotene, catalase, glutathione peroxides and superoxide dismutase, that balance lipid peroxidation and prevent excessive peroxide formation (Aitken et al., 1998a; Aurech et al., 1997). Glutathione peroxide functions in the aqueous phase of cells and vitamin E is stored and functions in the lipid portions of cell membrane parts. A possible relationship exists between the intoxicative function of selenium and cytochromes and oxygen metabolism. Selenium also has a role in electron transfer in the cytochrome system.

DYNAMICS OF SPERM MOTILITY

Initiation of sperm motility has been associated with protein phosphorylation as well as with changes in intracellular calcium and pH. Several proteins become phosphorylated at the time when sperm start moving actively. The majority of these proteins are phosphorylated on serine or threonine residues and their phosphorylation is cAMP dependent. Most studies have focused on the initiation and activation of sperm motility. Motility assessment involves subjective estimation of the viability of sperm and the quality of the motility. Light microscopic analysis of sperm is most commonly used. Evaluation of sperm motility is conducted with raw and diluted semen. Evaluation of raw semen is an indicator of sperm performance in their own accessory gland fluid. Measuring motility in the raw form can be hampered by higher sperm concentrations, making it difficult to discern individual motility patterns. To overcome this limitation, an aliquot of semen should be diluted to a concentration of 25 x 106 sperm/ml) in a good-quality diluent.

Sperm motility is extremely susceptible to environmental conditions (such as excessive heat or cold), so it is necessary to protect the semen from injurious agents or conditions prior to analysis. To further enhance the reliability of motility estimation, experienced personnel and a properly equipped microscope are required. A drop of diluted semen is placed on a glass slide and covered with another slide; it is then observed using a microscope with a built-in stage warmer and phasecontrast optics. Magnification of 200-400 x is generally used to estimate sperm motility.

Various patterns of sperm motility have been established by the World Health Organization (WHO) and different governmental agencies (Tables 3.3 and 3.4).

Sperm hyperactivated motility

Hyperactivated motility is characterized by vigorous, large-amplitude, whiplash-like flagellar beats with the sperm heads tracing erratic trajectories (Figure 3.10). Sperm hyperactivity is critical for binding with the oocyte and subsequent fertilization. Hyperactivity can be assessed in a computer-assisted motion analyzer (Hamilton-Thorn v. 10.8, Beverly, MA) using a 20-μm chamber at 37°C. The required settings are frames, 30; frame rate, 60 Hz; minimum contrast, 85; minimum cell size, 2 pixels; and minimum static contrast, 30.The following parameters are used to define hyperactivation: curvilinear velocity (VCL) > 100 μm/s, linearity of forward progression (LIN) < 65% and amplitude of lateral head displacement (ALH) >7.5μm.

Figure 3.8 UBE2B and mammalian flagellum morphogenesis. Possible involvement of UBE2B in the assembly of flagellar cytoskele- tal structures, as suggested by the murine Ube2b phenotype, is shown.The gray arrows represent the stages of assembly of flagellar structures. First,the distal centriole gives rise to the axoneme (black),and then the structure of the longitudinal column (LC) appears on double fibers 3 and 8 (white circles), where the LCs of the fibrous sheath (FS) are finally assembled. A, axoneme; C, centrosome; As, anchorage structures; ODFs, outer dense fibers. From Escalier, 2003, with permission

VCL is the rate of travel of the centroid of the sperm head over a given period of time. Straight-line velocity (VSL) is the straight-line distance between the first and the last centroid positions for a given period of time. Average path velocity (VAP) is the spatial average path that eliminates the wobble of the sperm head. LIN is the ratio of VSL to VCL.

Inhibitors of sperm motility

Inhibitors of sperm motility are of great clinical significance in the development of male contraceptives. Among the selective protein tyrosine kinase inhibitors, genistein is the most active and consistent, inhibiting sperm tyrosine kinase activity. This involves inhibition of sperm mobility/motility patterns such as VCL, ALH and hyperactivation motility patterns. Other kinase inhibitors decrease motility characteristics to a variable extent and have different effects on phosphorylation parameters (Figure 3.11). In general, they decreased phosphorylation of two proteins (83 and 54 kDa) present in whole sperm extracts, and two sets of proteins of low (39-49 kDa) and medium (55-87 kDa) molecular weight present in the Triton X-100-solubilized sperm protein fraction (Bajpai et al., 2003).

Figure 3.9 A molecular model illustrating the structural association of Fer kinase with the known adherens junction (AJ) structures at the site of ectoplasmic specialization.The three known AJ structural protein complexes at the site of ectoplasmic specialization in the testis are the cadherin-catenin complex, nectin-afadin-ponsin complex and a6β1 integrin-laminin complex.The functional laminin, the receptor for a6β1 integrin, consists of three chains,yet laminin y3 is the only known non-basement-membrane laminin in the testis;the other two chains remain to be identified. Based on the results presented by Chen et al. (2003), it is apparent that Fer kinase is associated with the N-cadherin- based cadherin-catenin complex and interacts with other AJ-associated signaling molecules. Also shown (lower panel) are the structural similarities between Fer kinase and Fer T kinase. CBD, catenin-binding domain; CC, coiled-coil domain; FCH, Fps/Fes/Fer/CIP4 homology;JMD, juxta membrane domain; SH2, Src homology 2 domain; U, unique Fer T sequence, 44 amino acids. From Chen et al., 2003, with permission

Sperm motility and metal chelators

The kinetic energy required for sperm motility is generated in the axoneme. The outer dense fibers extend along 60% of the length of the main piece of the sperm tail, consist of a few structural proteins and comprise medulla and cortex. Immunoelectron microscopic studies in the bull have shown an 84-kDa protein to be localized over the whole structure. This protein is apparently a basic structural element of the outer dense fibers. The results imply that chelators can eliminate at least some part of the zinc from the flagellum. This zinc elimination appears to lead to comparable changes of the outer dense fibers as seen in vivo during epididymal maturation, finally resulting in improved motility (Wroblewski et al., 2003).

SEMEN TECHNOLOGY

Semen analysis

Assisted reproductive technology (ART) requires semen to be processed to obtain a sample with progressively motile (types A and B) and morphologically normal sperm (strict morphology), after the elimination of undesired elements (i.e. round cells, morphologically abnormal sperm and sperm with abnormal or no motility (types C and D)) and prostaglandin. Three main techniques are used to process semen samples in the laboratory: gradients, migration and filtration. These procedures are applied to generate post-processing samples containing a high concentration of morphologically normal sperm with good progressive motility. There is positive correlation between these parameters and the rate of clinical pregnancy obtained by intrauterine insemination (IUI) and in vitro fertilization (IVF).

Figure 3.10 Different patterns of sperm motility, sperm tail beating and head-centroid trajectories: (a) non-hyperactivated; (b) hyperactivated. This is a method of discriminating between non-hyperactivated and classical hyperactivated motility patterns in sperm using computerized analysis of sperm motility and kinematics

The sperm recovering efficiency (SRE) model is an equation that can be used to quantify objectively the technical skill of individual operators processing semen specimens in an andrology laboratory. Additionally, this equation can be used to compare different semen processing methods and protocols. The model integrates the semen parameters of initial sperm concentration, motility and morphology, with final sperm recovery to produce a unique number that can be used to compare results.

Semen analysis technology

The value of sperm morphology as a predictor of a man’s fertilizing potential is challenged because of the use of different classification systems and numerous technical variations, including differences in the methods used to prepare and stain specimens, differences in proficiency among technicians and inherent differences in classification criteria and methods. Careful determination of sperm concentration, movement and morphology requires a great deal of technical expertise and procedural care in semen handling and evaluation, e.g. the installation of meticulous quality control (QC) programs and technician proficiency testing (PT) systems. A continuous QC program can be initiated only after intensive training, because baseline values at the onset of the QC program serve as an internal reference value (Franken et al., 2003).

Leukospermia

Routine application of antibiotics for leukospermia may have a negative impact on semen parameters as well as increasing the possibility of inoculating the reproductive tract of the female partner with antibiotic-resistant bacteria. The presence or absence of bacteriospermia or leukospermia do not correlate with each other. Leukospermia has been shown not to correlate with semen parameters. Staphylococcus species were the most common isolates and did not correlate with semen parameters or leukospermia. Streptococcus viridians and Enterococcus faecalis were the next most common isolates and were associated with statistically significantly poorer semen quality (Rodin et al., 2003). Leukospermia is a poor marker for either bac- teriospermia or impaired semen quality. Staphylococcus species are commonly isolated but appear to be innocuous. Streptococcus viridians and Enterococcus faecalis are associated with poorer semen quality and may warrant treatment.

Figure 3.11 (a) Effect of kinase inhibitors on hyperactivated sperm motility. Washed sperm were incubated with or without kinase inhibitors for 6 h in Ham’s solution at 37°C in 5% CO2. Motion parameters were assessed using the Hamilton-Thorn Motion Analyzer (v. 10.8). Data are expressed as percentages of the control (without inhibitors) indicated by the dashed line. (b) Effect of kinase inhibitors on the incidence of immunoreactive sperm tails after a 6-h incubation in Ham’s solution at 37°C in 5% CO2. Sperm were fixed and permeated with methanol and labeled with phosphotyrosine monoclonal antibody and fluorescein isothiocyanate (FITC)- conjugated anti-mouse IgG (Bajpai et al., 2003).Wilcoxon’s signed rank test was used to analyze the data (vs. control). *p < 0.0001; **p < 0.05; Gen,genistein; Tyr, tyrphostin, Erb, erbstatin; Her, herbimycin A; Sta, staurosporin

Azoospermia and oligozoospermia

Azoospermia and oligozoospermia are associated with a wide variety of genetic anomalies. Chromosomal anomalies are more frequent in infertile men compared with fertile men, with a frequency of 2% of all men attending infertility clinics. In azoospermia, the frequency rises to 15%, including about 13% with a 47,XXY chromosome constitution. The remaining azoospermic cases are characterized by specific anomalies which include other numerical structural anomalies, such as reciprocal and Robertsonian translocations, inversions, ring chromosomes, aneuploidies and supernumerary chromosomes. Congenital bilateral absence of the vas deferens (CBAVD) leading to obstructive zoospermia in healthy males is a relatively frequent cause of male infertility, occurring at the rate of 1-2% of cases with male sterility and > 6% of cases with obstructive zoospermia. Most men with CBAVD have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, with an increased risk of carrying the 5T variant.

Sperm chromosome aneuploidy/globozoospermia

Globozoospermia (round-headed sperm) is a very rare condition observed in < 1% of infertility patients. The sperm lack an acrosomal cap. Pregnancy is rare even with application of ICSI. It would

appear that other abnormalities may coexist with the lack of an acrosome. An increased frequency of sperm chromosome aneuploidy might be associated with globozoospermia and, therefore, might be responsible for the poor pregnancy prognosis. Aneuploidy for chromosome 15 has been implicated. There is a remarkable increase in the frequency of chromosome 15 aneuploidy in globo- zoospermia patients who have subsequently fathered a trisomy 15 conceptus. Little is known about the frequency of chromosome 15 aneuploidy in these infertile men. An increased frequency of XY disomy, which is the most common type of chromosome abnormality, has been observed in the sperm of infertile men (Martin et al., 2003).


If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!