References

Abeyta M, Clark AT, Rodriguez R et al. (2004) Unique gene expression signatures of independently-derived human embryonic stem cell lines. Human Mol Genet 13, 601-608. Agulnik AI, Zharkikh A, Tong HB et al. (1998) Evolution of the DAZ gene family suggests that Y-linked DAZ plays little, or a limited, role in spermatogenesis but underlines a recent African origin for human populations. Human Molec Genet 7,1371-1377. Asaoka-Taguchi M, Yamada M, Nakamura A et al. (1999) Maternal Pumilio acts...

Structure and function of mammalian spermatozoon

To fully appreciate the mechanism of sperm biogenesis (i.e. spermatogenesis and spermiogenesis), it is important to briefly review the subcellular structure and function of the mammalian spermatozoon (reviewed by Fawcett, 1975). The spermatozoon (Fig. 1.2) is composed of a sperm head and sperm tail or flagellum. Both sperm head and sperm tail are covered by sperm plasma membrane, or plasmalemma. The rodent sperm head is hook-shaped (falciform), while ungulate, carnivore and primate sperm heads...

Changes to sperm structure during fertilization

The elaborate process of spermatogenesis and spermiogenesis, in particular, results in the formation of specialized sperm accessory structures that afford the spermatozoon its motility and protect it from the environment encountered during sperm transport through the female reproductive tract and interaction with egg vestments. To achieve motility, the spermatozoon must sacrifice most of its organelles and most of its cytoplasmic volume. In a complementary manner, the oocyte cyto-plasmic volume...

Sperm chromatin structure and fertility

Before discussing DNA damage as it relates to sperm chromatin structure we will briefly review those aspects of sperm chromatin, both known and suspected, that pertain to this discussion. During spermiogenesis the haploid sperm chro-matin undergoes one of the most significant changes known in biology. All of the histones are replaced first by transition proteins, then by protamines (Meistrich et al., 2003). This condenses the sperm DNA so tightly that it is resistant to mechanical stresses such...

Kallman syndrome 1 30000

Idiopathic hypogonadotropic hypogonadism (IHH) or Kallman syndrome is characterized by hypogonadism. Most patients experience a delay in puberty although those with less severe defects may present with only infertility. Other findings include anosmia, small testes and occasionally renal agenesis, bimanual synkinesia, cleft lip and dental agenesis. When anosmia is not present, the condition is termed IHH. Testicular biopsies display a wide range of findings from germ cell aplasia to focal areas...

Male fertility marker genes

Mature mammalian spermatozoa require a post-testicular maturation process, including their exposure to the specific microenvironment provided by the epi-didymis. Therefore, ICSI fertilisation rates with testis-extracted spermatozoa (TESE) are usually lower then when mature spermatozoa isolated from the patient's ejaculates are used (Tournaye, 1999 but see also Bukulmez et a .,2001).Also,a reduced implantation rate has been reported for ICSI cycles using testicular sperm compared with those...

Prognosis for AZF deletions testis sperm retrieval and intracytoplasmic sperm injection results

Patients with AZFc deletions carry the best prognosis for finding sperm during testicular sperm retrieval procedures performed for intra-cytoplasmic sperm injection (ICSI). Although results vary by center experience and retrieval method, approximately 50-55 of AZFc deleted men will have testis sperm available for ICSI (Hopps et al., 2003 Krausz et al., 1999). In patients with complete AZFa or AZFb microdeletions, a negative prognosis for sperm retrieval is the expectation, but this is based on...

Prognosis for AZF deletions testis histological findings

When analyzing the testis histology associated with Yq microdeletions, it appears that several general patterns exist (Vogt et al., 1996). Complete AZFa deletions are associated with germ cell aplasia or Sertoli cell-only histology (Type I). Complete AZFb deletions are generally associated with maturation arrest at the primary spermatocyte (early) or spermatid (late) stages. As might be expected, partial AZFa or AZFb deletions have a mixed testis phenotype. AZFc deletions are associated with...

Spermatogenesis

Spermatogenesis Waves

The purpose of spermatogenesis is to establish and maintain daily output of fully differentiated spermatozoa that in eutherian mammals ranges from > 200 million in man to 2-3 billion in bull. This massive sperm production requires the unique architecture of the seminiferous epithelium, a self-contained system that is well-isolated from the blood stream, allowing only selective uptake of paracrine factors. Also unique to the reproductive system and germ line is that it is relatively quiescent...

The extended semen evaluation

Semen Analysis Germ Cells

If abnormalities are found during the basic investigation, or if the couple is diagnosed with unexplained infertility, the work-up should progress to the examination of specific structural features, biochemical characteristics and sperm functions. Sperm from subfertile men often contain multiple structural and biochemical alterations. Anatomically they can be divided into membrane alterations, that can be assessed, for example, by tests of resistance to osmotic stress, translocation of...

Detection of ROS in the male germ line

Given the importance of ROS and the apparent vulnerability of spermatozoa to oxidative stress, it might be anticipated that sophisticated methods have been developed to detect these intermediate oxygen metabolites for diagnostic purposes. In fact, this area has been severely compromised by the absence of sensitive, accurate analytical methods capable of confirming the presence of specific ROS in biological systems. The most commonly used method for detecting ROS in an andrological context is...

Introduction

From mouse and Drosophila knock out experiments it has been deduced that the products of more than 3000 genes are involved in the genetic control regulating the expression of male (and female) fertility (Cooke and Saunders, 2002, Hackstein et al., 2000 Matzuk and Lamb, 2002). In human, the molecular identification of male fertility genes is hampered by the fact that human is not an experimental species. An infertile man is only recognised after the couple desiring for a child has asked for some...

Prognosis for AZF deletions offspring

It has been shown that men with AZF deletions who conceive with IVF-ICSI will pass on the Yq deletion to male offspring (Mulhall et al., 1997, Oates et al., 2002). Thus far, children conceived with an affected father are somatically healthy. However, male offspring would be expected to show similar spermatogenic deficiencies that currently exist in Yq-deleted men. Given that genetic mutations can remain stable or increase in extent as a species evolves, it is likely that male offspring of...

Single gene defects in infertile men

Besides the AZF genes in Yq11, it has been predicted from mouse knock-out models that numerous autosomal and X-chromosomal genes also expressed in the human male (and female) germ line can cause infertility (Cooke and Saunders, 2002 Matzuk and Lamb, 2002). However, although most of their human homologues are known, it is often unclear whether and how these genes are also functional in the human male germ line. Only the genes functioning for meiosis seem to be functionally conserved in the...

Impact of oxidative stress on spermatozoa

The clinical significance of oxidative stress in the aetiology of defective sperm function was first indicated by Thaddeus Mann and colleagues at the University of Cambridge, 25 years ago (Jones et al., 1979). These authors observed a correlation between the lipid peroxide content of human spermatozoa and severe motility loss. This relationship between motility loss and oxidative stress is striking and has been repeatedly demonstrated in independent studies (Aitken and Clarkson, 1988 Aitken and...

Acknowledgments

Richard Oko, Dr. Ron Tovich and Dr. Antonio Miranda-Vizuete for the permission to include data from our collaborative research projects. We thank Kathryn Craighead for proofreading and Miriam Sutovsky and Nicole Leitman for the assistance with figure preparation. This work was in part supported by USDA-NRI Award 02069 and funding from the F21C program of the University of Missouri-Columbia. Agell N and Mezquita C (1988) Cellular content of ubiquitin and formation...

Sperm apoptosis

The TUNEL assay described above was originally used to measure apoptosis in somatic cells. The association of positive TUNEL assay results (i.e., DNA strand breaks) in ejaculated sperm led to the idea that mature sperm cells may possess the ability to go through apoptosis. That this is a controversial proposal is not surprising - the sperm cell is the protector and deliverer of the embryo's paternal compliment of DNA the last thing one expects are apoptotic nucleases to be present. However,...

Klinefelter syndrome incidence 1 500

This disorder is the most common genetic cause of azoospermia, accounting for 14 of cases. It is classically associated with a triad of findings small, firm testes, azoospermia and gynecomastia. Other features of the syndrome are increased height, decreased intelligence, varicosities, obesity, diabetes, leukemia, increased likelihood of extragonadal germ cell tumors and breast cancer (20 X higher than normal). Most affected individuals, however, do not exhibit the classic clinical phenotype....

Changes that occur at the level of the plasma membrane see

It is accepted that some of the most important changes accompanying the capacitation process are at the level of the sperm plasma membrane. Capacitation-associated alterations in the sperm plasma membrane architecture can be rapid Gadella and Figure 6.2 Current models for lateral membrane polarity dynamics upon sperm capacitation. A Formation of lipid ordered microdomains in the membrane lipid rafts that exclude freely diffusable transmembrane proteins and attracts GPI-anchored peripheral...

Sperm DNA damage assays and human fertility

Many assays for sperm chromatin structure have been developed in an attempt to determine whether cases of idiopathic male infertility could be explained by the sperm DNA being damaged. The rationale is that DNA damage may not be reflected in the sperm morphology, motility, or even its ability to fertilize the oocyte. However, damaged sperm DNA would be expected to prevent or reduce the spermatozoon's potential to fertilize and or inhibit embryo development. Several excellent reviews have...