**1. Introduction**

Standard examination of human semen currently remains a main test for male fertility disorders. The concentration (total sperm count) and motility of spermatozoa and the content of morphologically normal (typical) spermatozoa are thought to reflect the fertilization potential of the semen [1]. Although their values in fertile men are generally higher than in sterile ones, there is a substantial overlap between the two populations, indicating that other important factors affect fertility, but are not assessed in conventional assay [2]. In this regard, methods to assess the functional properties of spermatozoa and thus to evaluate their reproductive (fertilizing) potential have intensely been developed in the past years.

Light microscopy, which is employed in a conventional sperm testing, reports the numbers of sperm heads and tails, their sizes and relative arrangement, the presence and sizes of the

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acrosome and nuclear vacuole, and sperm movement. An ultrastructural examination makes it possible to look inside the spermatozoon and to study what is inaccessible by light microscopy, including the extent of chromatin condensation and the structures of the perinuclear theca (PT), its postacrosomal segment, the centriole, the axoneme, and periaxonemal elements of the tail.

To achieve this unique extent of compaction, sperm DNA is packaged in a specific manner, which substantially differs from chromatin packaging in somatic cells. In somatic cells, DNA is packaged to produce the so-called nucleosomes. The DNA double helix is wrapped around

Ultrastructure of Spermatozoa from Infertility Patients http://dx.doi.org/10.5772/intechopen.71596 73

During sperm maturation, canonical histones are replaced by testis-specific histones and then by protamines, basic proteins with lower molecular weight and high concentration of argi-

As spermatozoa progress through the epididymis, disulfide bridges form between cysteine residues of protamines to further stabilize the DNA-protamine complex and morphologically determine condensation of the dense nucleoprotamine complex in the sperm nucleus [7]. Sperm chromatin is decondensed and acquires a nucleosomal structure after fertilization. The organization of sperm chromatin facilitates the transfer of compacted DNA into the oocyte and ensures its reverse transformation so that genetic information becomes readily available

Approximately 5–10% of genomic DNA remains free of protamines and preserves a nucleosomal structure in mature human spermatozoa (for a review, see [9]). The role of the residual nucleosomes remained unclear until recently and was explained in three studies, which were published simultaneously in 2010 [10–12]. Residual nucleosomes were found to mark the genes for early embryo development factors and to perform an important function in the epigenetic regulation of embryo development. A gene distribution between protamineassociated and histone-containing (nucleosomal) regions of chromatin follows a certain pattern. Residual nucleosomes occur in the promoters of early developmental genes (e.g., *HOX*

Condensation associated with histone-to-protamine replacement metabolically inactivates chromatin and, on the other hand, contributes to its mechanical and chemical stability, thus protecting the paternal genome from nucleases while spermatozoa travel through the male and female reproductive tracts and interact with the oocyte. Residual nucleosomes mark early developmental genes. Normal chromatin condensation is indicative of the sperm potential to

Spermatozoa with incomplete chromatin condensation in the nucleus are almost always detectable in ejaculate samples from fertile donors. Granular and fibrillary structures of approximately 40 nm in diameter are seen in these cells. The chromatin structure observed in the spermatozoa is similar to that of elongated spermatids, and their chromatin is conse-

What is a possible role of distorted chromatin compaction? The disturbance of chromatin condensation is a consequence of a reduced protamine content [14]. Hammoud et al. [15] have recently found that defects in histone-to-protamine exchange lead to a random distribution of nucleosomal (histone-associated and potentially active) chromatin in infertile patients, in contrast to a programmed nucleosomal chromatin distribution in fertile men. Distorted

a specific complex of canonical histones (a histone octamer) [4].

nine and cysteine (for a review, see [5, 6]).

gene clusters), imprinted gene loci, and miRNA genes.

**2.2. Abnormal chromatin condensation in spermatozoa**

quently known as immature chromatin (**Figure 1c**, **d**) [13].

produce a normally developing embryo.

in the developing embryo [8].

Every function of the spermatozoon is now possible to attribute to a particular morphological structure owing to the achievements of modern molecular biology, cytology, and genetics. The morphology of spermatozoa reflects how competent they are to fertilize (enter) the oocyte and to provide for embryo development.
