What is the structure and function of a sperm cell in relation to fertility?

Sperm Anatomy and Function in Relation to Fertility

Basic Structural Components

The human spermatozoon consists of three primary anatomical regions: the head containing the haploid nucleus and acrosome, the midpiece housing mitochondria for energy production, and the flagellum (tail) responsible for propulsion—each structure playing essential roles in achieving fertilization. 1, 2

Head Structure

• Contains highly condensed haploid DNA within the nucleus, surrounded by a thin cytoplasmic layer 3
• The acrosome caps the anterior portion of the head like a secretory granule, containing hydrolytic enzymes that facilitate penetration of the egg's outer layers during fertilization 3
• Structural abnormalities in head morphology are among the most frequently observed defects in infertile men, with the WHO lower reference limit for normal morphology being 4.0% 4, 3

Midpiece Architecture

• Houses the mitochondrial sheath arranged in a helical pattern around the axoneme, generating ATP to power flagellar movement 3, 2
• Connects the head to the tail via the neck region, which serves as the structural junction between these compartments 2, 5
• Energy metabolism in this region is critical for sustained sperm motility throughout the journey to the egg 3

Flagellar (Tail) Structure

• The tail represents the most complex sperm structure, involving over 1,000 proteins and containing the characteristic 9+2 microtubule arrangement of the axoneme surrounded by peri-axonemal structures 1
• The axoneme consists of nine outer doublet microtubules (DMTs) surrounding two central singlet microtubules, extending along the entire flagellar length 1, 6
• Outer dense fibers and the fibrous sheath provide additional structural support unique to mammalian sperm, distinguishing them from other ciliated cells 3, 6
• Recent cryo-electron microscopy studies have identified 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs), with 10 being sperm-specific 6

Functional Significance for Fertility

Motility Mechanisms

• Recent three-dimensional microscopy studies demonstrate that sperm move by spinning rather than simple swimming, with progressive motility requiring coordinated function of all flagellar components 1
• The WHO lower reference limit for progressive motility is 30% (29-31% CI), and for total motility (progressive plus non-progressive) is 42% (40-43% CI) 4
• Each flagellar subunit—axonemal and peri-axonemal structures—plays essential roles in motility, capacitation, hyperactivation, and ultimately fertilization 1

Capacitation and Fertilization

• Capacitation involves biochemical changes in the sperm membrane that prepare the cell for the acrosome reaction 3
• The acrosome reaction releases hydrolytic enzymes in a programmed manner to digest the zona pellucida and enable sperm-egg fusion 3
• Defects in capacitation or acrosome reaction processes significantly impact male fertility, even when sperm counts and motility appear normal 3

Genetic and Molecular Basis

Genetic Complexity

• Over 2,300 genes are involved in spermatogenesis, with mutations in flagellar development genes leading to motility defects and male infertility 1
• Approximately 6% of male infertility cases are related to genetic causes, and 4% of couples undergoing ICSI for male subfertility have chromosomal abnormalities 1
• Variants in 10 distinct MIPs have been associated with asthenozoospermia characterized by impaired motility without evident morphological abnormalities 6

Species and Tissue Specificity

• Human sperm DMTs lack some MIPs compared to mouse sperm DMTs, highlighting species-specific variations in flagellar structure 6
• Mammalian sperm exhibit considerable diversity, with overall lengths ranging from approximately 30 to 350 μm depending on species 5
• Despite this structural diversity, all sperm share the common functional goal of fertilizing the oocyte and activating embryonic development 5

Clinical Implications for Fertility Assessment

Diagnostic Parameters

• Assessment of multiple semen parameters (concentration, motility, morphology) provides better prediction of fertility success than any single parameter 7
• WHO lower reference limits include: semen volume 1.4 mL, sperm concentration 16 million/mL, total sperm number 39 million per ejaculate, and normal morphology 4.0% 4
• At least two semen analyses should be performed, ideally at least one month apart, due to significant intra-individual variability 4

Structural-Functional Correlations

• Proteins in sperm play vital roles in motility, capacitation, fertilization, egg activation, and embryo development, with molecular defects associated with low fertility or infertility 2
• The unique cellular architecture—with haploid DNA in minimal cytoplasm, mitochondria in the midpiece, and the tail enclosed by multiple membrane layers—reflects the specialized function of delivering genetic material to the oocyte 2
• Future diagnostic approaches may utilize sperm tail-associated genes, proteins, and subunits as markers of male fertility potential 1