1354-1374 Gopal_S_Gupta 365

INTRODUCTION Spermatozoa are highly specialized for delivering the male genome to the egg. Approximately 15–20% of human couples are affected by infertility and about half of these cases of infertility can be attributed to men. In men, the main causes of infertility are oligozoospermia (low sperm production), asthenozoospermia (poor sperm motility), teratozoospermia (abnormal sperm morphology) and azoospermia (lack of sperm production), which account for 20–25% of the infertility cases. Efficient motility is crucial for reproductive success. Sperm capacitation and sperm activation are prerequisite steps before sperm-egg interaction and ovum fertilization. Sperm hyperactivity can be observed if glycolysis is not hampered. Hyperactivity of sperm is important to generate mechanical thrust for its penetration in zona pellucida surrounding the egg. Hyperactivity is apparently induced in the female genital tract when spermatozoa undergo complex metabolic and structural changes that are collectively termed capacitation [Eddy 2007]. How glycolysis, hyperactivity, and sperm fertility are functionally linked is not clear. In other words, we do not know how glycolysis in spermatozoa is organized and regulated. The prime function of sperm metabolism is to provide the flagellar motor with free energy by hydrolysis of ATP, which seems to come mainly through glycolytic pathway (Fig. 1). Fig.1. Glycolytic pathway starting with glucose to pyruvate and associated pathways: Human spermatozoa rely mainly on glycolysis as the source of ATP fueling the energy-demanding processes of motility and capacitation. Human spermatozoa utilize exogenous pyruvate to enhance glycolytic ATP production and, events that are crucial for male fertility. The glycolysis is dependent on exogenous pyruvate, which indirectly feeds the accelerated glycolysis with NAD through the LDH-mediated conversion of pyruvate to lactate. In addition, oxidative phosphorylation does contribute some ATP for human sperm motility but not enough to sustain high motility (Nascimento et al., 2008; Hereng et al., 2011) Abstract: Efficient sperm motility is crucial for reproductive success. Sperm capacitation and sperm activation are prerequisites for sperm-egg interaction and ovum fertilization. Hyperactivity of sperm can be observed if glycolysis is not hampered. How glycolysis, hyperactivity, and sperm fertility are functionally linked is not clear. Glycolysis is the major source of ATP required for sperm flagellar movement, capacitation, and fertilization. The unique isozymic pattern of glycolytic enzymes bound to sperm flagella with specific kinetics seems as a controlling mechanism for requisite energy output of the glycolysis. Furthermore, mammalian sperm contain also atypical isozymes of phosphoglucose isomerase, triosephosphate isomerase, phosphoglycerate mutase, enolase and others. The molecular bases for the testis-specific expression are diverse. For instance PGK-2 is encoded by different gene, while some originate from alternative promoters or by alternative splicing. An unusual feature of GAPDHS is a novel proline-rich N-terminal 105-amino acid sequence not present in other isozymes, whereas ALDOA_V2 and ALDOART1 have a novel 54-55-amino acid sequence at N-terminal region. While LDH-C and PGK-2 lack N-terminal features, Hexokinase, HK1S has an unusual N-terminal spermatogenic cell-specific sequence. This review describes the up-todate, extended knowledge on isozymic pattern and characteristics of enzymes of pathway of glycolysis in sperm with a view to understand the mechanism of sperm motility and their future potential as targets for contraception by chemical and/or immunological methods.