[Frontiers in Bioscience 16, 1344-1363, January 1, 2011]

Markers of human sperm functions in the ICSI era

Monica Muratori, Sara Marchiani, Lara Tamburrino, Gianni Forti, Michaela Luconi, Elisabetta Baldi

Department of Clinical Physiopathology, Andrology and Endocrinology Units, Center of Excellence "DeNothe", University of Florence, Italy


Figure 1. Schematic representation of the main steps of the fertilization process. Sperm capacitation and development of hyperactivated motility occur both at various levels of the female genital tract and are needed both to cross the oocyte cumulus and zona pellucida. Physiological acrosome reaction occurs following the contact with the zona. In the boxes, the possible molecular markers for each step are indicated.

Figure 2..Schematic representation of the main intracellular signalling pathways that are activated during the process of capacitation and development of hyperactivated motility. Early events during the process of capacitation include cholesterol removal from the membrane, a process which is stimulated by an extracellular cholesterol acceptor (physiologically albumin) and inhibited by glycodelins, entry of calcium (Ca2+) and bicarbonate (HCO3-). Another early event is represented by intracellular alkalinization (regulated by membrane potential extracellular pH and zinc), which is involved both in calcium and tyrosine phosphorylation increase occurring later. HCO3- leads to activation of Sacy and the cAMP/PKA pathway. Autocrine production of reactive oxygen species (ROS), nitric oxide (NO) and PAF has been demonstrated during capacitation. All these pathways converge in an increase of tyrosine phosphorylation of proteins. The increase of intracellular Ca2+ limits the increase of tyrosine phosphorylation by a poorly defined mechanism that may involve PTP. ras-MEK/MAPK and PKC activation and serine/threonine phosphorylation of proteins have been shown to occur during capacitation but their role in the process remains to be clearly defined.Pathways involved in development of sperm hyperactivated motility, include entry of Ca2+ through CatSper calcium channels whose role in motility has been recently disclosed in a KO mouse model, and autocrine synthesis of PAF which exert a positive effect. Hyperactivated motility is stimulated by inhibitors of PI3K through increase AKAP tyrosine phosphorylation and AKAP-PKA interaction. CatSper can be also activated by intracellular alkalinization due to the outward transport of protons through Hv1 Voltage-Gated channel.Dotted arrows indicate inhibiting pathways. Interrogation marks indicate lack of definitive proofs of the involvement of a given pathway in the process. Abbreviations: SACY, soluble adenylate cyclase; AKAPs, A-kinase-anchoring proteins; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; NO, nitric oxide; PAF, platelet-activating factor; PDE, Phosphodiesterase; PKA, protein kinase A; PKC, protein kinase C; PI3K, phosphatydil inositol 3 kinase; PTK, protein tyrosine kinase; PTP protein tyrosine phosphatase; Src, cellular homologue of transforming gene of Rous sarcoma virus; reactive oxygen species (ROS).