Sperm Ca2+ Signaling and Energy Pathways in basic science and ART

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Project Summary Abstract Infertility and subfertility are critical health problems affecting about 9 % of couples worldwide. Since the first successful “Test-Tube” baby in 1978, over 5 million babies were born using Assisted Reproductive Technology (ART). ART includes such techniques as in vitro fertilization (IVF), intrauterine insemination (IUI), intracytoplasmic sperm injection (ICSI) and embryo transfer techniques. ART is used in humans, and in animals of economic relevance. In humans alone, IVF and ICSI are used ~ 800,000 times per year. In all species, the limiting factor for successful pregnancies to occur is obtaining good quality preimplantation embryos which have a direct influence in implantation and pregnancy rates. Capacitation involves crosstalk between metabolic and signaling pathways. We showed that a short incubation with the Ca2+ ionophore A23187[7] can induce in vitro fertilizing capacity in sperm from sterile knock-out (KO) genetic models. We hypothesized that, at least, in part, A23187’s effects were due to changes in metabolism. When sperm metabolism was changed using starvation and rescue protocols, we observed that intracellular Ca2+ was elevated. This proposal has basic and applied goals. The basic science objective is to understand the molecular basis of these methods with particular emphasis on the crosstalk between calcium and metabolic pathways. At the translational level, our goal is to use novel sperm incubation conditions to improve ART. This administrative supplement to support Dr. William David Weber’s career development has new approaches and it is synergic to the parent grant HD38082. The application also focuses in a mentoring plan as well as in enhancing Dr. Weber’s research skills to become an independent researcher.