The role of calcium in capacitation-evoked changes in mammalian sperm metabolism

Adjusting to new metabolic conditions is a general task many cell types have to master. At the molecular level, the underlying metabolic pathway adaptations and regulatory signaling mechanisms are not well understood. While sperm stored in the cauda epididymis require very little energy, they suddenly have to increase their energy production during ejaculation to support motility and capacitation. This proposal aims to investigate how sperm activate and regulate changes in central carbon metabolic pathway activity to adjust for the increased energy demand, building on capacitating sperm exhibiting enhanced glycolysis and oxidative phosphorylation activity. KO mouse models revealed that Ca2+-dependent signaling mediated via CatSper is essential for capacitation and hyperactivation. CatSper might also be involved in regulating sperm metabolic reprogramming since sperm intracellular ATP levels and capacitation-induced increase in mitochondrial Ca2+ levels are dependent on the complex. Using a combination of mass spectrometry, stable isotope labeling, and genetic and pharmacological approaches to block intracellular Ca2+ changes, this proposal aims to investigate the crosstalk between sperm metabolic reprogramming during capacitation and CatSper-mediated Ca2+ signaling. This will advance the understanding of the molecular mechanisms underlying sperm capacitation, with potential implications for addressing male infertility and developing non-hormonal contraceptives. Project Number: 1R01HD117669-01A1 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Melanie Balbach | Institution: MICHIGAN STATE UNIVERSITY, EAST LANSING, MI | Award Amount: $501,659 | Activity Code: R01 | Study Section: Cellular, Molecular and Integrative Reproduction Study Section[CMIR] View on NIH RePORTER: https://reporter.nih.gov/project-details/11297097