Spermatozoa centrosome mediated head-tail coupling

The National Institute of Child Health and Human Development awarded the University of Toledo $448,793 on September 1, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to investigate spermatozoa head-kinking mechanics and their role in male fertility.

The research addresses molecular and cellular mechanisms underlying human spermatozoa navigation and egg fertilization. The project will employ rabbits as a genetic model and high-resolution microscopy to test the hypothesis that the spermatozoon centrosome dynamically connects the head and tail for efficient fertilization. Specific aims include investigating the relationship between head-kinking and tail-beating across a wide parameter range, determining the role of the POC1B protein and head-kinking in spermatozoa fertilization, and identifying abnormal head-kinking patterns in infertile men. The work represents a paternal mechanism pathway for understanding infertility.

Performance occurs at Ottawa Hills, Ohio, with the period of performance running from September 1, 2026, through May 31, 2031. This is a Project Grant, the standard assistance type for NIH research project awards.

Abstract

The role of human spermatozoa is to navigate to the EGG and fertilize IT; however, the molecular and cellular mechanisms that underlie this critical function, essential for fertility, are not well understood. The avidor-reiss lab recently proposed that the spermatozoa neck and the atypical centrioles within IT mediate a novel movement, which they named spermatozoa head-kinking. They also hypothesize that the force for this kinking originates from the tail, and the centrioles act as a transmission system, converting the up-and-down sliding movement within the tail into lateral head-kinking. These studies were based on bovine spermatozoa snap-frozen during swimming. Still, the precise manner in which the human spermatozoa centrioles function during live spermatozoa swimming remains unresolved. Several factors contribute to this lack of understanding due to technical challenges. This research proposes to overcome these challenges by employing rabbits as a genetic model, carefully selecting genetic manipulations and experimental conditions, and utilizing high-resolution microscopy techniques. The long-term goal is to understand the role of the spermatozoon neck in fertilization. The current objective is to provide the first mechanistic understanding of spermatozoa head-kinking and to provide clinical evidence that IT is critical for fertilization. The central hypothesis is that the spermatozoon centrosome dynamically connects the head and tail for efficient fertilization. We will test this hypothesis by pursuing three specific aims: (1) to investigate the relationship between head-kinking and tail-beating in rabbits in a wide parameter range, (2) to determine the role of POC1B and head-kinking in spermatozoa fertilization, and (3) to identify abnormal head-kinking in infertile men. This project innovatively tests a paternal mechanism for infertility. For this purpose, the project utilizes state-of- the-art methods to assess spermatozoa centrosome function, developed by the avidor-reiss lab. This research is original because IT is the first to investigate a paradigm-shifting hypothesis regarding the role of the spermatozoon's centrosome in sperm motility and penetration of the EGG's protective layers. Furthermore, due to the challenges of establishing causality in humans stemming from ethical concerns and the limitations of using mice, which lack spermatozoa centrioles, this study provides a critical foundation for exploring the central hypothesis by studying a relevant model animal (rabbit) as well as performing correlative studies in human spermatozoa. This research aims to enhance the understanding of infertility and the role of spermatozoa centrioles. Ultimately, the knowledge gained from these studies will inform research, diagnostics, and treatments for infertility.