Synthetic Egg:Sperm Fusion Assay (SEFA): A Diagnostic Test for Male Fertility

Abstract: SNYTHETIC EGG:SPERM FUSION ASSAY: A DIAGNOSTIC TEST FOR MALE FERTILITY The establishment of PS-Fertility, C-Corp was motivated by: 1) our recent findings from the laboratory that phosphatidylserine (PS) on the surface of viable sperm is necessary for sperm:egg fusion; 2) that sperm can fuse with myoblast cells in a PS-dependent manner; and 3) the inability of conventional semen analysis assays to provide meaningful information about sperm function. Our overall goal of this SBIR is to refine our simple rapid synthetic egg:sperm fusion assay and further develop our business model. The fusion assay will serve as a surrogate assay for sperm:egg fusion, to quantify the fusogenic fertilization-competent sperm in an ejaculate. Clinicians view semen analysis as a perfunctory assay, rather than an insightful test to acquire information toward improved assisted reproductive technique strategies. Our market research, performed as part of the NSF I-Corps program, revealed that, overwhelmingly, clinicians would welcome a diagnostic tool that could provide new information about male infertility, specifically sperm health/function. The premise for this application stems our preliminary studies, where we find an unexpected exposure of the lipid phosphatidylserine (PS), which is normally associated with apoptotic cells, on the surface of viable and motile sperm. Further, PS recognition receptors are expressed on the oocytes, and blocking/loss of some of these receptors impairs fertilization. In this Phase 1 SBIR application, we will further develop our synthetic egg:sperm fusion assay (SEFA) that will test the fusion (fertilization) competency of sperm cells. To our knowledge, there are no semen analysis tests that provide information about the potential ability of a sperm to fertilize an egg. In Aim 1 we will demonstrate the feasibility of better quantifying male infertility though a new fertility kit and in Aim 2 we will perform a pilot study to evaluate the use of the new kit with a larger cohort of real-world samples. Development of this male fertility test `SEFA' will provide fertility experts and thus patients with information about male fertility that is currently not available from any other diagnostic. This information will aid in personalizing fertility treatments and reducing emotional and economic costs.