Loss of IDH3b causes male infertility with normal vision

Rachel McNeel*, Siyan Zhu, Jianhai Du, Ph.D.
West Virginia University Eye Institute, West Virginia University, Morgantown, WV 26505

Presentation Category: Science & Technology (Oral Presentation)

Student’s Major: Chemistry

Isocitrate dehydrogenase 3 (IDH3) is responsible for catalyzing the irreversible conversion of isocitrate into alpha-ketoglutarate and CO2 in the mitochondrial Krebs cycle. IDH3 is comprised of beta (IDH3B) subunits and alpha (IDH3A) subunits, which are essential for assembly and cooperative function. Mutations of IDH3b are reported to be associated with recessive retinitis pigmentosa, the neurodegeneration of rods and cones in the retina that eventually results in blindness. We found that the deletion of the IDH3b gene in mice had normal visual function and retinal morphology. Unexpectedly, the male IDH3b knockout mice were infertile. Results from sperm counts and immunohistology showed that there were almost no elongated spermatozoa in the epididymis from the IDH3b knockout mice. Furthermore, IDH3b knockout mice had disorganized flagellum in their sperm. Metabolite analysis data showed that the substrates and upstream intermediates including isocitrate were accumulated more than 10-folds in the testes of the IDH3b knockout mice. In conclusion, IDH3b gene is dispensable for vision but essential for sperm development.

Funding: WVUMedicine, BrightFocus Foundation, NIH, Retina Research Foundation

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course