About 10 percent of American families are affected by infertilily. Among which, one-third 01 these cases are due to female factOfs, one third to male factOfs, and the remainder are a mixture or have unknown causes. Mitochondrial dysfunction is responsible fOf a wide variety of severe mitochondrial diseases. Impairment of mitoc:hondrial function is one of the factors thaI contribute to infertility. In addition, it is associa ted with a series of other human diseases and conditions, including atherosclerosis and cardiovascular disease. insulin resistance, age-related neurodegenerative diseases, human ageing, and infertjljty. Mammalian models with defined mitochondrial dysfunction suitable fOf reproductive disease studies are nOI available at present. We recently generated a mouse mutant, Jmmp2l""""""""T~JD7P
Aim 1 is to determine the damages caused by elevated superoxide generation on germ cells of older mutant males.
Aim 2 is 10 study tile effects of mitochondrial dysfunction on germ cell apoptosis. Together, experiments proposed in this application will answer questions such as how elevated mitochondrial superoxide generation can damage male germ cells, impair spermatogenesis, and trigger germ cell apoptosis. Data obtained from this project wiU improve our understanding of the effects of mitochondrial dysfunction on male reproductive and benefit the developing of new treatments for male infertilily.
About 10 percent of American families are affected by infertility. Among which, one-third of these cases are due to female factors, one third to male factors, and the remainder are a mixture or have unknown causes. Impairment of mitochondrial function is one of the factors that contribute to infertility. In this proposal, we will use a novel mouse model to study the effects of mitochondrial dysfunction in human reproduction. This work will improve our understanding of the effects of mitochondrial dysfunction on male reproductive systems, enable us to better understand the mechanism of human infertility, and develop novel treatments.
| Bharadwaj, Manish S; Zhou, Yu; Molina, Anthony J et al. (2014) Examination of bioenergetic function in the inner mitochondrial membrane peptidase 2-like (Immp2l) mutant mice. Redox Biol 2:1008-15 |
| Han, Changjie; Zhao, Qingguo; Lu, Baisong (2013) The role of nitric oxide signaling in food intake; insights from the inner mitochondrial membrane peptidase 2 mutant mice. Redox Biol 1:498-507 |
| Jiao, Yan; Bishop, Colin E; Lu, Baisong (2012) Mex3c regulates insulin-like growth factor 1 (IGF1) expression and promotes postnatal growth. Mol Biol Cell 23:1404-13 |
| George, Sunil K; Jiao, Yan; Bishop, Colin E et al. (2012) Oxidative stress is involved in age-dependent spermatogenic damage of Immp2l mutant mice. Free Radic Biol Med 52:2223-33 |
| George, Sunil K; Jiao, Yan; Bishop, Colin E et al. (2011) Mitochondrial peptidase IMMP2L mutation causes early onset of age-associated disorders and impairs adult stem cell self-renewal. Aging Cell 10:584-94 |
