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Yanyan Gao, Xiufeng Bai, Dejiu Zhang, Chunsheng Han, Jing Yuan, Wenbin Liu, Xintao Cao, Zilei Chen, Fugen Shangguan, Zhenyuan Zhu, Fei Gao, Yan Qin
Elongation factor 4 (EF4) is a key quality-control factor in translation. Despite its high conservation throughout evolution, EF4 deletion in various organisms has not yielded a distinct phenotype. Here we report that genetic ablation of mitochondrial EF4 (mtEF4) in mice causes testis-specific dysfunction in oxidative phosphorylation, leading to male infertility. Deletion of mtEF4 accelerated mitochondrial translation at the cost of producing unstable proteins. Somatic tissues overcame this defect by activating mechanistic (mammalian) target of rapamycin (mTOR), thereby increasing rates of cytoplasmic translation to match rates of mitochondrial translation...
May 2016: Nature Structural & Molecular Biology
Leanne S Whitmore, Ping Ye
Metabolic pathways are increasingly postulated to be vital in programming cell fate, including stemness, differentiation, proliferation, and apoptosis. The commitment to meiosis is a critical fate decision for mammalian germ cells, and requires a metabolic derivative of vitamin A, retinoic acid (RA). Recent evidence showed that a pulse of RA is generated in the testis of male mice thereby triggering meiotic commitment. However, enzymes and reactions that regulate this RA pulse have yet to be identified. We developed a mouse germ cell-specific metabolic network with a curated vitamin A pathway...
2015: PloS One
Sara Correia, Henrique J Cardoso, José E Cavaco, Sílvia Socorro
In the mammalian testis, spermatogenesis is a highly coordinated process of germ cell development, which ends with the release of 'mature' spermatozoa. The fine regulation of spermatogenesis is strictly dependent on sex steroid hormones, which orchestrate the cellular and molecular events underlying normal development of germ cells. Sex steroids actions also rely on the control of germ cell survival, and the programmed cell death by apoptosis has been indicated as a critical process in regulating the size and quality of the germ line...
2015: Expert Reviews in Molecular Medicine
Chen Zhang, Ji Wu
No abstract text is available yet for this article.
May 2015: Biology of Reproduction
Nicole O McPherson, Julie A Owens, Tod Fullston, Michelle Lane
Obesity and type 2 diabetes are increasingly prevalent across all demographics. Paternal obesity in humans and rodents can program obesity and impair insulin sensitivity in female offspring. It remains to be determined whether these perturbed offspring phenotypes can be improved through targeted lifestyle interventions in the obese father. Using a mouse model, we demonstrate that diet or exercise interventions for 8 wk (2 rounds of spermatogenesis) in obese founder males restores insulin sensitivity and normalized adiposity in female offspring...
May 1, 2015: American Journal of Physiology. Endocrinology and Metabolism
Zahida Parveen, Zohra Bibi, Nousheen Bibi, Juergen Neesen, Sajid Rashid
Programmed cell death or apoptosis plays a vital physiological role in the development and homeostasis. Any discrepancy in apoptosis may trigger testicular and neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. Tcte3 (T-complex testis expressed 3) is an accessory component of axonemal and cytoplasmic dynein which expresses predominantly in meiotic and postmeiotic germ cells. It plays an essential role during spermatogenesis; however, to explore its diverse and complex functioning in male germ cell apoptosis, requires further prosecution...
October 24, 2014: Computational Biology and Chemistry
Teng Zhang, Mark W Murphy, Micah D Gearhart, Vivian J Bardwell, David Zarkower
In mammals, a key transition in spermatogenesis is the exit from spermatogonial differentiation and mitotic proliferation and the entry into spermatocyte differentiation and meiosis. Although several genes that regulate this transition have been identified, how it is controlled and coordinated remains poorly understood. Here, we examine the role in male gametogenesis of the Doublesex-related gene Dmrt6 (Dmrtb1) in mice and find that Dmrt6 plays a crucial role in directing germ cells through the mitotic-to-meiotic germ cell transition...
October 2014: Development
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