Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis.

Autor:	Prokai D; Division of Reproductive Endocrinology and Infertility, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Pudasaini A; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; GenomeDesigns Laboratory, LLC, 314 Stonebridge Drive, Richardson, TX 75080, USA., Kanchwala M; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Moehlman AT; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Waits AE; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Chapman KM; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Chaudhary J; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Acevedo J; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Cecil H. & Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Keller P; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Cecil H. & Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Chao X; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Carr BR; Division of Reproductive Endocrinology and Infertility, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Hamra FK; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; Cecil H. & Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2020 Dec 01; Vol. 24 (1), pp. 101880. Date of Electronic Publication: 2020 Dec 01 (Print Publication: 2021).
DOI:	10.1016/j.isci.2020.101880
Abstrakt:	In adult males, spermatogonia maintain lifelong spermatozoa production for oocyte fertilization. To understand spermatogonial metabolism we compared gene profiles in rat spermatogonia to publicly available mouse, monkey, and human spermatogonial gene profiles. Interestingly, rat spermatogonia expressed metabolic control factors Foxa1 , Foxa2 , and Foxa3. Germline Foxa2 was enriched in Gfra1 Hi and Gfra1 Low undifferentiated A-single spermatogonia. Foxa2-bound loci in spermatogonial chromatin were overrepresented by conserved stemness genes ( Dusp6, Gfra1, Etv5, Rest, Nanos2, Foxp1 ) that intersect bioinformatically with conserved glutathione/pentose phosphate metabolism genes ( Tkt, Gss, Gc l c , Gc l m, Gpx1, Gpx4, Fth ), marking elevated spermatogonial GSH:GSSG. Cystine-uptake and intracellular conversion to cysteine typically couple glutathione biosynthesis to pentose phosphate metabolism. Rat spermatogonia, curiously, displayed poor germline stem cell viability in cystine-containing media, and, like primate spermatogonia, exhibited reduced transsulfuration pathway markers. Exogenous cysteine, cysteine-like mercaptans, somatic testis cells, and ferroptosis inhibitors counteracted the cysteine-starvation-induced spermatogonial death and stimulated spermatogonial growth factor activity in vitro . Competing Interests: A.P. is an employee of GenomeDesigns Laboratory, LLC., and F.K.H. is a founder and consultant of GenomeDesigns Laboratory, LLC and a member of its scientific advisory board. A provisional patent application has been filled on portions of this work (Inventor: F.K.H.). D.P., M.K., A.T.M., A.E.W., K.M.C., J.C., J.A., P.K., X.C., and B.R.C. declare no competing interests. (© 2020 The Author(s).)
Databáze:	MEDLINE
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