Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis
Summary: 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 spermatogon...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220310774 |
| _version_ | 1819059657781542912 |
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| author | David Prokai Ashutosh Pudasaini Mohammed Kanchwala Andrew T. Moehlman Alexandrea E. Waits Karen M. Chapman Jaideep Chaudhary Jesus Acevedo Patrick Keller Xing Chao Bruce R. Carr F. Kent Hamra |
| author_facet | David Prokai Ashutosh Pudasaini Mohammed Kanchwala Andrew T. Moehlman Alexandrea E. Waits Karen M. Chapman Jaideep Chaudhary Jesus Acevedo Patrick Keller Xing Chao Bruce R. Carr F. Kent Hamra |
| author_sort | David Prokai |
| collection | DOAJ |
| description | Summary: 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 Gfra1Hi and Gfra1Low 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, Gclc, Gclm, 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. |
| first_indexed | 2024-12-21T14:14:35Z |
| format | Article |
| id | doaj.art-7a851f768b5b49019ec1a24e649bc647 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-21T14:14:35Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-7a851f768b5b49019ec1a24e649bc6472022-12-21T19:00:57ZengElsevieriScience2589-00422021-01-01241101880Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine BiosynthesisDavid Prokai0Ashutosh Pudasaini1Mohammed Kanchwala2Andrew T. Moehlman3Alexandrea E. Waits4Karen M. Chapman5Jaideep Chaudhary6Jesus Acevedo7Patrick Keller8Xing Chao9Bruce R. Carr10F. Kent Hamra11Division of Reproductive Endocrinology and Infertility, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; GenomeDesigns Laboratory, LLC, 314 Stonebridge Drive, Richardson, TX 75080, USAMcDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment 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, USADepartment 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, USAMcDermott 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, USADivision 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, USADepartment 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; Corresponding authorSummary: 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 Gfra1Hi and Gfra1Low 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, Gclc, Gclm, 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.http://www.sciencedirect.com/science/article/pii/S2589004220310774Biological SciencesDevelopmental BiologySystems Biology |
| spellingShingle | David Prokai Ashutosh Pudasaini Mohammed Kanchwala Andrew T. Moehlman Alexandrea E. Waits Karen M. Chapman Jaideep Chaudhary Jesus Acevedo Patrick Keller Xing Chao Bruce R. Carr F. Kent Hamra Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis iScience Biological Sciences Developmental Biology Systems Biology |
| title | Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis |
| title_full | Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis |
| title_fullStr | Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis |
| title_full_unstemmed | Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis |
| title_short | Spermatogonial Gene Networks Selectively Couple to Glutathione and Pentose Phosphate Metabolism but Not Cysteine Biosynthesis |
| title_sort | spermatogonial gene networks selectively couple to glutathione and pentose phosphate metabolism but not cysteine biosynthesis |
| topic | Biological Sciences Developmental Biology Systems Biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220310774 |
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