Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice
Abstract Background Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cell...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-024-01388-2 |
| _version_ | 1797247100905324544 |
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| author | Shih-Yun Chen Tse-En Wang Wei-Yun Lee Ya-Yi Yang Hong-Chun Lai Fuko Matsuda Haruhiko Kosek You-Tzung Chen Sheng-Hsiang Li Pei-Shiue Tsai |
| author_facet | Shih-Yun Chen Tse-En Wang Wei-Yun Lee Ya-Yi Yang Hong-Chun Lai Fuko Matsuda Haruhiko Kosek You-Tzung Chen Sheng-Hsiang Li Pei-Shiue Tsai |
| author_sort | Shih-Yun Chen |
| collection | DOAJ |
| description | Abstract Background Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. Results We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. Conclusion Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice. |
| first_indexed | 2024-04-24T19:53:20Z |
| format | Article |
| id | doaj.art-e97a3d438afd49a59d8b4328358b2c73 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-24T19:53:20Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-e97a3d438afd49a59d8b4328358b2c732024-03-24T12:29:14ZengBMCJournal of Ovarian Research1757-22152024-03-0117111310.1186/s13048-024-01388-2Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in miceShih-Yun Chen0Tse-En Wang1Wei-Yun Lee2Ya-Yi Yang3Hong-Chun Lai4Fuko Matsuda5Haruhiko Kosek6You-Tzung Chen7Sheng-Hsiang Li8Pei-Shiue Tsai9Department of Veterinary Medicine, National Taiwan UniversityGraduate Institute of Veterinary Medicine, National Taiwan UniversityGraduate Institute of Veterinary Medicine, National Taiwan UniversityGraduate Institute of Veterinary Medicine, National Taiwan UniversityDepartment of Veterinary Medicine, National Taiwan UniversityDepartment of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of TokyoCenter for Integrative Medical Sciences (IMS), RIEKNResearch Center for Developmental Biology and Regenerative Medicine, National Taiwan UniversityDepartment of Medical Research, MacKay Memorial HospitalDepartment of Veterinary Medicine, National Taiwan UniversityAbstract Background Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. Results We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. Conclusion Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.https://doi.org/10.1186/s13048-024-01388-2Oocyte developmentQSOX2EstrogenGranulosa cellsFemale reproduction |
| spellingShingle | Shih-Yun Chen Tse-En Wang Wei-Yun Lee Ya-Yi Yang Hong-Chun Lai Fuko Matsuda Haruhiko Kosek You-Tzung Chen Sheng-Hsiang Li Pei-Shiue Tsai Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice Journal of Ovarian Research Oocyte development QSOX2 Estrogen Granulosa cells Female reproduction |
| title | Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice |
| title_full | Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice |
| title_fullStr | Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice |
| title_full_unstemmed | Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice |
| title_short | Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice |
| title_sort | cre loxp and tamoxifen induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice |
| topic | Oocyte development QSOX2 Estrogen Granulosa cells Female reproduction |
| url | https://doi.org/10.1186/s13048-024-01388-2 |
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