RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis
Abstract Background Retinoic acid (RA) plays important role in the maintenance and differentiation of the Müllerian ducts during the embryonic stage via RA receptors (RARs). However, the function and mechanism of RA-RAR signaling in the vaginal opening are unknown. Method We used the Rarα knockout m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12958-023-01084-8 |
| _version_ | 1797845687817207808 |
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| author | Nana Zheng Wenbo Zhang Xiaodan Zhang Biao Li Zhanying Wu Yashuang Weng Weiyong Wang Jingjing Miao Jing Yang Meijia Zhang Wei Xia |
| author_facet | Nana Zheng Wenbo Zhang Xiaodan Zhang Biao Li Zhanying Wu Yashuang Weng Weiyong Wang Jingjing Miao Jing Yang Meijia Zhang Wei Xia |
| author_sort | Nana Zheng |
| collection | DOAJ |
| description | Abstract Background Retinoic acid (RA) plays important role in the maintenance and differentiation of the Müllerian ducts during the embryonic stage via RA receptors (RARs). However, the function and mechanism of RA-RAR signaling in the vaginal opening are unknown. Method We used the Rarα knockout mouse model and the wild-type ovariectomized mouse models with subcutaneous injection of RA (2.5 mg/kg) or E2 (0.1 µg/kg) to study the role and mechanism of RA-RAR signaling on the vaginal opening. The effects of Rarα deletion on Ctnnb1 mRNA levels and cell apoptosis in the vaginas were analyzed by real-time PCR and immunofluorescence, respectively. The effects of RA on the expression of β-catenin and apoptosis in the vaginas were analyzed by real-time PCR and western blotting. The effects of E2 on RA signaling molecules were analyzed by real-time PCR and western blotting. Results RA signaling molecules were expressed in vaginal epithelial cells, and the mRNA and/or protein levels of RALDH2, RALDH3, RARα and RARγ reached a peak at the time of vaginal opening. The deletion of Rarα resulted in 25.0% of females infertility due to vaginal closure, in which the mRNA (Ctnnb1, Bak and Bax) and protein (Cleaved Caspase-3) levels were significantly decreased, and Bcl2 mRNA levels were significantly increased in the vaginas. The percentage of vaginal epithelium with TUNEL- and Cleaved Caspase-3-positive signals were also significantly decreased in Rarα −/− females with vaginal closure. Furthermore, RA supplementation of ovariectomized wild-type (WT) females significantly increased the expression of β-catenin, active β-catenin, BAK and BAX, and significantly decreased BCL2 expression in the vaginas. Thus, the deletion of Rarα prevents vaginal opening by reducing the vaginal β-catenin expression and epithelial cell apoptosis. The deletion of Rarα also resulted in significant decreases in serum estradiol (E2) and vagina Raldh2/3 mRNA levels. E2 supplementation of ovariectomized WT females significantly increased the expression of RA signaling molecules in the vaginas, suggesting that the up-regulation of RA signaling molecules in the vaginas is dependent on E2 stimulation. Conclusion Taken together, we propose that RA-RAR signaling in the vaginas promotes vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis. |
| first_indexed | 2024-04-09T17:44:10Z |
| format | Article |
| id | doaj.art-b0279bc0559544c5a042afced0f07dcb |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-04-09T17:44:10Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-b0279bc0559544c5a042afced0f07dcb2023-04-16T11:28:15ZengBMCReproductive Biology and Endocrinology1477-78272023-04-0121111110.1186/s12958-023-01084-8RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosisNana Zheng0Wenbo Zhang1Xiaodan Zhang2Biao Li3Zhanying Wu4Yashuang Weng5Weiyong Wang6Jingjing Miao7Jing Yang8Meijia Zhang9Wei Xia10Department of Reproductive Medicine Centre, Guangzhou First People’s Hospital, South China University of Technology Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyState Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural UniversityState Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural UniversityState Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyState Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural UniversitySchool of Basic Medical Sciences, Shanxi Medical University Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDepartment of Reproductive Medicine Centre, Guangzhou First People’s Hospital, South China University of TechnologyAbstract Background Retinoic acid (RA) plays important role in the maintenance and differentiation of the Müllerian ducts during the embryonic stage via RA receptors (RARs). However, the function and mechanism of RA-RAR signaling in the vaginal opening are unknown. Method We used the Rarα knockout mouse model and the wild-type ovariectomized mouse models with subcutaneous injection of RA (2.5 mg/kg) or E2 (0.1 µg/kg) to study the role and mechanism of RA-RAR signaling on the vaginal opening. The effects of Rarα deletion on Ctnnb1 mRNA levels and cell apoptosis in the vaginas were analyzed by real-time PCR and immunofluorescence, respectively. The effects of RA on the expression of β-catenin and apoptosis in the vaginas were analyzed by real-time PCR and western blotting. The effects of E2 on RA signaling molecules were analyzed by real-time PCR and western blotting. Results RA signaling molecules were expressed in vaginal epithelial cells, and the mRNA and/or protein levels of RALDH2, RALDH3, RARα and RARγ reached a peak at the time of vaginal opening. The deletion of Rarα resulted in 25.0% of females infertility due to vaginal closure, in which the mRNA (Ctnnb1, Bak and Bax) and protein (Cleaved Caspase-3) levels were significantly decreased, and Bcl2 mRNA levels were significantly increased in the vaginas. The percentage of vaginal epithelium with TUNEL- and Cleaved Caspase-3-positive signals were also significantly decreased in Rarα −/− females with vaginal closure. Furthermore, RA supplementation of ovariectomized wild-type (WT) females significantly increased the expression of β-catenin, active β-catenin, BAK and BAX, and significantly decreased BCL2 expression in the vaginas. Thus, the deletion of Rarα prevents vaginal opening by reducing the vaginal β-catenin expression and epithelial cell apoptosis. The deletion of Rarα also resulted in significant decreases in serum estradiol (E2) and vagina Raldh2/3 mRNA levels. E2 supplementation of ovariectomized WT females significantly increased the expression of RA signaling molecules in the vaginas, suggesting that the up-regulation of RA signaling molecules in the vaginas is dependent on E2 stimulation. Conclusion Taken together, we propose that RA-RAR signaling in the vaginas promotes vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis.https://doi.org/10.1186/s12958-023-01084-8Retinoic acid receptorVaginal openingApoptosisβ-cateninMouse |
| spellingShingle | Nana Zheng Wenbo Zhang Xiaodan Zhang Biao Li Zhanying Wu Yashuang Weng Weiyong Wang Jingjing Miao Jing Yang Meijia Zhang Wei Xia RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis Reproductive Biology and Endocrinology Retinoic acid receptor Vaginal opening Apoptosis β-catenin Mouse |
| title | RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis |
| title_full | RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis |
| title_fullStr | RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis |
| title_full_unstemmed | RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis |
| title_short | RA-RAR signaling promotes mouse vaginal opening through increasing β-catenin expression and vaginal epithelial cell apoptosis |
| title_sort | ra rar signaling promotes mouse vaginal opening through increasing β catenin expression and vaginal epithelial cell apoptosis |
| topic | Retinoic acid receptor Vaginal opening Apoptosis β-catenin Mouse |
| url | https://doi.org/10.1186/s12958-023-01084-8 |
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