MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1
Abstract Background Preimplantation embryonic lethality is a driver of female infertility. Certain microRNAs (miRNAs) have previously been demonstrated to play important roles in the regulation of embryogenesis. Methods Normally developing blastocysts and arrested embryos were collected from patient...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
|
| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12958-022-01044-8 |
| _version_ | 1811198528799637504 |
|---|---|
| author | Ou Jian Ni MengXia Xing Shiyu Meng QingXia Zou QinYan Ding Jie Wang Wei Wan Jiaojiao Li Hong Huang Yining |
| author_facet | Ou Jian Ni MengXia Xing Shiyu Meng QingXia Zou QinYan Ding Jie Wang Wei Wan Jiaojiao Li Hong Huang Yining |
| author_sort | Ou Jian |
| collection | DOAJ |
| description | Abstract Background Preimplantation embryonic lethality is a driver of female infertility. Certain microRNAs (miRNAs) have previously been demonstrated to play important roles in the regulation of embryogenesis. Methods Normally developing blastocysts and arrested embryos were collected from patients undergoing intracytoplasmic sperm injection (ICSI), and the expression of specific miRNAs therein was evaluated by qPCR. The overexpression of target molecule miR-145 in early mice embryos was achieved via oocyte microinjection, enabling the subsequent monitoring of how such overexpression impacted embryonic development. Bioinformatics approaches were utilized to identify putative miR-145 target mRNAs, and luciferase reporter assessments were implemented to confirm the ability of miR-145 to regulate Abca1 in HEK293T cells. The functional relationship between miR-145 and Abca1 in the mice’s embryonic development was then confirmed through rescue assays. Results Abnormally increased miR-145 expression was observed in patients’ arrested embryos, and the exogenous overexpression of this miRNA significantly suppressed mural blastocyst formation. Mechanistically, miR-145 was found to bind to the 3′-untranslated area of the Abca1 mRNA in HK293T cells, thus suppressing its expression and increasing embryonic cholesterol levels. In line with the importance of these cholesterol levels to embryogenesis, the upregulation of Abca1 was sufficient to rescue the observed change in cholesterol levels and the associated retardation of mice embryonic development that occurred in response to the overexpression of miR-145. Conclusion The regulatory dynamics of the miR-145/Abca1 axis play an important role in shaping normal embryonic development. |
| first_indexed | 2024-04-12T01:31:51Z |
| format | Article |
| id | doaj.art-75f9912cd0014ac689abec1b0391939d |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-04-12T01:31:51Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-75f9912cd0014ac689abec1b0391939d2022-12-22T03:53:27ZengBMCReproductive Biology and Endocrinology1477-78272022-12-0120111010.1186/s12958-022-01044-8MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1Ou Jian0Ni MengXia1Xing Shiyu2Meng QingXia3Zou QinYan4Ding Jie5Wang Wei6Wan Jiaojiao7Li Hong8Huang Yining9Center for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalCenter for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalCenter for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalCenter for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalCenter for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalCenter for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalCenter for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalPeking Jabrehoo Med-Tech Co., LtdCenter for Reproduction and Genetics, Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalPeking Jabrehoo Med-Tech Co., LtdAbstract Background Preimplantation embryonic lethality is a driver of female infertility. Certain microRNAs (miRNAs) have previously been demonstrated to play important roles in the regulation of embryogenesis. Methods Normally developing blastocysts and arrested embryos were collected from patients undergoing intracytoplasmic sperm injection (ICSI), and the expression of specific miRNAs therein was evaluated by qPCR. The overexpression of target molecule miR-145 in early mice embryos was achieved via oocyte microinjection, enabling the subsequent monitoring of how such overexpression impacted embryonic development. Bioinformatics approaches were utilized to identify putative miR-145 target mRNAs, and luciferase reporter assessments were implemented to confirm the ability of miR-145 to regulate Abca1 in HEK293T cells. The functional relationship between miR-145 and Abca1 in the mice’s embryonic development was then confirmed through rescue assays. Results Abnormally increased miR-145 expression was observed in patients’ arrested embryos, and the exogenous overexpression of this miRNA significantly suppressed mural blastocyst formation. Mechanistically, miR-145 was found to bind to the 3′-untranslated area of the Abca1 mRNA in HK293T cells, thus suppressing its expression and increasing embryonic cholesterol levels. In line with the importance of these cholesterol levels to embryogenesis, the upregulation of Abca1 was sufficient to rescue the observed change in cholesterol levels and the associated retardation of mice embryonic development that occurred in response to the overexpression of miR-145. Conclusion The regulatory dynamics of the miR-145/Abca1 axis play an important role in shaping normal embryonic development.https://doi.org/10.1186/s12958-022-01044-8Preimplantation embryonic lethalityICSImiR-145Abca1Cholesterol |
| spellingShingle | Ou Jian Ni MengXia Xing Shiyu Meng QingXia Zou QinYan Ding Jie Wang Wei Wan Jiaojiao Li Hong Huang Yining MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 Reproductive Biology and Endocrinology Preimplantation embryonic lethality ICSI miR-145 Abca1 Cholesterol |
| title | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
| title_full | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
| title_fullStr | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
| title_full_unstemmed | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
| title_short | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
| title_sort | mir 145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting abca1 |
| topic | Preimplantation embryonic lethality ICSI miR-145 Abca1 Cholesterol |
| url | https://doi.org/10.1186/s12958-022-01044-8 |
| work_keys_str_mv | AT oujian mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT nimengxia mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT xingshiyu mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT mengqingxia mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT zouqinyan mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT dingjie mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT wangwei mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT wanjiaojiao mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT lihong mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 AT huangyining mir145isupregulatedintheretardedpreimplantationembryosandmodulatescholesterollevelsinmicepreimplantationembryosthroughtargetingabca1 |