Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries
Ovarian aging hampers in vitro fertilization in assisted reproductive medicine and has no cure. Lipoprotein metabolism is associated with ovarian aging. It remains unclear how to overcome poor follicular development with aging. Upregulation of the low-density lipoprotein receptor (LDLR) enhances oog...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/8/7263 |
| _version_ | 1797605059062661120 |
|---|---|
| author | Yu Jin Kim Yong Il Cho JuYi Jang Yun Dong Koo Sung Woon Park Jae Ho Lee |
| author_facet | Yu Jin Kim Yong Il Cho JuYi Jang Yun Dong Koo Sung Woon Park Jae Ho Lee |
| author_sort | Yu Jin Kim |
| collection | DOAJ |
| description | Ovarian aging hampers in vitro fertilization in assisted reproductive medicine and has no cure. Lipoprotein metabolism is associated with ovarian aging. It remains unclear how to overcome poor follicular development with aging. Upregulation of the low-density lipoprotein receptor (LDLR) enhances oogenesis and follicular development in mouse ovaries. This study investigated whether upregulation of LDLR expression using lovastatin enhances ovarian activity in mice. We performed superovulation using a hormone and used lovastatin to upregulate LDLR. We histologically analyzed the functional activity of lovastatin-treated ovaries and investigated gene and protein expression of follicular development markers, using RT-qPCR and Western blotting. Histological analysis showed that lovastatin significantly increased the numbers of antral follicles and ovulated oocytes per ovary. The in vitro maturation rate was 10% higher for lovastatin-treated ovaries than for control ovaries. Relative LDLR expression was 40% higher in lovastatin-treated ovaries than in control ovaries. Lovastatin significantly increased steroidogenesis in ovaries and promoted the expression of follicular development marker genes such as anti-Mullerian hormone, Oct3/4, Nanog, and Sox2. In conclusion, lovastatin enhanced ovarian activity throughout follicular development. Therefore, we suggest that upregulation of LDLR may help to improve follicular development in clinical settings. Modulation of lipoprotein metabolism can be used with assisted reproductive technologies to overcome ovarian aging. |
| first_indexed | 2024-03-11T04:55:48Z |
| format | Article |
| id | doaj.art-1a6fdcaa154948d396846a5b84a5fcfa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:55:48Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1a6fdcaa154948d396846a5b84a5fcfa2023-11-17T19:37:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248726310.3390/ijms24087263Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse OvariesYu Jin Kim0Yong Il Cho1JuYi Jang2Yun Dong Koo3Sung Woon Park4Jae Ho Lee5CHA Fertility Center Seoul Station, Seoul 04637, Republic of KoreaWonju Severance Christian Hospital, Wonju 22070, Republic of KoreaDepartment of Biomedical Sciences, CHA University, Pocheon 11160, Republic of KoreaDepartment of Biomedical Sciences, CHA University, Pocheon 11160, Republic of KoreaCHA Fertility Center Seoul Station, Seoul 04637, Republic of KoreaCHA Fertility Center Seoul Station, Seoul 04637, Republic of KoreaOvarian aging hampers in vitro fertilization in assisted reproductive medicine and has no cure. Lipoprotein metabolism is associated with ovarian aging. It remains unclear how to overcome poor follicular development with aging. Upregulation of the low-density lipoprotein receptor (LDLR) enhances oogenesis and follicular development in mouse ovaries. This study investigated whether upregulation of LDLR expression using lovastatin enhances ovarian activity in mice. We performed superovulation using a hormone and used lovastatin to upregulate LDLR. We histologically analyzed the functional activity of lovastatin-treated ovaries and investigated gene and protein expression of follicular development markers, using RT-qPCR and Western blotting. Histological analysis showed that lovastatin significantly increased the numbers of antral follicles and ovulated oocytes per ovary. The in vitro maturation rate was 10% higher for lovastatin-treated ovaries than for control ovaries. Relative LDLR expression was 40% higher in lovastatin-treated ovaries than in control ovaries. Lovastatin significantly increased steroidogenesis in ovaries and promoted the expression of follicular development marker genes such as anti-Mullerian hormone, Oct3/4, Nanog, and Sox2. In conclusion, lovastatin enhanced ovarian activity throughout follicular development. Therefore, we suggest that upregulation of LDLR may help to improve follicular development in clinical settings. Modulation of lipoprotein metabolism can be used with assisted reproductive technologies to overcome ovarian aging.https://www.mdpi.com/1422-0067/24/8/7263LDLRlovastatinfollicular developmentoocytesin vitro maturation |
| spellingShingle | Yu Jin Kim Yong Il Cho JuYi Jang Yun Dong Koo Sung Woon Park Jae Ho Lee Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries International Journal of Molecular Sciences LDLR lovastatin follicular development oocytes in vitro maturation |
| title | Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries |
| title_full | Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries |
| title_fullStr | Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries |
| title_full_unstemmed | Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries |
| title_short | Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries |
| title_sort | lovastatin an up regulator of low density lipoprotein receptor enhances follicular development in mouse ovaries |
| topic | LDLR lovastatin follicular development oocytes in vitro maturation |
| url | https://www.mdpi.com/1422-0067/24/8/7263 |
| work_keys_str_mv | AT yujinkim lovastatinanupregulatoroflowdensitylipoproteinreceptorenhancesfolliculardevelopmentinmouseovaries AT yongilcho lovastatinanupregulatoroflowdensitylipoproteinreceptorenhancesfolliculardevelopmentinmouseovaries AT juyijang lovastatinanupregulatoroflowdensitylipoproteinreceptorenhancesfolliculardevelopmentinmouseovaries AT yundongkoo lovastatinanupregulatoroflowdensitylipoproteinreceptorenhancesfolliculardevelopmentinmouseovaries AT sungwoonpark lovastatinanupregulatoroflowdensitylipoproteinreceptorenhancesfolliculardevelopmentinmouseovaries AT jaeholee lovastatinanupregulatoroflowdensitylipoproteinreceptorenhancesfolliculardevelopmentinmouseovaries |