Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway
Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopaus...
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2020-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2020/9725898 |
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| author | Fangui Zhao Wenjun Wang |
| author_facet | Fangui Zhao Wenjun Wang |
| author_sort | Fangui Zhao |
| collection | DOAJ |
| description | Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation. |
| format | Article |
| id | doaj-art-edee29757ce646a396ed4039ad496a1f |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-edee29757ce646a396ed4039ad496a1f2025-02-03T05:52:26ZengWileyInternational Journal of Endocrinology1687-83371687-83452020-01-01202010.1155/2020/97258989725898Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT PathwayFangui Zhao0Wenjun Wang1Department of Ultrasound Diagnosis, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, ChinaDiminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.http://dx.doi.org/10.1155/2020/9725898 |
| spellingShingle | Fangui Zhao Wenjun Wang Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway International Journal of Endocrinology |
| title | Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway |
| title_full | Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway |
| title_fullStr | Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway |
| title_full_unstemmed | Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway |
| title_short | Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway |
| title_sort | gengnianchun recipe protects ovarian reserve of rats treated by 4 vinylcyclohexene diepoxide via the akt pathway |
| url | http://dx.doi.org/10.1155/2020/9725898 |
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