Abstract
Premature ovarian insufficiency (POI) is a common female endocrine disease that is closely linked to ovarian function. Danggui Buxue Tang (DBT) is a classic prescription of traditional Chinese medicine that is helpful for rescuing ovarian function. However, the mechanism by which DBT rescues ovarian function remains unclear. This study explored the molecular mechanism of DBT with respect to apoptosis and related signals in ovarian cells. The quality control of DBT was performed by HPLC. After DBT intervention in the POI rat model, serum AMH/FSH/LH/E2 levels were detected by ELISA, follicles at various developmental stages were observed by HE staining, apoptosis was detected by TUNEL, and the expression profiles of Bcl-2 family proteins and key proteins in the Jak2/Foxo3a signaling pathway were evaluated by western blot. The results demonstrated that DBT could encourage the development of primary/secondary/antral follicles and increase the secretion of AMH. Moreover, DBT might inhibit Foxo3a by upregulating Jak2, thereby mediating Bcl-2 family activities and inhibiting apoptosis in ovarian cells. In conclusion, DBT promotes follicular development and rescues ovarian function by regulating Bcl-2 family proteins to inhibit cell apoptosis, which could be related to the Jak2/Foxo3a signaling pathway.
Highlights
Premature ovarian insufficiency (POI) refers to the occurrence of menopause before the age of 40, which can cause a series of diseases of the reproductive system, cardiovascular system, osteoporosis, and related conditions [1, 2]. e etiology of POI is not yet known
Our results showed that Danggui Buxue Tang (DBT) did not seem to have significant effects on FSH, E2, or LH levels, but compared with the model group, the decrease in AMH was recovered in the DBT group. is result implies that DBT has an effect on the restoration of AMH, which is the most important and sensitive response to ovarian function [34]
Consistent with a previous study [36], the western blot results in this study showed that apoptosis was clearly increased in the Vinylcyclohexene diepoxide (VCD) group, and our study showed that DBT could reverse this detrimental increase
Summary
Premature ovarian insufficiency (POI) refers to the occurrence of menopause before the age of 40, which can cause a series of diseases of the reproductive system, cardiovascular system, osteoporosis, and related conditions [1, 2]. e etiology of POI is not yet known. 70–80% of cases of POI have an unclear cause and are known as idiopathic premature ovarian insufficiency. One of the most notable characteristics of ovarian aging is the gradual loss of the primordial follicle pool [4], and metabolic products and oxidative stress have damaging effects on mitochondrial function and the development of oocytes. Granulosa cell apoptosis increases, which can aggravate follicle damage [5]. Ovarian granulosa cells surround the oocyte and provide hormones, regulatory factors, and signal factors for the development of follicles [6]. Abnormal apoptosis of oocytes or granulosa cells triggers follicle exhaustion, leading to ovarian aging [7]. Apoptosis plays an important role in vertebrates and is regulated by the interaction of three subgroups of Bcl-2 family proteins on the outer membrane of mitochondria: proapoptotic proteins, antiapoptotic proteins, and BH3-only proteins [13]. ese molecular signals influence each other in a complicated network, and the mechanism of POI has not yet been clarified
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