Research Paper Volume 12, Issue 17 pp 16951—16962

Esculentoside A rescues granulosa cell apoptosis and folliculogenesis in mice with premature ovarian failure

Zhenteng Liu1, *, , Fenghua Li1, *, , Jingwen Xue1, *, , Meimei Wang1, , Shoucui Lai1, , Hongchu Bao1, , Shunzhi He1, ,

  • 1 Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai 264000, Shandong, People's Republic of China
* Equal contribution

Received: May 2, 2020       Accepted: June 12, 2020       Published: August 5, 2020
How to Cite

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Follicular atresia is one of the main processes for the loss of granulosa cells and oocytes from the mammalian ovary and any impairment to premature ovarian failure. Large numbers of studies have demonstrated that granulosa cell apoptosis causes follicular atresia, yet the rescue of these cells remains elusive. We aimed to use Esculentoside A (3-O-b-D-glucopyranosyl-1, 4-b-D-xylopyranosyl) phytolaccagenin, a saponin extracted from Phytolacca esculenta roots, as a potential rescue agent for the apoptosis of granulosa cells. Our results revealed the rescue of normal body and ovary weights, normal ovarian histo-architecture of ovaries, and hormones levels with regular estrus cycle. Consistently, the expression of proliferating and anti-apoptotic markers, i.e. KI67 and BCL-2 in granulosa cells, was enhanced. Meanwhile, the expressions of pro-apoptotic markers, which were BAX and CASPASEs (CASPASE-9 and CASPASE-3), were prominently reduced in Esculentoside A-induced premature ovarian failure mice. Additionally, PPARγ, a potential therapeutic target, has also rescued its expression by treating the premature ovarian failure mice with Esculentoside A. Our results advocated that Esculentoside A could restore folliculogenesis in premature ovarian failure mice. Furthermore, it has the potential to be investigated as a therapeutic agent for premature ovarian failure.


POF: Premature ovarian failure; GCs: Granulosa cells; ROS: Reactive oxygen species; FSH: Follicle stimulating hormone; EA: Esculentoside A; TNF: Tumor necrosis factor; IL: Interleukin; LPS: Lipopolysaccharide; ELISA: Enzyme-linked immunosorbent assay.