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

ABSTRACT: 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, PPAR?, 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.

SUBMITTER: Liu Z

PROVIDER: S-EPMC7521512 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Liu Zhenteng Z Li Fenghua F Xue Jingwen J Wang Meimei M Lai Shoucui S Bao Hongchu H He Shunzhi S

Aging 20200805 17

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 <i>Phytolacca esculenta</i> roots, as a potential rescue agent fo ...[more]

PMID: 32759462

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Project description:Premature ovarian failure (POF) is the pathological aging of ovarian tissue. We have previously established a cyclophosphamide-induced mouse POF model and found that cyclophosphamide caused significant damage and apoptosis of mouse ovarian granulosa cells (mOGCs). To systematically explore the molecular biologic evidence of cyclophosphamide-induced mOGC damage at the gene transcription level, RNA-Seqwas used to analyse the differences in mOGC transcriptomes between POF and control (PBS) mice. The sequencing results showed that there were 18765 differential transcription genes between the two groups, of which 192 were significantly up-regulated (log2 [POF/PBS] > 2.0) and 116 were significantly down-regulated (log2 [POF/PBS] < -4.0). Kyoto Encyclopedia of Genes and Genomes analysis found that the neuroactive ligand-receptor interaction pathway was significantly up-regulated and metabolic pathways were significantly down-regulated in the POF group. Gene Ontology analysis showed that the expression of plasma membrane, regulation of transcription and ion binding functions were significantly up-regulated in the POF group, while the expression of cell and cell parts, catalytic activity and single-organism process functions were significantly down-regulated. Finally, protein interaction analysis reveals that in the ovarian steroidogenesis pathway, three Cytochrome P450 family proteins-Cyp1a1, Cyp11a1 and Cyp2u1-interact with Fdx1 to form an interactive network. These three proteins were down-regulated in POF cells, suggesting that they are likely direct regulatory targets of cyclophosphamide. RNA-Seq high-throughput screening analysis demonstrated that cyclophosphamide damage to mOGCs was achieved through its impacts on multiple pathways and on the transcription activities of multiple target genes. Among them, the protein network consisting of the cytochrome P450 family Fdx1, Cyp17a1, Cyp11a1 and Cyp2u1 is a potential new biomarker of mOGC damage in POF in mice.

Dataset Information

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

Publications

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

Similar Datasets

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