Transcriptome analysis reveals that cyclophosphamide induces premature ovarian failure by blocking cholesterol biosynthesis pathway

Publication date: Available online 23 October 2019Source: Life SciencesAuthor(s): Qi Li, Xinglan An, Xiaxia Man, Meiran Chu, Tianchuang Zhao, Hao Yu, Ziyi LiAbstractAimsThe present study aimed to investigate the effects of cyclophosphamide (Cytoxan, CTX) on premature ovarian failure (POF) in mice and its regulatory mechanisms by transcriptome analysis.Main methodsFemale C57BL/6 mice were treated with a single intraperitoneal injection of 70 mg/kg CTX. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were measured by enzyme-linked immunosorbent assay (ELISA), and follicular structure differences were observed by hematoxylin and eosin (H&E) staining. The main mechanism of POF was investigated by RNA-seq data, protein-protein interaction (PPI) networks and qPCR analysis.Key findingsThe serum levels of estradiol (E2) were significantly decreased and those of follicle-stimulating hormone (FSH) were significantly increased compared to the control group. The ovarian weights of the mice in the CTX group were reduced, and abnormal follicular structures were also observed in the CTX group. The RNA-seq data show that the downregulated genes were related to the cholesterol biosynthesis pathway. The protein-protein interaction (PPI) network and qPCR analyses further confirm that the PPAR signaling pathway and the ovarian infertility genes were also involved in blocking the cholesterol biosynthesis pathway. The differences were statistically significant.SignificanceOur...
Source: Life Sciences - Category: Biology Source Type: research