Transcriptomics-based Exploration of the Effects of Oviductus Ranae on Rats with Impaired Follicular Development

Objective: The effects of Oviductus Ranae (OR) on cyclophosphamide-induced follicular developmental disorders were analyzed from the perspective of transcriptomics, which provided sufficient theoretical and experimental basis for the study of estrogen-like mechanism of OR. Methods: Sixty screened female Wistar rats were randomly divided into control group (C), model group (M), positive group (P), OR low-dose (ORL) and high-dose group (ORH). Except for the control group, all rats were injected with cyclophosphamide intraperitoneally to establish the rat model of follicular development dysfunction. Except for the model group, the other rats were given corresponding drugs by gavage, and the serum sex hormone contents were determined after 14~16 days of continuous gavage. The ovaries and uterus were extracted and weighed for recording and calculating the organ index. One ovary and uterus were stained with HE staining to calculate the number of follicles at all levels and the thickness of the endometrium, while the other ovary was analyzed by transcriptome, and the differentially expressed genes were screened and analyzed by GO and KEGG enrichment analyses. Results: The results showed that the rat follicular development dysfunction model was successfully established. Compared with the rats in the M, the wet weight and index of the uterus of rats in the ORL and ORH significantly increased (P<0.05), and the contents of P and E₂ significantly increased (P<0.05). The number of preantral follicles and corpus luteum of rats in the ORL and ORH increased significantly (P<0.05), and the thickness of endometrium increased significantly (P<0.01), with statistically significant differences, and the number of antral follicles in the ORL increased significantly (P<0.05). The transcriptome results showed that there were 738 and 572 differential genes between the ORL, ORH and M, respectively. GO enrichment analysis enriched 1790 and 1616 entries and the KEGG enrichment analysis was mainly focused on the PI3K/Akt signaling pathway and the B-cell receptor signaling pathway. Conclusion: OR can effectively improve serum sex hormone levels, ovarian follicular development, and endometrial atrophy in rats with cyclophosphamide-induced follicular dysfunction, and its molecular mechanism may be related to pathways and genes such as PI3K/Akt and B-cell receptor.