Role of RGMc as a Neogenin Ligand in Follicular Development in the Ovary.
Yu Jin KimYoungJoon ParkYeo Reum ParkYoung Sang KimHye Ran LeeSang Jin LeeMyung Joo KimKyuBum KwackJung Jae KoJae-Ho LeePublished in: Biomedicines (2021)
There is currently no cure for infertility in women with a poor ovarian response (POR). Neogenin is reported to be abundantly expressed in the ovary; however, its role in mammalian follicular development is unclear and its ligand and signaling pathway remain uncertain. We systematically investigated the role of neogenin and the ligand repulsive guidance molecule c (RGMc) during follicular development. We treated hyperstimulated mouse ovaries with RGMc and analyzed follicular development. Furthermore, we investigated clusters of up/downregulated genes in RGMc-treated ovaries using whole-transcriptome next-generation sequencing (NGS). In addition, we investigated whether expression of up/downregulated factors identified by NGS was also altered in cumulus cells (CCs) of patients with a POR. The number of oocytes was 40% higher in RGMc-treated ovaries than in control ovaries. NGS data indicated that prostaglandin D2 (PGD2) was involved in the RGMc signaling pathway during follicular development. RGMc treatment significantly elevated the PGD2 level in culture medium of CCs obtained from patients with a POR. Our results demonstrate that RGMc as neogenin ligand promotes follicular development in ovaries via the PGD2 signaling pathway. Therefore, it may be possible to use RGMc for ovarian stimulation in patients with a POR.
Keyphrases
- signaling pathway
- induced apoptosis
- gene expression
- poor prognosis
- epithelial mesenchymal transition
- metabolic syndrome
- type diabetes
- genome wide
- adipose tissue
- newly diagnosed
- big data
- atomic force microscopy
- transcription factor
- deep learning
- high resolution
- artificial intelligence
- skeletal muscle
- rna seq
- insulin resistance
- bioinformatics analysis