1. Progesterone affects clinic oocyte yields by coordinating with follicle stimulating hormone via PI3K/AKT and MAPK pathways
- Author
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Hui Long, Li Wang, Sha Yu, Weina Yu, Qiuju Chen, Lun Suo, Mingru Yin, Ling Wu, Yanping Kuang, Renfei Cai, and Qifeng Lyu
- Subjects
0301 basic medicine ,endocrine system ,Medicine (General) ,Science (General) ,medicine.drug_class ,media_common.quotation_subject ,medicine.medical_treatment ,Ovary ,Biology ,Andrology ,03 medical and health sciences ,Follicle-stimulating hormone ,Mice ,Phosphatidylinositol 3-Kinases ,Q1-390 ,0302 clinical medicine ,R5-920 ,medicine ,Animals ,Humans ,Ovulation ,Protein kinase B ,Progesterone ,media_common ,Multidisciplinary ,In vitro fertilisation ,Antral follicle ,Oocyte ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Ovary stimulation ,Oocytes ,Medicine ,Female ,Signal pathway ,Gonadotropin ,Follicle Stimulating Hormone ,Mitogen-Activated Protein Kinases ,Phosphatidylinositol 3-Kinase ,Proto-Oncogene Proteins c-akt ,Oocyte yield - Abstract
Graphical abstract The schematic diagram. Schematic illustration of the signaling cascades by which progesterone coordinates with FSH to regulate the proliferation of granular cells to slow down follicle growth during ovarian stimulation by PI3K/AKT and MAPK pathways., Highlights • Progesterone reduced oocyte yields in clinic. Yields were rescued by the higher dose of hMG. • Progesterone downregulated follicle growth and consequently reduced oocyte yields. • Progesterone inhibited granular cell proliferation via MAPK and PI3K/AKT pathways. • Progesterone and FSH coordinated follicle growth via signalling crosstalk in granular cells., Introduction As an effective inhibitor of premature ovulation, progestin was introduced to a novel ovarian stimulation regimen for infertility treatment. However, the local action of progestin on the ovary and its effect on clinical outcomes have not been described. Objectives The influence of progesterone administration on clinical oocyte outcomes and the mechanisms involved in the coordination of progesterone and follicle stimulating hormone (FSH) on follicle growth and oocyte yields were investigated. Methods Clinical outcomes of patients undergoing ovarian stimulation for in vitro fertilization were analyzed. The murine ovarian stimulation model and follicle culture system were used to evaluate the effects of progesterone on oocyte yield, follicle development, granular cell proliferation, and hormone secretion. Phospho-specific protein microarrays were used to explore involved signaling pathways. Results Progesterone decreased clinical oocyte yields, and yields were rescued with an increased dose of human menopausal gonadotropin. Administration of progesterone inhibited murine granular cell proliferation and reduced the growth rate of follicles; both of which were rescued by FSH. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) were identified as pivotal signaling pathways to integrate progesterone into the FSH signaling network in granular cells. Conclusion Progesterone inhibited granular cell proliferation and antral follicle growth during ovarian stimulation, and subsequently influenced oocyte outcomes in the clinical setting. Progesterone coordinated with FSH to regulate follicle growth through PI3K/AKT and MAPK signaling pathways. These findings advance our knowledge regarding the ovarian response to gonadotropins during progestin-primed ovarian stimulation and create an opportunity to manipulate individual oocyte yields.
- Published
- 2021