Targeted Metabolomics Study: The Association Between Ovarian Function and Amino Acid Level Changes in Breast Cancer Patients Before and After Chemotherapy.

Cyclophosphamide (CTX) is a primary medicine for curing breast cancer which often caused premature ovarian insufficiency (POI). Our recent publication reveals that CTX induced POI by promoting the expression of SLC1A4, a transporter of serine efflux, in ovarian granulosa cells (GCs). Here, we report that there is a closed connection between the reduction of serum serine and ovarian hypofunction in the breast cancer patients treated with CTX or women of childbearing age who are suffered from the staying-up-late. Additionally, we observe that dietary serine supplementation protects mice from CTX-induced POI without altering its anti-breast cancer. Furthermore, we demonstrate that the elevated serine promoted S1P synthesis, and in turn, inhibit the nuclear translocation of Nrf2 and consequent HO-1 expression, to suppress ferroptosis in GCs. Our study reveal that the chemotherapy-induced or idiopathic POI shared the same mechanisms, indicating that serine is a critical factor for maintaining ovarian function.