Work

Serine inhibits granulosa cell ferroptosis to maintain ovarian function

Year: 2026

Type: article

Abstract: Cyclophosphamide (CTX) is a primary medicine for curing breast cancer which often causes premature ovarian insufficiency (POI). Our recent publication reveals that CTX induces 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 promotes S1P synthesis, and in turn, inhibits the nuclear translocation of Nrf2 and consequent HO-1 expression, to suppress ferroptosis in GCs. Our study reveals that the chemotherapy-induced or idiopathic POI share the same mechanisms, indicating that serine is a critical factor for maintaining ovarian function. This study demonstrates that the reduced serum serine in patients with chemotherapy or women with poor sleep, is linked to the decline of ovarian function. Serine supplementation prevented ovarian damage in mice by inhibiting ferroptosis in ovarian granulosa cells, without affecting chemotherapy efficacy.

Source: Nature Communications

DOI: 10.1038/s41467-026-68440-1