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Serine inhibits granulosa cell ferroptosis to maintain ovarian function

ABSTRACT: Cyclophosphamide (CTX) is a primary medicine for curing breast cancer which often caused premature ovarian insufficiency (POI). Our recent publication revealed that CTX induced POI by promoting the expression of SLC1A4, a transporter of serine efflux, in ovarian granulosa cells (GCs). Here, we reported that there was 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 were suffered from the staying-up-late. Additionally, we observed that dietary serine supplementation protected mice from CTX-induced POI without altering its anti-breast cancer. Furthermore, we demonstrated that the elevated serine promoted S1P synthesis, and in turn, inhibited the nuclear translocation of Nrf2 and consequent HO-1 expression, to suppress ferroptosis in GCs. Our study revealed that the chemotherapy-induced or idiopathic POI shared the same mechanisms, indicating that serine was a critical factor for maintaining ovarian function.

ORGANISM(S): Mus musculus

PROVIDER: GSE314714 | GEO | 2025/12/23

REPOSITORIES: GEO

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

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2025-12-23 | MTBLS13561 | MetaboLights

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