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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.

ABSTRACT:

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.

INSTRUMENT(S): Diode array detection MS - alternating - reverse-phase

PROVIDER: MTBLS13561 | MetaboLights | 2025-12-23

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13561_LC-DAD_alternating_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13561_LC-DAD_alternating_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13561.txt	Txt

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Serine inhibits granulosa cell ferroptosis to maintain ovarian function

Project description: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.

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