Ceramide: a pivotal lipid mediator shaping female reproductive homeostasis and pathophysiology

Ceramide, a central hub in sphingolipid metabolism, serves as a critical bioactive signalling mediator that integrates lipid metabolism with multiple signalling pathways, primarily promoting autophagy and apoptosis. It influences female reproductive homeostasis and pathophysiology through multiple dimensions: altered ceramide levels have been observed in various reproductive disorders—such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) and endometriosis (EM)—as well as across the female lifespan. These changes impact key processes including gonadotropin release, follicular development, and uterine microenvironment homeostasis. This review systematically summarizes the effects of ceramide on female fertility, highlighting its role as a pivotal entry point for understanding reproductive endocrine disorders in women. Modulating ceramide levels may represent a promising therapeutic strategy to enhance fertility and promote female reproductive health. Similar content being viewed by others Abbreviations - ACTH: - Adrenocorticotropic hormone - AD: - Alzheimer’s disease - aSMase: - Acid sphingomyelinase - Akt: - Protein kinase B - AMPK: - AMP-activated protein kinase - ASAH1: - Acid ceramidase - ATF4: - Activating transcription factor 4 - CDase: - Ceramidase - Cer: - Ceramide - CerS: - Ceramide synthase - CERT: - Ceramide transfer protein - CL: - Corpus luteum - CMH: - Glycosphingolipid monoglycosylceramide - CNL: - Ceramide nanoliposome - COX-2: - Cyclooxygenase-2 - CPP: - Chronic pelvic pain - Cyt c: - Mitochondrial cytochrome c - DDIT3: - DNA damage-inducible transcript 3 - Des: - Dihydroceramide desaturase - DEGS1: - Δ4-desaturase - E2: - Oestradiol - EAI: - Endometriosis-associated infertility - EC: - Endometrial Cancer - EM: - Endometriosis - ER: - Endoplasmic reticulum - ERK: - Extracellular signal-regulated kinase - FASD: - Foetal alcohol spectrum disorder - FA: - Fatty acid - FOXO3: - Forkhead box O3 - FSH: - Follicle-stimulating hormone - Gb3Cer: - Trihexosylceramide - GDM: - Gestational diabetes mellitus - GlcCer: - Glucosylceramide - GLUT4: - Glucose transporter 4 - GlyCers: - Glycosylceramide - GnRH: - Gonadotropin-releasing hormone - GPCR: - G protein-coupled receptor - HbA1c: - Hemoglobin A1c - HCG: - Human chorionic gonadotropin - HDL: - High-density lipoprotein - HexCer: - Hexosylceramide - HI: - Hyperinsulinaemia - HA: - Hyperandrogenaemia - HPG: - Hypothalamic‒pituitary‒gonadal - HPO: - Hypothalamic‒pituitary‒ovarian - hs-CRP: - High-sensitivity C-reactive protein - IL-1β: - Interleukin-1β - IR: - Insulin resistance - KLF15: - Kruppel-like factor 15 - KRG: - Korean red ginseng - LacCer: - Lactosylceramide - LDL-C: - Low-density lipoprotein cholesterol - LH: - Luteinizing hormone - LRG1: - Leucine-rich α-2-glycoprotein 1 - MAM: - Mitochondria or mitochondria-associated membrane - MOMP: - Mitochondrial outer membrane permeabilization - MPF: - Maturation-promoting factor - mPR: - Membrane progesterone receptor - mTOR: - Mechanistic target of rapamycin - nSMase: - Neutral sphingomyelinase - Nrf2: - Nuclear factor erythroid 2-related factor 2 - OC: - Ovarian cancer - OS: - Oxidative stress - P4: - Progesterone - PABC: - Pregnancy-associated breast cancer - PC: - Phosphatidylcholine - PE: - Preeclampsia - PFOS: - Perfluorooctanesulfonic acid - PGE2: - Prostaglandin E2 - PH: - Pleckstrin homology domain - PI3K: - Phosphoinositide 3-kinase - PIP2: - Phosphatidylinositol 4:5-bisphosphate - PIP3: - Phosphatidylinositol 3:4:5-trisphosphate - PKCζ: - Protein kinase C-ζ - PLC: - Phospholipase C - POI: - Premature ovarian insufficiency - PP: - Precocious puberty - PP2A: - Protein phosphatase 2 A - PPARα: - Peroxisome proliferator-activated receptorα - PPARγ: - Proliferation-activated receptor gamma - PPP: - Peripheral precocious puberty - PTEN: - Phosphatase and tensin homolog - RPL: - Recurrent pregnancy loss - ROS: - Reactive oxygen species - RTK: - Receptor tyrosine kinase - RYGB: - Roux-en-Y gastric bypass - S1P: - Sphingosine-1-phosphate - S1PR: - Sphingosine-1-Phosphate Receptor - SGPL1: - Sphingosine-1-phosphate lyase 1 - SHBG: - Sex hormone-binding globulin - SM: - Sphingomyelin - SMase: - Sphingomyelinase - SphK: - Sphingosine kinase - SPT: - Serine palmitoyltransferase - T: - Testosterone - TCGA: - The Cancer Genome Atlas - T1D: - Type 1 diabetes - T2DM: - Type 2 diabetes mellitus - TLR: - Toll-like receptor - TMA: - Trimethylamine - TNF-α: - Tumour necrosis factor-α - TNFR: - Tumor necrosis factor receptor - TRAF2: - Tumour necrosis factor receptor-associated factor 2 - TRIB3: - Tribbles homologue 3 - UPR: - Unfolded protein response

None. Funding This work was supported by the Beijing Research Ward Excellence Program (BRWEP2024W0940901004), the Beijing Natural Science Foundation (7242162), the National Key Research of Development Program of China (2024YFC2707300), the National Natural Science Foundation of China (82288102, 32541060,82571886), the Key Clinical Projects of Peking University Third Hospital (BYSY2022045), and the Joint Research Project of the Shijiazhuang-Peking University Cooperation Program. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Wang, W., Zhang, F., Huang, L. et al. Ceramide: a pivotal lipid mediator shaping female reproductive homeostasis and pathophysiology. J Ovarian Res (2026). https://doi.org/10.1186/s13048-026-02169-9 Received: Accepted: Published: DOI: https://doi.org/10.1186/s13048-026-02169-9