The Role of Cathepsin L in Oocyte and Early Embryonic Development

doi:10.12280/gjszjk.20250442

Abstract

Abstract:

Cathepsin L (CTSL), a pivotal member of the lysosomal cysteine protease family, participates in the regulation of primordial follicle activation and ovulation by degrading extracellular matrix. The N-glycosylated CTSL variants emerge as key mediators driving oocyte quality deterioration by compromising mitochondrial function, amplifying oxidative stress, and disrupting spindle assembly. The aberrant expression of CTSL is intimately linked to reproductive aging. At the level of embryonic development, CTSL participates in fundamental biological events including maternal-to-zygotic transition, autophagy regulation and epigenetic reprogramming, suggesting that the dynamic activation of CTSL precisely directs early embryogenesis. The in-depth analysis of the roles of CTSL in the female reproductive regulatory network will enhance the understanding of the development mechanism of germ cells, which is expected to be applied in the clinical practice to improve the outcomes of assisted reproduction.

Key words: Cathepsin L, Oocytes, Embryonic development, Ovulation, Epigenesis, genetic

ZHU Qing, SONG Jia, TANG Huai-yun. The Role of Cathepsin L in Oocyte and Early Embryonic Development[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(1): 49-53.

References 31

[1]	Chi WY, Lee GH, Tang MJ, et al. Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation[J]. BMC Biol, 2024, 22(1):146. doi: 10.1186/s12915-024-01946-6.
[2]	Hu J, Wu J, Liu X, et al. Hypoxia enhances autophagy level of human sperms[J]. Sci Rep, 2024, 14(1):8465. doi: 10.1038/s41598-024-59213-1. pmid: 38605082
[3]	Li Z, Peluffo G, Stevens LE, et al. KDM4C inhibition blocks tumor growth in basal breast cancer by promoting cathepsin L-mediated histone H3 cleavage[J]. Nat Genet, 2025, 57(6):1463-1477. doi: 10.1038/s41588-025-02197-z.
[4]	Zhang J, Xia W, Zhou J, et al. Participation of preovulatory follicles in the activation of primordial follicles in mouse ovaries[J]. Int J Biol Sci, 2024, 20(10):3863-3880. doi: 10.7150/ijbs.95020. pmid: 39113716
[5]	Kondo Y, Rajapakse S, Ogiwara K. Involvement of cathepsin L in the degradation and degeneration of postovulatory follicle of the medaka ovary?[J]. Biol Reprod, 2023, 109(6):904-917. doi: 10.1093/biolre/ioad116. pmid: 37712895
[6]	Zhang K, Xu R, Zheng L, et al. Elevated N-glycosylated cathepsin L impairs oocyte function and contributes to oocyte senescence during reproductive aging[J]. Aging Cell, 2025, 24(2):e14397. doi: 10.1111/acel.14397.
[7]	Ezz MA, Takahashi M, Rivera RM, et al. Cathepsin L regulates oocyte meiosis and preimplantation embryo development[J]. Cell Prolif, 2024, 57(1):e13526. doi: 10.1111/cpr.13526.
[8]	Ibanez F, Vieira Rocha S, Dawson WO, et al. Gene silencing of cathepsins B and L using CTV-based, plant-mediated RNAi interferes with ovarial development in Asian citrus psyllid (ACP), Diaphorina citri[J]. Front Plant Sci, 2023, 14:1219319. doi: 10.3389/fpls.2023.1219319.
[9]	Raes A, Wydooghe E, Pavani KC, et al. Cathepsin-L Secreted by High-Quality Bovine Embryos Exerts an Embryotrophic Effect In Vitro[J]. Int J Mol Sci, 2023, 24(7):6563. doi: 10.3390/ijms24076563.
[10]	Dettleff P, Rodríguez J, Patiño-García D, et al. Molecular Characterization of Embryos with Different Buoyancy Levels in the Yellowtail Kingfish (Seriola lalandi)[J]. Animals(Basel), 2022, 12(6):720. doi: 10.3390/ani12060720.
[11]	Wang X, Liu D, Liu F, et al. Cathepsin L involved in the freezing resistance of murine normal hatching embryos and dormant embryos[J]. Reprod Biol, 2022, 22(1):100612. doi: 10.1016/j.repbio.2022.100612.
[12]	Jiang S, Xiong Y, Zhang W, et al. Molecular Characterization of a Novel Cathepsin L in Macrobrachium nipponense and Its Function in Ovary Maturation[J]. Front Endocrinol(Lausanne), 2021, 12:816813. doi: 10.3389/fendo.2021.816813.
[13]	Chen J, Guo P, Li Y, et al. Cathepsin L Contributes to Reproductive Diapause by Regulating Lipid Storage and Survival of Coccinella septempunctata (Linnaeus)[J]. Int J Mol Sci, 2022, 24(1):611. doi: 10.3390/ijms24010611.
[14]	Li C, Liu Z, Chen M, et al. Critical Role of Cathepsin L/V in Regulating Endothelial Cell Senescence[J]. Biology(Basel), 2022, 12(1):42. doi: 10.3390/biology12010042.
[15]	Peng Z, Luo XY, Li X, et al. Cathepsin L Promotes Pulmonary Hypertension via BMPR2/GSDME-Mediated Pyroptosis[J]. Hypertension, 2024, 81(12):2430-2443. doi: 10.1161/HYPERTENSIONAHA.124.22903. pmid: 39403807
[16]	Liu RD, Meng XY, Li CL, et al. Trichinella spiralis cathepsin L damages the tight junctions of intestinal epithelial cells and mediates larval invasion[J]. PLoS Negl Trop Dis, 2023, 17(12):e0011816. doi: 10.1371/journal.pntd.0011816.
[17]	Zhang Z, Wang J, Shi Y, et al. Cathepsin L promotes oesophageal squamous cell carcinoma development and may be associated with tumour-associated macrophages[J]. Heliyon, 2024, 10(7):e29273. doi: 10.1016/j.heliyon.2024.e29273.
[18]	Pei Z, Deng K, Xu C, et al. The molecular regulatory mechanisms of meiotic arrest and resumption in Oocyte development and maturation[J]. Reprod Biol Endocrinol, 2023, 21(1):90. doi: 10.1186/s12958-023-01143-0.
[19]	Li Y, Yang Y, Zhang Y, et al. Expression and cellular localization of insulin-like growth factor 3 in gonads of the seasonal breeding teleost silver pomfret (Pampus argenteus)[J]. Fish Physiol Biochem, 2022, 48(5):1377-1387. doi: 10.1007/s10695-022-01122-z. pmid: 36136164
[20]	Zhang JS, Li J, Meng JY, et al. The functional of cathepsin L in the ontogenesis and reproductive regulation of the Asian corn borer, Ostrinia furnacalis[J]. Sci Rep, 2025, 15(1):25214. doi: 10.1038/s41598-025-11318-x.
[21]	Robker RL, Russell DL, Espey LL, et al. Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases[J]. Proc Natl Acad Sci U S A, 2000, 97(9):4689-4694. doi: 10.1073/pnas.080073497.
[22]	Sriraman V, Richards JS. Cathepsin L gene expression and promoter activation in rodent granulosa cells[J]. Endocrinology, 2004, 145(2):582-591. doi: 10.1210/en.2003-0963. pmid: 14563703
[23]	Jin X, Wang K, Wang L, et al. RAB7 activity is required for the regulation of mitophagy in oocyte meiosis and oocyte quality control during ovarian aging[J]. Autophagy, 2022, 18(3):643-660. doi: 10.1080/15548627.2021.1946739.
[24]	Fu GX, Chen AF, Xu QM, et al. Cathepsin L deficiency results in reactive oxygen species (ROS) accumulation and vascular cells activation[J]. Free Radic Res, 2017, 51(11/12):932-942. doi: 10.1080/10715762.2017.1393665.
[25]	Harrath AH, Rahman MA, Bhajan SK, et al. Autophagy and Female Fertility: Mechanisms, Clinical Implications, and Emerging Therapies[J]. Cells, 2024, 13(16):1354. doi: 10.3390/cells13161354.
[26]	Wu Y, Jiang D, Liu Q, et al. Cathepsin L induces cellular senescence by upregulating CUX1 and p16^INK4a[J]. Aging(Albany NY), 2024, 16(13):10749-10764. doi: 10.18632/aging.205955.
[27]	Pan X, Yu Y, Chen Y, et al. Cathepsin L was involved in vascular aging by mediating phenotypic transformation of vascular cells[J]. Arch Gerontol Geriatr, 2023, 104:104828. doi: 10.1016/j.archger.2022.104828.
[28]	Zhang Y, Li T, Wang Y, et al. Key glycometabolism during oocyte maturation and early embryonic development[J]. Reproduction, 2025, 169(3):e240275. doi: 10.1530/REP-24-0275.
[29]	Moura MT, Latorraca LB, Paula-Lopes FF. Contextualizing Autophagy during Gametogenesis and Preimplantation Embryonic Development[J]. Int J Mol Sci, 2021, 22(12):6313. doi: 10.3390/ijms22126313.
[30]	Weiss-Sadan T, Itzhak G, Kaschani F, et al. Cathepsin L Regulates Metabolic Networks Controlling Rapid Cell Growth and Proliferation[J]. Mol Cell Proteomics, 2019, 18(7):1330-1344. doi: 10.1074/mcp.RA119.001392. pmid: 31010818
[31]	Morin V, Sanchez-Rubio A, Aze A, et al. The protease degrading sperm histones post-fertilization in sea urchin eggs is a nuclear cathepsin L that is further required for embryo development[J]. PLoS One, 2012, 7(11):e46850. doi: 10.1371/journal.pone.0046850.