Hostname: page-component-669899f699-7tmb6 Total loading time: 0 Render date: 2025-04-30T21:06:08.874Z Has data issue: false hasContentIssue false
  • English
  • Français

Overexpression of PD-L1 causes germ cell failure and infertility via CRISP1/PD-L1 interaction in mouse epididymis

Published online by Cambridge University Press:  03 June 2024

Ting Li  and
Hongmin Guo Open the ORCID record for Hongmin Guo [Opens in a new window]
Ting Li
Affiliation:
School of Food and Bioengineering, Wuhu Institute of Technology, Wuhu, China
Hongmin Guo*
Affiliation:
Department of Reproductive Medicine, Liaocheng People’s Hospital, Liaocheng, China
*
Corresponding author: Hongmin Guo; Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Spermatogenesis is a highly complex process through which mature sperms are produced, and it requires three important stages; mitosis, meiosis and sperm formation. The expression of genes regulated by transcription factors at specific stages exerts important regulatory effects on the development process of germ cells. Male mice with overexpressed programmed death ligand 1 (PD-L1) (B7 homolog1) in the testis have infertility and abnormal sperm development, thereby exhibiting severe malformation and sloughing throughout spermatid maturation and collapsed and disorganized seminiferous epithelium structure. Furthermore, PD-L1 overexpression causes overexpression of cysteine-rich secretory protein 1 (CRISP1) in the epididymis and adversely affects or precludes sperm energization, sperm-pellucida binding and sperm-oocyte fusion. These findings suggest that CRISP1 and PD-L1 can interact with each other to induce male infertility and germ-cell dissociation.

Keywords

cysteine-rich secretory protein 1germ cellsprogrammed death ligand 1programmed death ligand 1/cysteine-rich secretory protein 1transgenic
Type
Research Article
Information
Zygote , Volume 32 , Issue 3 , June 2024 , pp. 224 - 229
Check for updates
Copyright
© The Author(s), 2024. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Arévalo, L., Brukman, N.G., Cuasnicú, P.S. and Roldan, E.R.S. (2020) Evolutionary analysis of genes coding for Cysteine-RIch Secretory Proteins (CRISPs) in mammals. BMC Evolutionary Biology 20, 67. https://doi.org/10.1186/s12862-020-01632-5.CrossRefGoogle ScholarPubMed
Cameo, M.S. and Blaquier, J.A. (1976) Androgen-controlled specific proteins in rat epididymis. The Journal of Endocrinology 69, 47–55. https://doi.org/10.1677/joe.0.0690047.CrossRefGoogle Scholar
Claw, K.G., George, R.D. and Swanson, W.J. (2014) Detecting coevolution in mammalian sperm-egg fusion proteins. Molecular Reproduction and Development 81, 531–538. https://doi.org/10.1002/mrd.22321.CrossRefGoogle Scholar
Curci, L., Brukman, N.G., Weigel Muñoz, M., Rojo, D., Carvajal, G., Sulzyk, V., Gonzalez, S.N., Rubinstein, M., Da Ros, V.G. and Cuasnicú, P.S. (2020) Functional redundancy and compensation: deletion of multiple murine Crisp genes reveals their essential role for male fertility. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 34, 15718–15733. https://doi.org/10.1096/fj.202001406R.CrossRefGoogle Scholar
Da Ros, V.G., Muñoz, M.W., Battistone, M.A., Brukman, N.G., Carvajal, G., Curci, L., Gómez-ElIas, M.D., Cohen, D.B. and Cuasnicu, P.S. (2015) From the epididymis to the egg: participation of CRISP proteins in mammalian fertilization. Asian Journal of Andrology 17, 711–715. https://doi.org/10.4103/1008-682X.155769.Google Scholar
Ernesto, J.I., Weigel Muñoz, M., Battistone, M.A., Vasen, G., Martínez-López, P., Orta, G., Figueiras-Fierro, D., De la Vega-Beltran, J.L., Moreno, I.A., Guidobaldi, H.A., Giojalas, L., Darszon, A., Cohen, D.J. and Cuasnicú, P.S. (2015) CRISP1 as a novel CatSper regulator that modulates sperm motility and orientation during fertilization. The Journal of Cell Biology 210, 1213–1224. https://doi.org/10.1083/jcb.201412041.CrossRefGoogle ScholarPubMed
Fang, L., Feng, R., Liang, W., Liu, F.F., Bian, G.L., Yu, C., Guo, H., Cao, Y., Liu, M., Zuo, J., Peng, Y., Zhao, J., Sun, R.X., Shan, J. and Wang, J. (2022) Overexpression of PD-L1 causes germ cells to slough from mouse seminiferous tubules via the PD-L1/PD-L1 interaction. Journal of Cellular and Molecular Medicine 26, 2908–2920. https://doi.org/10.1111/jcmm.17305.CrossRefGoogle Scholar
Freeman, G.J., Long, A.J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L.J., Malenkovich, N., Okazaki, T., Byrne, M.C., Horton, H.F., Fouser, L., Carter, L., Ling, V., Bowman, M.R., Carreno, B.M., Collins, M., Wood, C.R. and Honjo, T. (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of Experimental Medicine 192, 1027–1034. https://doi.org/10.1084/jem.192.7.1027.CrossRefGoogle Scholar
Gaikwad, A.S., Nandagiri, A., Potter, D.L., Nosrati, R., O’Connor, A.E., Jadhav, S., Soria, J., Prabhakar, R. and O’Bryan, M.K. (2021) CRISPs function to boost sperm power output and motility. Frontiers in Cell and Developmental Biology 9, 693258. https://doi.org/10.3389/fcell.2021.693258.CrossRefGoogle Scholar
Giacomini, E., Makieva, S., Murdica, V., Vago, R. and Viganó, P. (2020) Extracellular vesicles as a potential diagnostic tool in assisted reproduction. Current Opinion in Obstetrics & Gynecology 32, 179–184. https://doi.org/10.1097/GCO.0000000000000621.CrossRefGoogle Scholar
Hu, J., Merriner, D.J., O’Connor, A.E., Houston, B.J., Furic, L., Hedger, M.P. and O’Bryan, M.K. (2018) Epididymal cysteine-rich secretory proteins are required for epididymal sperm maturation and optimal sperm function. Molecular Human Reproduction 24, 111–122. https://doi.org/10.1093/molehr/gay001.CrossRefGoogle Scholar
Lv, Z.M., Ling, M.Y. and Chen, C. (2020) Comparative proteomics reveals protective effect of resveratrol on a high-fat diet-induced damage to mice testis. Systems Biology in Reproductive Medicine 66, 37–49. https://doi.org/10.1080/19396368.2019.1701138.CrossRefGoogle Scholar
Ikawa, M., Inoue, N., Benham, A.M. and Okabe, M. (2010) Fertilization: a sperm’s journey to and interaction with the oocyte. The Journal of Clinical Investigation 120, 984–994. https://doi.org/10.1172/JCI41585.CrossRefGoogle Scholar
Jansen, V., Alvarez, L., Balbach, M., Strünker, T., Hegemann, P., Kaupp, U.B. and Wachten, D. (2015) Controlling fertilization and cAMP signaling in sperm by optogenetics. eLife 4, e05161. https://doi.org/10.7554/eLife.05161.CrossRefGoogle Scholar
Jorasia, K., Paul, R.K., Rathore, N.S., Lal, P., Singh, R. and Sareen, M. (2021) Production of bioactive recombinant ovine cysteine-rich secretory protein 1 in Escherichia coli. Systems Biology in Reproductive Medicine 67, 471–481. https://doi.org/10.1080/19396368.2021.1963012.CrossRefGoogle Scholar
Martinez, C.A., Alvarez-Rodriguez, M., Wright, D. and Rodriguez-Martinez, H. (2020) Does the pre-ovulatory pig oviduct rule sperm capacitation in vivo mediating transcriptomics of Catsper channels?. International Journal of Molecular Sciences 21, 1840. https://doi.org/10.3390/ijms21051840.CrossRefGoogle Scholar
Matamoros-Volante, A., Moreno-Irusta, A., Torres-Rodriguez, P., Giojalas, L., Gervasi, M.G., Visconti, P.E. and Treviño, C.L. (2018) Semi-automatized segmentation method using image-based flow cytometry to study sperm physiology: the case of capacitation-induced tyrosine phosphorylation. Molecular Human Reproduction 24, 64–73. https://doi.org/10.1093/molehr/gax062.CrossRefGoogle Scholar
Nigro, P., Middelbeek, R.J.W., Alves, C.R.R., Rovira-Llopis, S., Ramachandran, K., Rowland, L.A., Møller, A.B., Takahashi, H., Alves-Wagner, A.B., Vamvini, M., Makarewicz, N.S., Albertson, B.G., Hirshman, M.F. and Goodyear, L.J. (2021) Exercise training promotes sex-specific adaptations in mouse inguinal white adipose tissue. Diabetes 70, 1250–1264. https://doi.org/10.2337/db20-0790.CrossRefGoogle Scholar
Roberts, K.P., Ensrud-Bowlin, K.M., Piehl, L.B., Parent, K.R., Bernhardt, M.L. and Hamilton, D.W. (2008) Association of the protein D and protein E forms of rat CRISP1 with epididymal sperm. Biology of Reproduction 79, 1046–1053. https://doi.org/10.1095/biolreprod.108.070664.CrossRefGoogle Scholar
Roberts, K.P., Johnston, D.S., Nolan, M.A., Wooters, J.L., Waxmonsky, N.C., Piehl, L.B., Ensrud-Bowlin, K.M. and Hamilton, D.W. (2007) Structure and function of epididymal protein cysteine-rich secretory protein-1. Asian Journal of Andrology 9, 508–514. https://doi.org/10.1111/j.1745-7262.2007.00318.x.CrossRefGoogle Scholar
Sheng, J., Gadella, B.M., Olrichs, N.K., Kaloyanova, D.V. and Helms, J.B. (2021) The less conserved metal-binding site in human CRISP1 remains sensitive to zinc ions to permit protein oligomerization. Scientific Reports 11, 5498. https://doi.org/10.1038/s41598-021-84926-y.CrossRefGoogle Scholar
Skinner, M.K. (1991) Cell-cell interactions in the testis. Endocrine Reviews 12, 45–77. https://doi.org/10.1210/edrv-12-1-45.CrossRefGoogle Scholar
Sun, C., Mezzadra, R. and Schumacher, T.N. (2018) Regulation and function of the PD-L1 Checkpoint. Immunity 48, 434–452. https://doi.org/10.1016/j.immuni.2018.03.014.CrossRefGoogle Scholar
Weigel Muñoz, M., Battistone, M.A., Carvajal, G., Maldera, J.A., Curci, L., Torres, P., Lombardo, D., Pignataro, O.P., Da Ros, V.G. and Cuasnicú, P.S. (2018) Influence of the genetic background on the reproductive phenotype of mice lacking Cysteine-Rich Secretory Protein 1 (CRISP1). Biology of Reproduction 99, 373–383. https://doi.org/10.1093/biolre/ioy048.CrossRefGoogle Scholar