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However, the high diagnostic failure rates indicate that the current assessment methods are not sufficient and a new approach to evaluating sperm function still needs to be developed. Here we explored the feasibility of single-cell inductively coupled plasma mass spectrometry (sc-ICP\u2013MS)-derived profiles to determine the elemental characteristics in viable capacitated sperm under normal and deficient conditions. To validate the measurements, we used male sterile Pmca4-knockout (KO) mice with impaired calcium clearance, known to be dysregulated due to loss of calcium efflux capacity during sperm capacitation. Consistently, we observed significantly increased calcium intensities in Pmca4-KO sperm upon capacitation stimulation compared with control sperm from the caudaepididymides of wild-type control (WT) mice. More importantly, we explored that the characteristic signatures of calcium intensities in individual spikes derived from sc-ICP\u2013MS was consistent with the dynamics of relative calcium levels in single sperm reported in the literature. Prominent alterations were also observed in the dynamic signatures of sc-ICP\u2013MS-derived profiles of essential elements, particularly the redox-labile elements including copper, iron, manganese, selenium, and zinc in Pmca4-KO sperm compared to WT controls. Therefore, our study demonstrates that elementomics of sc-ICP\u2013MS-derived signals can reveal ionic dysregulation in plasma membrane Ca2+-ATPase isoform 4 protein deficient sperm, and that sc-ICP\u2013MS assay can be applied for functional analysis of viable sperm in functional activities, such as capacitation stimulation. We propose that cell elementomics can be used as an alternative approach to assessing sperm quality and male fertility at the single-cell level.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfad059","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T08:11:48Z","timestamp":1695456708000},"source":"Crossref","is-referenced-by-count":4,"title":["Dynamic elementomics of single-cell ICP\u2013MS-derived signals in normal and calcium pump PMCA4-deficient mouse epididymal sperm during capacitation"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-3293","authenticated-orcid":false,"given":"Bao Li","family":"Zhang","sequence":"first","affiliation":[{"name":"S , Shanghai 201210 , China"},{"name":"chool of Life Science and Technology, ShanghaiTech University , Shanghai 201210 , China"},{"name":"Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies , Shanghai 200237 , China"},{"name":"Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences , Shanghai 200031 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"S , Shanghai 201210 , China"},{"name":"chool of Life Science and Technology, ShanghaiTech University , Shanghai 201210 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Meng","family":"Shi","sequence":"additional","affiliation":[{"name":"S , Shanghai 201210 , China"},{"name":"chool of Life Science and Technology, ShanghaiTech University , Shanghai 201210 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0324-2470","authenticated-orcid":false,"given":"Hui Juan","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies , Shanghai 200237 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-3703","authenticated-orcid":false,"given":"Patricia A","family":"DeLeon","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware , Newark, DE 19716 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-6097","authenticated-orcid":false,"given":"Winnie","family":"Shum","sequence":"additional","affiliation":[{"name":"S , Shanghai 201210 , China"},{"name":"chool of Life Science and Technology, ShanghaiTech University , Shanghai 201210 , China"},{"name":"Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies , Shanghai 200237 , China"},{"name":"Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences , Shanghai 200031 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"issue":"5","key":"2024012010382787800_bib1","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.fertnstert.2009.09.009","article-title":"International Committee for Monitoring Assisted Reproductive T, World Health O. 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