{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:11:10Z","timestamp":1789258270293,"version":"build-2803163510"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["6071\/2-1"],"award-info":[{"award-number":["6071\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infertility represents a major global health challenge and has driven increasing reliance on ART. However, fertilization success in vitro is often limited when physiological egg\u2013sperm interaction is preserved, largely due to premature hardening of the zona pellucida (ZP), the extracellular matrix surrounding the oocyte that controls sperm access. ZP hardening is physiologically triggered after fertilization by ovastacin-mediated cleavage of ZP protein 2 (ZP2) to protect the early embryo. However, if not inhibited prematurely, this cleavage reduces egg competence. In vivo, ovastacin is restrained by the plasma protein fetuin-B, largely absent in IVF media. Whether this process can be pharmacologically targeted has yet to be explored. Here, we identify and functionally characterize small-molecule hydroxamate inhibitors that transiently inhibit ovastacin in murine oocytes and evaluate their ability to control fertilization competence. A lead compound preserved ZP2 integrity and fertilization rates at 86% (\u00b11%) after 8\u2009h of in vitro culture, compared to 57% (\u00b17%) in controls. Importantly, inhibitor-treated embryos developed to the blastocyst stage without abnormalities. These findings establish transient ovastacin inhibition as simple, non-invasive pharmacological strategy to ensure IVF outcomes while preserving physiological egg\u2013sperm interaction mechanisms.<\/jats:p>","DOI":"10.1093\/molehr\/gaag041","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:34:07Z","timestamp":1782992047000},"source":"Crossref","is-referenced-by-count":0,"title":["Small-molecule ovastacin inhibitors preserve fertilization competence of murine eggs by mimicking fetuin-B function"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1816-0769","authenticated-orcid":false,"given":"Nele","family":"von Wiegen","sequence":"first","affiliation":[{"name":"Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Sch\u00f6mbs","sequence":"additional","affiliation":[{"name":"Translational Animal Research Center, University Medical Center of the Johannes Gutenberg University , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander Moldt","family":"Haack","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biomedicine, Technical University of Denmark , Kongens Lyngby,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt , Frankfurt am Main,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Tan","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn , Bonn,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University , Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1315-4407","authenticated-orcid":false,"given":"Willi","family":"Jahnen-Dechent","sequence":"additional","affiliation":[{"name":"Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University , Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albrecht Martin","family":"Clement","sequence":"additional","affiliation":[{"name":"Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4462-1776","authenticated-orcid":false,"given":"Julia","family":"Floehr","sequence":"additional","affiliation":[{"name":"Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University , Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-2378","authenticated-orcid":false,"given":"Christian","family":"Behl","sequence":"additional","affiliation":[{"name":"Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-8432","authenticated-orcid":false,"given":"Stefan","family":"Tasler","sequence":"additional","affiliation":[{"name":"Vivoryon Therapeutics N.V. , Halle (Saale),","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6518-3344","authenticated-orcid":false,"given":"Claudia","family":"Tredup","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt , Frankfurt am Main,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Baska","sequence":"additional","affiliation":[{"name":"Translational Animal Research Center, University Medical Center of the Johannes Gutenberg University , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4966-142X","authenticated-orcid":false,"given":"Daniel","family":"Ramsbeck","sequence":"additional","affiliation":[{"name":"Department of Applied Biosciences and Process Technology, Anhalt University of Applied Sciences , K\u00f6then,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-2669","authenticated-orcid":false,"given":"Hagen","family":"K\u00f6rschgen","sequence":"additional","affiliation":[{"name":"Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"2026091219462933000_gaag041-B1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.fertnstert.2025.02.009","article-title":"How many infants have been born with the help of assisted reproductive technology?","volume":"124","author":"Adamson","year":"2025","journal-title":"Fertil Steril"},{"key":"2026091219462933000_gaag041-B2","doi-asserted-by":"crossref","first-page":"336ra60","DOI":"10.1126\/scitranslmed.aad9946","article-title":"ZP2 peptide beads 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