dc.contributor.author |
Hong, Jiwon |
en |
dc.contributor.author |
Dicker, BL |
en |
dc.contributor.author |
Jayasinghe, SN |
en |
dc.contributor.author |
De Gregorio, F |
en |
dc.contributor.author |
Tian, H |
en |
dc.contributor.author |
Han, DY |
en |
dc.contributor.author |
Hudson, KR |
en |
dc.date.accessioned |
2018-11-14T00:18:05Z |
en |
dc.date.issued |
2017-11 |
en |
dc.identifier.citation |
Biology of Reproduction 97(5):671-687 01 Nov 2017 |
en |
dc.identifier.issn |
0006-3363 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/44245 |
en |
dc.description.abstract |
The vast majority of sperm are lost from the female reproductive tract in hours following natural mating or artificial insemination in mammals. Multiple complex processes including uterine contractions, mucus barriers and phagocytosis of sperm by neutrophils have been reported to be involved in the sperm loss, although the contribution of each process is uncertain. If phagocytosis by neutrophils has a significant role in sperm loss, inhibition of neutrophil response to sperm could potentially reduce the dose of sperm required for artificial insemination. Through development of a quantitative in vitro assay, we have screened 74 candidate compounds for their ability to inhibit the neutrophil-sperm interaction in cattle. Nine inhibitors (GSK2126458, wortmannin, ZSTK474, PIK294, CAL-101, GSK 1059615, GDC-0941, PIK 90 and PI103) active against phosphatidylinositol 3-kinase (PI3-kinase) were most potent, and strongly reduced neutrophil-sperm interaction with an IC50 of 10 nM or less. These inhibitors did not significantly modify sperm motility, and five of the inhibitors did not affect in vitro fertilization. Examination of neutrophil-sperm interaction by time-lapse video microscopy and cell tracking analysis revealed that GSK2126458 may prevent sperm phagocytosis through inhibition of neutrophil movement and/or attachment. Twenty four other compounds exhibited weaker inhibition (IC50 < 115 μM), and the rest did not inhibit the neutrophil-sperm interaction. Strong PI3-kinase inhibitors identified in this study may be useful to determine the contribution of neutrophil phagocytosis in clearance of sperm from the female reproductive tract. |
en |
dc.publisher |
Society for the Study of Reproduction |
en |
dc.relation.ispartofseries |
Biology of Reproduction |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights |
This is a pre-copyedited, author-produced version of an article accepted for publication in Biology of Reproductionfollowing peer review. The version of record is available online at: http://dx.doi.org/10.1093/biolre/iox121 |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://academic.oup.com/journals/pages/access_purchase/rights_and_permissions/self_archiving_policy_b |
en |
dc.title |
Strong inhibition of neutrophil-sperm interaction in cattle by selective PI3-kinase inhibitors |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1093/biolre/iox121 |
en |
pubs.issue |
5 |
en |
pubs.begin-page |
671 |
en |
pubs.volume |
97 |
en |
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
29036279 |
en |
pubs.end-page |
687 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
684903 |
en |
dc.identifier.eissn |
1529-7268 |
en |
pubs.record-created-at-source-date |
2017-10-06 |
en |
pubs.online-publication-date |
2017-10-04 |
en |
pubs.dimensions-id |
29036279 |
en |