Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.

Female-controlled contraception/HIV prevention is critical to address health issues associated with gender inequality. Therefore, a contraceptive which can be administered in tandem with a microbicide to inhibit sexually transmitted infections, is desirable. Uterine leukemia inhibitory factor (LIF)...

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Autores principales: Ellen Menkhorst, Jian-Guo Zhang, Natalie A Sims, Phillip O Morgan, Priscilla Soo, Ingrid J Poulton, Donald Metcalf, Estella Alexandrou, Melissa Gresle, Lois A Salamonsen, Helmut Butzkueven, Nicos A Nicola, Evdokia Dimitriadis
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:f40a3cc926b847cd89f540b04900a6702021-11-18T06:53:49ZVaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.1932-620310.1371/journal.pone.0019665https://doaj.org/article/f40a3cc926b847cd89f540b04900a6702011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21611124/?tool=EBIhttps://doaj.org/toc/1932-6203Female-controlled contraception/HIV prevention is critical to address health issues associated with gender inequality. Therefore, a contraceptive which can be administered in tandem with a microbicide to inhibit sexually transmitted infections, is desirable. Uterine leukemia inhibitory factor (LIF) is obligatory for blastocyst implantation in mice and associated with infertility in women. We aimed to determine whether a PEGylated LIF inhibitor (PEGLA) was an effective contraceptive following vaginal delivery and to identify non-uterine targets of PEGLA in mice.Vaginally-applied (125)I-PEGLA accumulated in blood more slowly (30 min vs 10 min) and showed reduced tissue and blood retention (24 h vs 96 h) compared to intraperitoneal injection in mice. Vaginally-applied PEGLA blocked implantation. PEGLA administered by intraperitoneal injection inhibited bone remodelling whereas vaginally-applied PEGLA had no effect on bone. Further, PEGLA had no effect in an animal model of multiple sclerosis, experimental auto-immune encephalomyelitis, suggesting PEGLA cannot target the central nervous system.Vaginally-administered PEGLA is a promising non-hormonal contraceptive, one which could be delivered alone, or in tandem with a microbicide. Vaginal application reduced the total dose of PEGLA required to block implantation and eliminated the systemic effect on bone, showing the vagina is a promising site of administration for larger drugs which target organs within the reproductive tract.Ellen MenkhorstJian-Guo ZhangNatalie A SimsPhillip O MorganPriscilla SooIngrid J PoultonDonald MetcalfEstella AlexandrouMelissa GresleLois A SalamonsenHelmut ButzkuevenNicos A NicolaEvdokia DimitriadisEvdokia DimitriadisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19665 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ellen Menkhorst
Jian-Guo Zhang
Natalie A Sims
Phillip O Morgan
Priscilla Soo
Ingrid J Poulton
Donald Metcalf
Estella Alexandrou
Melissa Gresle
Lois A Salamonsen
Helmut Butzkueven
Nicos A Nicola
Evdokia Dimitriadis
Evdokia Dimitriadis
Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.
description Female-controlled contraception/HIV prevention is critical to address health issues associated with gender inequality. Therefore, a contraceptive which can be administered in tandem with a microbicide to inhibit sexually transmitted infections, is desirable. Uterine leukemia inhibitory factor (LIF) is obligatory for blastocyst implantation in mice and associated with infertility in women. We aimed to determine whether a PEGylated LIF inhibitor (PEGLA) was an effective contraceptive following vaginal delivery and to identify non-uterine targets of PEGLA in mice.Vaginally-applied (125)I-PEGLA accumulated in blood more slowly (30 min vs 10 min) and showed reduced tissue and blood retention (24 h vs 96 h) compared to intraperitoneal injection in mice. Vaginally-applied PEGLA blocked implantation. PEGLA administered by intraperitoneal injection inhibited bone remodelling whereas vaginally-applied PEGLA had no effect on bone. Further, PEGLA had no effect in an animal model of multiple sclerosis, experimental auto-immune encephalomyelitis, suggesting PEGLA cannot target the central nervous system.Vaginally-administered PEGLA is a promising non-hormonal contraceptive, one which could be delivered alone, or in tandem with a microbicide. Vaginal application reduced the total dose of PEGLA required to block implantation and eliminated the systemic effect on bone, showing the vagina is a promising site of administration for larger drugs which target organs within the reproductive tract.
format article
author Ellen Menkhorst
Jian-Guo Zhang
Natalie A Sims
Phillip O Morgan
Priscilla Soo
Ingrid J Poulton
Donald Metcalf
Estella Alexandrou
Melissa Gresle
Lois A Salamonsen
Helmut Butzkueven
Nicos A Nicola
Evdokia Dimitriadis
Evdokia Dimitriadis
author_facet Ellen Menkhorst
Jian-Guo Zhang
Natalie A Sims
Phillip O Morgan
Priscilla Soo
Ingrid J Poulton
Donald Metcalf
Estella Alexandrou
Melissa Gresle
Lois A Salamonsen
Helmut Butzkueven
Nicos A Nicola
Evdokia Dimitriadis
Evdokia Dimitriadis
author_sort Ellen Menkhorst
title Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.
title_short Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.
title_full Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.
title_fullStr Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.
title_full_unstemmed Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.
title_sort vaginally administered pegylated lif antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/f40a3cc926b847cd89f540b04900a670
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