A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques

Autores
Peluffo, Marina Cinthia; Stanley, J.; Braeuer, N.; Rotgeri, A.; Fritzemeier, K. H.; Fuhrmann, U.; Buchmann, B.; Adevai, T.; Murphy, M. J.; Zelinski, M. B.; Lindenthal, B.; Hennebold, J. D.; Stouffer, R. L.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
STUDY QUESTION Can administration of a prostaglandin (PG) E2 receptor 2 (PTGER2) antagonist prevent pregnancy in adult female monkeys by blocking periovulatory events in the follicle without altering menstrual cyclicity or general health? SUMMARY ANSWER This is the first study to demonstrate that a PTGER2 antagonist can serve as an effective non-hormonal contraceptive in primates. WHAT IS KNOWN ALREADY The requirement for PGE2 in ovulation and the release of an oocyte surrounded by expanded cumulus cells (cumulus–oocyte expansion; C-OE) was established through the generation of PTGS2 and PTGER2 null-mutant mice. A critical role for PGE2 in primate ovulation is supported by evidence that intrafollicular injection of indomethacin in rhesus monkeys suppressed follicle rupture, whereas co-injection of PGE2 with indomethacin resulted in ovulation. STUDY DESIGN, SIZE, DURATION First, controlled ovulation protocols were performed in adult, female rhesus monkeys to analyze the mRNA levels for genes encoding PGE2 synthesis and signaling components in the naturally selected pre-ovulatory follicle at different times after the ovulatory hCG stimulus (0, 12, 24, 36 h pre-ovulation; 36 h post-ovulation, n = 3–4/time point). Second, controlled ovarian stimulation cycles were utilized to obtain multiple cumulus–oocyte complexes (COCs) from rhesus monkeys to evaluate the role of PGE2 in C-OE in vitro (n = 3–4 animals/treatment; ≥3 COCs/animal/treatment). Third, adult cycling female cynomolgus macaques were randomly assigned (n = 10/group) to vehicle (control) or PTGER2 antagonist (BAY06) groups to perform a contraceptive trial. After the first treatment cycle, a male of proven fertility was introduced into each group and they remained housed together for the duration of the 5-month contraceptive trial that was followed by a post-treatment reversibility trial. PARTICIPANTS/MATERIALS, SETTING, METHODS Quantitative real-time PCR, COC culture and expansion, immunofluorescence/confocal microscopy, enzyme immunoassay, contraceptive trial, ultrasonography, complete blood counts, serum biochemistry tests and blood lipid profiles. MAIN RESULTS AND THE ROLE OF CHANCE Several mRNAs encoding proteins involved in PGE2 synthesis, metabolism and signaling increase (P < 0.05) in the periovulatory follicle after administration of an ovulatory hCG bolus. PGE2 signaling through PTGER2 induces cumulus cell expansion and production of hyaluronic acid, which are critical events for fertilization. Moreover, chronic administration of a selective PTGER2 antagonist resulted in a significant (P < 0.05 versus vehicle-treated controls) contraceptive effect without altering steroid hormone patterns or menstrual cyclicity during a 5-months contraceptive trial. Fertility recovered as early as 1 month after ending treatment. LIMITATIONS, REASONS FOR CAUTION This is a proof-of-concept study in a non-human primate model. Further investigations are warranted to elucidate the mechanism(s) of PTGER2 antagonist action in the primate ovary. Although PTGER2 antagonist treatment did not produce any obvious undesirable effects, improvements in the mode of administration, as well as the efficacy of these compounds, are necessary to consider such a contraceptive for women. WIDER IMPLICATIONS OF THE FINDINGS Monitoring as well as improving the efficacy and safety of female contraceptives is an important public health activity. Even though hormonal contraceptives are effective for women, concerns remain regarding their side-effects and long-term use because of the widespread actions of such steroidal products in many tissues. Moreover, some women cannot take hormones for medical reasons. Thus, development of non-hormonal contraceptives for women is warranted. STUDY FUNDING/COMPETING INTEREST(S) Supported by Bayer HealthCare Pharmaceuticals, The Eunice Kennedy Shriver NICHD Contraceptive Development and Research Center (U54 HD055744), NIH Office of the Director (Oregon National Primate Research Center P51 OD011092), and a Lalor Foundation Postdoctoral Basic Research Fellowship (MCP). The use of the Leica confocal was supported by grant number S10RR024585. Some of the authors (N.B., A.R., K.-H.F., U.F., B.B. and B.L.) are employees of Bayer Healthcare Pharma.
Fil: Peluffo, Marina Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Stanley, J.. Oregon National Primate Research Center; Estados Unidos
Fil: Braeuer, N.. Bayer Healthcare Pharma; Alemania
Fil: Rotgeri, A.. Bayer Healthcare Pharma; Alemania
Fil: Fritzemeier, K. H.. Universitat Duisburg - Essen; Alemania
Fil: Fuhrmann, U.. Bayer Healthcare Pharma; Alemania
Fil: Buchmann, B.. Bayer Healthcare Pharma; Alemania
Fil: Adevai, T.. Oregon National Primate Research Center; Estados Unidos
Fil: Murphy, M. J.. Oregon National Primate Research Center; Estados Unidos
Fil: Zelinski, M. B.. Oregon Health and Science University; Estados Unidos
Fil: Lindenthal, B.. Bayer Healthcare Pharma; Alemania
Fil: Hennebold, J. D.. Oregon National Primate Research Center; Estados Unidos. Oregon Health and Science University; Estados Unidos
Fil: Stouffer, R. L.. Oregon National Primate Research Center; Estados Unidos. Oregon Health and Science University; Estados Unidos
Materia
Prostaglandin E2 Receptor
Cumulus Oocyte Expansion
Contraceptive Trial
Primates
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8189

id CONICETDig_0881238d5b3e2ae9ddfcd4efc091a2b8
oai_identifier_str oai:ri.conicet.gov.ar:11336/8189
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaquesPeluffo, Marina CinthiaStanley, J.Braeuer, N.Rotgeri, A.Fritzemeier, K. H.Fuhrmann, U.Buchmann, B.Adevai, T.Murphy, M. J.Zelinski, M. B.Lindenthal, B.Hennebold, J. D.Stouffer, R. L.Prostaglandin E2 ReceptorCumulus Oocyte ExpansionContraceptive TrialPrimateshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3STUDY QUESTION Can administration of a prostaglandin (PG) E2 receptor 2 (PTGER2) antagonist prevent pregnancy in adult female monkeys by blocking periovulatory events in the follicle without altering menstrual cyclicity or general health? SUMMARY ANSWER This is the first study to demonstrate that a PTGER2 antagonist can serve as an effective non-hormonal contraceptive in primates. WHAT IS KNOWN ALREADY The requirement for PGE2 in ovulation and the release of an oocyte surrounded by expanded cumulus cells (cumulus–oocyte expansion; C-OE) was established through the generation of PTGS2 and PTGER2 null-mutant mice. A critical role for PGE2 in primate ovulation is supported by evidence that intrafollicular injection of indomethacin in rhesus monkeys suppressed follicle rupture, whereas co-injection of PGE2 with indomethacin resulted in ovulation. STUDY DESIGN, SIZE, DURATION First, controlled ovulation protocols were performed in adult, female rhesus monkeys to analyze the mRNA levels for genes encoding PGE2 synthesis and signaling components in the naturally selected pre-ovulatory follicle at different times after the ovulatory hCG stimulus (0, 12, 24, 36 h pre-ovulation; 36 h post-ovulation, n = 3–4/time point). Second, controlled ovarian stimulation cycles were utilized to obtain multiple cumulus–oocyte complexes (COCs) from rhesus monkeys to evaluate the role of PGE2 in C-OE in vitro (n = 3–4 animals/treatment; ≥3 COCs/animal/treatment). Third, adult cycling female cynomolgus macaques were randomly assigned (n = 10/group) to vehicle (control) or PTGER2 antagonist (BAY06) groups to perform a contraceptive trial. After the first treatment cycle, a male of proven fertility was introduced into each group and they remained housed together for the duration of the 5-month contraceptive trial that was followed by a post-treatment reversibility trial. PARTICIPANTS/MATERIALS, SETTING, METHODS Quantitative real-time PCR, COC culture and expansion, immunofluorescence/confocal microscopy, enzyme immunoassay, contraceptive trial, ultrasonography, complete blood counts, serum biochemistry tests and blood lipid profiles. MAIN RESULTS AND THE ROLE OF CHANCE Several mRNAs encoding proteins involved in PGE2 synthesis, metabolism and signaling increase (P < 0.05) in the periovulatory follicle after administration of an ovulatory hCG bolus. PGE2 signaling through PTGER2 induces cumulus cell expansion and production of hyaluronic acid, which are critical events for fertilization. Moreover, chronic administration of a selective PTGER2 antagonist resulted in a significant (P < 0.05 versus vehicle-treated controls) contraceptive effect without altering steroid hormone patterns or menstrual cyclicity during a 5-months contraceptive trial. Fertility recovered as early as 1 month after ending treatment. LIMITATIONS, REASONS FOR CAUTION This is a proof-of-concept study in a non-human primate model. Further investigations are warranted to elucidate the mechanism(s) of PTGER2 antagonist action in the primate ovary. Although PTGER2 antagonist treatment did not produce any obvious undesirable effects, improvements in the mode of administration, as well as the efficacy of these compounds, are necessary to consider such a contraceptive for women. WIDER IMPLICATIONS OF THE FINDINGS Monitoring as well as improving the efficacy and safety of female contraceptives is an important public health activity. Even though hormonal contraceptives are effective for women, concerns remain regarding their side-effects and long-term use because of the widespread actions of such steroidal products in many tissues. Moreover, some women cannot take hormones for medical reasons. Thus, development of non-hormonal contraceptives for women is warranted. STUDY FUNDING/COMPETING INTEREST(S) Supported by Bayer HealthCare Pharmaceuticals, The Eunice Kennedy Shriver NICHD Contraceptive Development and Research Center (U54 HD055744), NIH Office of the Director (Oregon National Primate Research Center P51 OD011092), and a Lalor Foundation Postdoctoral Basic Research Fellowship (MCP). The use of the Leica confocal was supported by grant number S10RR024585. Some of the authors (N.B., A.R., K.-H.F., U.F., B.B. and B.L.) are employees of Bayer Healthcare Pharma.Fil: Peluffo, Marina Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Stanley, J.. Oregon National Primate Research Center; Estados UnidosFil: Braeuer, N.. Bayer Healthcare Pharma; AlemaniaFil: Rotgeri, A.. Bayer Healthcare Pharma; AlemaniaFil: Fritzemeier, K. H.. Universitat Duisburg - Essen; AlemaniaFil: Fuhrmann, U.. Bayer Healthcare Pharma; AlemaniaFil: Buchmann, B.. Bayer Healthcare Pharma; AlemaniaFil: Adevai, T.. Oregon National Primate Research Center; Estados UnidosFil: Murphy, M. J.. Oregon National Primate Research Center; Estados UnidosFil: Zelinski, M. B.. Oregon Health and Science University; Estados UnidosFil: Lindenthal, B.. Bayer Healthcare Pharma; AlemaniaFil: Hennebold, J. D.. Oregon National Primate Research Center; Estados Unidos. Oregon Health and Science University; Estados UnidosFil: Stouffer, R. L.. Oregon National Primate Research Center; Estados Unidos. Oregon Health and Science University; Estados UnidosOxford University Press2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8189Peluffo, Marina Cinthia; Stanley, J.; Braeuer, N.; Rotgeri, A.; Fritzemeier, K. H.; et al.; A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques; Oxford University Press; Human Reproduction; 29; 7; 3-2014; 1400-14120268-1161enginfo:eu-repo/semantics/altIdentifier/url/http://humrep.oxfordjournals.org/content/29/7/1400.longinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059334/info:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/deu083info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:15Zoai:ri.conicet.gov.ar:11336/8189instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:47:15.726CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
title A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
spellingShingle A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
Peluffo, Marina Cinthia
Prostaglandin E2 Receptor
Cumulus Oocyte Expansion
Contraceptive Trial
Primates
title_short A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
title_full A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
title_fullStr A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
title_full_unstemmed A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
title_sort A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques
dc.creator.none.fl_str_mv Peluffo, Marina Cinthia
Stanley, J.
Braeuer, N.
Rotgeri, A.
Fritzemeier, K. H.
Fuhrmann, U.
Buchmann, B.
Adevai, T.
Murphy, M. J.
Zelinski, M. B.
Lindenthal, B.
Hennebold, J. D.
Stouffer, R. L.
author Peluffo, Marina Cinthia
author_facet Peluffo, Marina Cinthia
Stanley, J.
Braeuer, N.
Rotgeri, A.
Fritzemeier, K. H.
Fuhrmann, U.
Buchmann, B.
Adevai, T.
Murphy, M. J.
Zelinski, M. B.
Lindenthal, B.
Hennebold, J. D.
Stouffer, R. L.
author_role author
author2 Stanley, J.
Braeuer, N.
Rotgeri, A.
Fritzemeier, K. H.
Fuhrmann, U.
Buchmann, B.
Adevai, T.
Murphy, M. J.
Zelinski, M. B.
Lindenthal, B.
Hennebold, J. D.
Stouffer, R. L.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Prostaglandin E2 Receptor
Cumulus Oocyte Expansion
Contraceptive Trial
Primates
topic Prostaglandin E2 Receptor
Cumulus Oocyte Expansion
Contraceptive Trial
Primates
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv STUDY QUESTION Can administration of a prostaglandin (PG) E2 receptor 2 (PTGER2) antagonist prevent pregnancy in adult female monkeys by blocking periovulatory events in the follicle without altering menstrual cyclicity or general health? SUMMARY ANSWER This is the first study to demonstrate that a PTGER2 antagonist can serve as an effective non-hormonal contraceptive in primates. WHAT IS KNOWN ALREADY The requirement for PGE2 in ovulation and the release of an oocyte surrounded by expanded cumulus cells (cumulus–oocyte expansion; C-OE) was established through the generation of PTGS2 and PTGER2 null-mutant mice. A critical role for PGE2 in primate ovulation is supported by evidence that intrafollicular injection of indomethacin in rhesus monkeys suppressed follicle rupture, whereas co-injection of PGE2 with indomethacin resulted in ovulation. STUDY DESIGN, SIZE, DURATION First, controlled ovulation protocols were performed in adult, female rhesus monkeys to analyze the mRNA levels for genes encoding PGE2 synthesis and signaling components in the naturally selected pre-ovulatory follicle at different times after the ovulatory hCG stimulus (0, 12, 24, 36 h pre-ovulation; 36 h post-ovulation, n = 3–4/time point). Second, controlled ovarian stimulation cycles were utilized to obtain multiple cumulus–oocyte complexes (COCs) from rhesus monkeys to evaluate the role of PGE2 in C-OE in vitro (n = 3–4 animals/treatment; ≥3 COCs/animal/treatment). Third, adult cycling female cynomolgus macaques were randomly assigned (n = 10/group) to vehicle (control) or PTGER2 antagonist (BAY06) groups to perform a contraceptive trial. After the first treatment cycle, a male of proven fertility was introduced into each group and they remained housed together for the duration of the 5-month contraceptive trial that was followed by a post-treatment reversibility trial. PARTICIPANTS/MATERIALS, SETTING, METHODS Quantitative real-time PCR, COC culture and expansion, immunofluorescence/confocal microscopy, enzyme immunoassay, contraceptive trial, ultrasonography, complete blood counts, serum biochemistry tests and blood lipid profiles. MAIN RESULTS AND THE ROLE OF CHANCE Several mRNAs encoding proteins involved in PGE2 synthesis, metabolism and signaling increase (P < 0.05) in the periovulatory follicle after administration of an ovulatory hCG bolus. PGE2 signaling through PTGER2 induces cumulus cell expansion and production of hyaluronic acid, which are critical events for fertilization. Moreover, chronic administration of a selective PTGER2 antagonist resulted in a significant (P < 0.05 versus vehicle-treated controls) contraceptive effect without altering steroid hormone patterns or menstrual cyclicity during a 5-months contraceptive trial. Fertility recovered as early as 1 month after ending treatment. LIMITATIONS, REASONS FOR CAUTION This is a proof-of-concept study in a non-human primate model. Further investigations are warranted to elucidate the mechanism(s) of PTGER2 antagonist action in the primate ovary. Although PTGER2 antagonist treatment did not produce any obvious undesirable effects, improvements in the mode of administration, as well as the efficacy of these compounds, are necessary to consider such a contraceptive for women. WIDER IMPLICATIONS OF THE FINDINGS Monitoring as well as improving the efficacy and safety of female contraceptives is an important public health activity. Even though hormonal contraceptives are effective for women, concerns remain regarding their side-effects and long-term use because of the widespread actions of such steroidal products in many tissues. Moreover, some women cannot take hormones for medical reasons. Thus, development of non-hormonal contraceptives for women is warranted. STUDY FUNDING/COMPETING INTEREST(S) Supported by Bayer HealthCare Pharmaceuticals, The Eunice Kennedy Shriver NICHD Contraceptive Development and Research Center (U54 HD055744), NIH Office of the Director (Oregon National Primate Research Center P51 OD011092), and a Lalor Foundation Postdoctoral Basic Research Fellowship (MCP). The use of the Leica confocal was supported by grant number S10RR024585. Some of the authors (N.B., A.R., K.-H.F., U.F., B.B. and B.L.) are employees of Bayer Healthcare Pharma.
Fil: Peluffo, Marina Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Stanley, J.. Oregon National Primate Research Center; Estados Unidos
Fil: Braeuer, N.. Bayer Healthcare Pharma; Alemania
Fil: Rotgeri, A.. Bayer Healthcare Pharma; Alemania
Fil: Fritzemeier, K. H.. Universitat Duisburg - Essen; Alemania
Fil: Fuhrmann, U.. Bayer Healthcare Pharma; Alemania
Fil: Buchmann, B.. Bayer Healthcare Pharma; Alemania
Fil: Adevai, T.. Oregon National Primate Research Center; Estados Unidos
Fil: Murphy, M. J.. Oregon National Primate Research Center; Estados Unidos
Fil: Zelinski, M. B.. Oregon Health and Science University; Estados Unidos
Fil: Lindenthal, B.. Bayer Healthcare Pharma; Alemania
Fil: Hennebold, J. D.. Oregon National Primate Research Center; Estados Unidos. Oregon Health and Science University; Estados Unidos
Fil: Stouffer, R. L.. Oregon National Primate Research Center; Estados Unidos. Oregon Health and Science University; Estados Unidos
description STUDY QUESTION Can administration of a prostaglandin (PG) E2 receptor 2 (PTGER2) antagonist prevent pregnancy in adult female monkeys by blocking periovulatory events in the follicle without altering menstrual cyclicity or general health? SUMMARY ANSWER This is the first study to demonstrate that a PTGER2 antagonist can serve as an effective non-hormonal contraceptive in primates. WHAT IS KNOWN ALREADY The requirement for PGE2 in ovulation and the release of an oocyte surrounded by expanded cumulus cells (cumulus–oocyte expansion; C-OE) was established through the generation of PTGS2 and PTGER2 null-mutant mice. A critical role for PGE2 in primate ovulation is supported by evidence that intrafollicular injection of indomethacin in rhesus monkeys suppressed follicle rupture, whereas co-injection of PGE2 with indomethacin resulted in ovulation. STUDY DESIGN, SIZE, DURATION First, controlled ovulation protocols were performed in adult, female rhesus monkeys to analyze the mRNA levels for genes encoding PGE2 synthesis and signaling components in the naturally selected pre-ovulatory follicle at different times after the ovulatory hCG stimulus (0, 12, 24, 36 h pre-ovulation; 36 h post-ovulation, n = 3–4/time point). Second, controlled ovarian stimulation cycles were utilized to obtain multiple cumulus–oocyte complexes (COCs) from rhesus monkeys to evaluate the role of PGE2 in C-OE in vitro (n = 3–4 animals/treatment; ≥3 COCs/animal/treatment). Third, adult cycling female cynomolgus macaques were randomly assigned (n = 10/group) to vehicle (control) or PTGER2 antagonist (BAY06) groups to perform a contraceptive trial. After the first treatment cycle, a male of proven fertility was introduced into each group and they remained housed together for the duration of the 5-month contraceptive trial that was followed by a post-treatment reversibility trial. PARTICIPANTS/MATERIALS, SETTING, METHODS Quantitative real-time PCR, COC culture and expansion, immunofluorescence/confocal microscopy, enzyme immunoassay, contraceptive trial, ultrasonography, complete blood counts, serum biochemistry tests and blood lipid profiles. MAIN RESULTS AND THE ROLE OF CHANCE Several mRNAs encoding proteins involved in PGE2 synthesis, metabolism and signaling increase (P < 0.05) in the periovulatory follicle after administration of an ovulatory hCG bolus. PGE2 signaling through PTGER2 induces cumulus cell expansion and production of hyaluronic acid, which are critical events for fertilization. Moreover, chronic administration of a selective PTGER2 antagonist resulted in a significant (P < 0.05 versus vehicle-treated controls) contraceptive effect without altering steroid hormone patterns or menstrual cyclicity during a 5-months contraceptive trial. Fertility recovered as early as 1 month after ending treatment. LIMITATIONS, REASONS FOR CAUTION This is a proof-of-concept study in a non-human primate model. Further investigations are warranted to elucidate the mechanism(s) of PTGER2 antagonist action in the primate ovary. Although PTGER2 antagonist treatment did not produce any obvious undesirable effects, improvements in the mode of administration, as well as the efficacy of these compounds, are necessary to consider such a contraceptive for women. WIDER IMPLICATIONS OF THE FINDINGS Monitoring as well as improving the efficacy and safety of female contraceptives is an important public health activity. Even though hormonal contraceptives are effective for women, concerns remain regarding their side-effects and long-term use because of the widespread actions of such steroidal products in many tissues. Moreover, some women cannot take hormones for medical reasons. Thus, development of non-hormonal contraceptives for women is warranted. STUDY FUNDING/COMPETING INTEREST(S) Supported by Bayer HealthCare Pharmaceuticals, The Eunice Kennedy Shriver NICHD Contraceptive Development and Research Center (U54 HD055744), NIH Office of the Director (Oregon National Primate Research Center P51 OD011092), and a Lalor Foundation Postdoctoral Basic Research Fellowship (MCP). The use of the Leica confocal was supported by grant number S10RR024585. Some of the authors (N.B., A.R., K.-H.F., U.F., B.B. and B.L.) are employees of Bayer Healthcare Pharma.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/8189
Peluffo, Marina Cinthia; Stanley, J.; Braeuer, N.; Rotgeri, A.; Fritzemeier, K. H.; et al.; A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques; Oxford University Press; Human Reproduction; 29; 7; 3-2014; 1400-1412
0268-1161
url http://hdl.handle.net/11336/8189
identifier_str_mv Peluffo, Marina Cinthia; Stanley, J.; Braeuer, N.; Rotgeri, A.; Fritzemeier, K. H.; et al.; A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques; Oxford University Press; Human Reproduction; 29; 7; 3-2014; 1400-1412
0268-1161
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://humrep.oxfordjournals.org/content/29/7/1400.long
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059334/
info:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/deu083
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613472761937920
score 13.070432