The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows

Aim OvSynch is a hormonal protocol for synchronization of estrus and use of artificial insemination (AI) at an optimal time without adverse effects on the ovaries or uterus. This study investigated the use of noninvasive color Doppler ultrasound to assess changes in uterine and vaginal blood flow du...

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Autores:
Sharawy, Heba A.
Hegab, AbdelRaouf O.
Engy F., Risha
Mohamed, El‑Adl
Fahmy, Reham A.
Farag, Virginia M.
Gohar, Mohamed A.
Soliman, Walid T.
Imakawa, Kazuhiko
Bazer, Fuller W.
James, Daniela
Zaghloul, Adel
Tipo de recurso:
Article of investigation
Fecha de publicación:
2022
Institución:
Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
Repositorio:
Repositorio Institucional UDCA
Idioma:
eng
OAI Identifier:
oai:repository.udca.edu.co:11158/5023
Acceso en línea:
https://repository.udca.edu.co/handle/11158/5023
https://doi.org/10.1186/s12917-022-03444-9
Palabra clave:
Hidrocortisona
Cloprostenol
Bovinos
Dinoprost
Estrógenos
Sincronización del Estro
Hormona Liberadora de Gonadotropina
Embarazo
Flujo sanguíneo uterino
Rights
openAccess
License
https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.es
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oai_identifier_str oai:repository.udca.edu.co:11158/5023
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network_name_str Repositorio Institucional UDCA
repository_id_str
dc.title.eng.fl_str_mv The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
title The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
spellingShingle The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
Hidrocortisona
Cloprostenol
Bovinos
Dinoprost
Estrógenos
Sincronización del Estro
Hormona Liberadora de Gonadotropina
Embarazo
Flujo sanguíneo uterino
title_short The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
title_full The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
title_fullStr The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
title_full_unstemmed The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
title_sort The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows
dc.creator.fl_str_mv Sharawy, Heba A.
Hegab, AbdelRaouf O.
Engy F., Risha
Mohamed, El‑Adl
Fahmy, Reham A.
Farag, Virginia M.
Gohar, Mohamed A.
Soliman, Walid T.
Imakawa, Kazuhiko
Bazer, Fuller W.
James, Daniela
Zaghloul, Adel
dc.contributor.author.none.fl_str_mv Sharawy, Heba A.
Hegab, AbdelRaouf O.
Engy F., Risha
Mohamed, El‑Adl
Fahmy, Reham A.
Farag, Virginia M.
Gohar, Mohamed A.
Soliman, Walid T.
Imakawa, Kazuhiko
Bazer, Fuller W.
James, Daniela
Zaghloul, Adel
dc.subject.armarc.none.fl_str_mv Hidrocortisona
topic Hidrocortisona
Cloprostenol
Bovinos
Dinoprost
Estrógenos
Sincronización del Estro
Hormona Liberadora de Gonadotropina
Embarazo
Flujo sanguíneo uterino
dc.subject.decs.none.fl_str_mv Cloprostenol
Bovinos
Dinoprost
Estrógenos
Sincronización del Estro
Hormona Liberadora de Gonadotropina
Embarazo
dc.subject.proposal.spa.fl_str_mv Flujo sanguíneo uterino
description Aim OvSynch is a hormonal protocol for synchronization of estrus and use of artificial insemination (AI) at an optimal time without adverse effects on the ovaries or uterus. This study investigated the use of noninvasive color Doppler ultrasound to assess changes in uterine and vaginal blood flow during the Ovsynch program for synchronization of estrus and its relation to the pregnancy rates in Holstein cows. Materials and methods The experimental cows received an intramuscular dose of 10 μg of a GnRH analogue (G1), followed 7 days later with an intramuscular injection of synthetic prostaglandin F2α (P: PGF2α) analogue (500 μg cloprostenol sodium), and given a 10 μg, injection of the GnRH analogue (G2) i.m. 48 h after the PGF2α treatment, and the cows were bred 14-16 h after. Uterine and vaginal perfusion were investigated by performing transrectal Doppler ultrasonography of both the uterine and vaginal arteries in Holstein cows at different time points during the Ovsynch program to determine: peak systolic velocity (PSV), time-averaged maximum velocity (TAMV), the volume of blood flow (BFV), pulsatility index (PI), resistance index (RI), resistance impedance (S/D) and diameters of uterine (UA) and vaginal (VA) arteries. Steroid hormones were also assayed. Transrectal ultrasonography (TUS) was performed at 32 and 60 days to confirm the pregnancy per artificial insemination (P/AI). Results The uterine PSV, TAMV, and PV were greater at the time of the cloprostenol sodium and second GnRH injections (p<0.05) than at the time of the first GnRH injection. The vaginal PSV, PV were greater at the time of the cloprostenol sodium than at the time of the first and second GnRH injections (p<0.05). The receiver operating characteristic curve (ROC curve) indicated a high correlation between the uterine and vaginal blood flow and the rate of the pregnancy (p<0.05). The area under the ROC curve was 0.920 and 0.87 (p<0.05) for vaginal and uterine arteries respectively at time of G2. The serum levels of progesterone, estrogen and cortisol were correlated with the P/AI (p<0.05). The P/AI significantly decreased from 43.9 % at 32 d to 35.37 % at 60 d. Conclusion These results indicate that noninvasive Doppler ultrasonography is a valid method to evaluate changes in the characteristics of uterine and vaginal blood flow in cows during the Ovsynch protocol. Furthermore, vaginal and uterine blood flow are two determinant factors for the higher conception rates in Holstein dairy cows.
publishDate 2022
dc.date.issued.none.fl_str_mv 2022
dc.date.accessioned.none.fl_str_mv 2023-01-23T21:46:24Z
dc.date.available.none.fl_str_mv 2023-01-23T21:46:24Z
dc.type.spa.fl_str_mv Artículo de revista
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dc.identifier.citation.spa.fl_str_mv Sharawy, H.A., Hegab, A.O., Risha, E.F. et al. The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows. BMC Vet Res 18, 350 (2022). https://doi.org/10.1186/s12917-022-03444-9
dc.identifier.issn.spa.fl_str_mv 1746-6148
dc.identifier.uri.none.fl_str_mv https://repository.udca.edu.co/handle/11158/5023
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1186/s12917-022-03444-9
identifier_str_mv Sharawy, H.A., Hegab, A.O., Risha, E.F. et al. The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows. BMC Vet Res 18, 350 (2022). https://doi.org/10.1186/s12917-022-03444-9
1746-6148
url https://repository.udca.edu.co/handle/11158/5023
https://doi.org/10.1186/s12917-022-03444-9
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.indexed.spa.fl_str_mv Agrosavia
dc.relation.citationedition.spa.fl_str_mv (Dic., 2022) Artículo número 350
dc.relation.citationendpage.spa.fl_str_mv 13
dc.relation.citationissue.spa.fl_str_mv 1
dc.relation.citationstartpage.spa.fl_str_mv 1
dc.relation.citationvolume.spa.fl_str_mv 18
dc.relation.ispartofjournal.spa.fl_str_mv BMC Veterinary Research
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spelling Sharawy, Heba A.Hegab, AbdelRaouf O.Engy F., RishaMohamed, El‑AdlFahmy, Reham A.Farag, Virginia M.Gohar, Mohamed A.Soliman, Walid T.Imakawa, KazuhikoBazer, Fuller W.James, DanielaZaghloul, Adel2023-01-23T21:46:24Z2023-01-23T21:46:24Z2022Sharawy, H.A., Hegab, A.O., Risha, E.F. et al. The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows. BMC Vet Res 18, 350 (2022). https://doi.org/10.1186/s12917-022-03444-91746-6148https://repository.udca.edu.co/handle/11158/5023https://doi.org/10.1186/s12917-022-03444-9Aim OvSynch is a hormonal protocol for synchronization of estrus and use of artificial insemination (AI) at an optimal time without adverse effects on the ovaries or uterus. This study investigated the use of noninvasive color Doppler ultrasound to assess changes in uterine and vaginal blood flow during the Ovsynch program for synchronization of estrus and its relation to the pregnancy rates in Holstein cows. Materials and methods The experimental cows received an intramuscular dose of 10 μg of a GnRH analogue (G1), followed 7 days later with an intramuscular injection of synthetic prostaglandin F2α (P: PGF2α) analogue (500 μg cloprostenol sodium), and given a 10 μg, injection of the GnRH analogue (G2) i.m. 48 h after the PGF2α treatment, and the cows were bred 14-16 h after. Uterine and vaginal perfusion were investigated by performing transrectal Doppler ultrasonography of both the uterine and vaginal arteries in Holstein cows at different time points during the Ovsynch program to determine: peak systolic velocity (PSV), time-averaged maximum velocity (TAMV), the volume of blood flow (BFV), pulsatility index (PI), resistance index (RI), resistance impedance (S/D) and diameters of uterine (UA) and vaginal (VA) arteries. Steroid hormones were also assayed. Transrectal ultrasonography (TUS) was performed at 32 and 60 days to confirm the pregnancy per artificial insemination (P/AI). Results The uterine PSV, TAMV, and PV were greater at the time of the cloprostenol sodium and second GnRH injections (p<0.05) than at the time of the first GnRH injection. The vaginal PSV, PV were greater at the time of the cloprostenol sodium than at the time of the first and second GnRH injections (p<0.05). The receiver operating characteristic curve (ROC curve) indicated a high correlation between the uterine and vaginal blood flow and the rate of the pregnancy (p<0.05). The area under the ROC curve was 0.920 and 0.87 (p<0.05) for vaginal and uterine arteries respectively at time of G2. The serum levels of progesterone, estrogen and cortisol were correlated with the P/AI (p<0.05). The P/AI significantly decreased from 43.9 % at 32 d to 35.37 % at 60 d. Conclusion These results indicate that noninvasive Doppler ultrasonography is a valid method to evaluate changes in the characteristics of uterine and vaginal blood flow in cows during the Ovsynch protocol. Furthermore, vaginal and uterine blood flow are two determinant factors for the higher conception rates in Holstein dairy cows.Incluye referencias bibliográficasapplication/pdfenghttps://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.eshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-022-03444-9The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cowsArtículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/coar/version/c_970fb48d4fbd8a85HidrocortisonaCloprostenolBovinosDinoprostEstrógenosSincronización del EstroHormona Liberadora de GonadotropinaEmbarazoFlujo sanguíneo uterinoAgrosavia(Dic., 2022) Artículo número 350131118BMC Veterinary ResearchPublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-814775https://repository.udca.edu.co/bitstreams/a59af390-02bd-4321-9d32-3d9c72adfcf1/downloadf661acf14bedbf9f5d13897a0387e751MD52ORIGINALs12917-022-03444-9.pdfs12917-022-03444-9.pdfapplication/pdf2943398https://repository.udca.edu.co/bitstreams/da6f10af-cf2f-42c2-afa7-e34a5162d1d7/download2782621f19b4c26a847935b05423de0aMD51TEXTs12917-022-03444-9.pdf.txts12917-022-03444-9.pdf.txtExtracted texttext/plain53746https://repository.udca.edu.co/bitstreams/048414e0-2056-471f-8f06-47e743d7b85d/downloada7cf58d6fb11d1fb29ff524b489c0a04MD53THUMBNAILs12917-022-03444-9.pdf.jpgs12917-022-03444-9.pdf.jpgGenerated Thumbnailimage/jpeg14616https://repository.udca.edu.co/bitstreams/7ec5d82a-0cd7-467e-99be-f12d858c8698/downloadbdd4c77a81892847e411853b23aa8cddMD5411158/5023oai:repository.udca.edu.co:11158/50232024-05-09 14:34:39.937https://creativecommons.org/licenses/by-nc-sa/4.0/https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.esopen.accesshttps://repository.udca.edu.coRepositorio - Universidad de Ciencias Aplicadas y Ambientales 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 nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.
d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.
ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.
e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, Acinpro), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.
5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
7. Término.
a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.
b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.
8. Varios.
a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.
b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.
c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.
d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.

