Effects of ovarian hyperstimulation on early embryo development: a study in a murine model

Controlled ovarian hyperstimulation (COH) is a protocol commonly applied in assisted reproduction techniques. It involves the pharmacological stimulation of the ovaries, in order to increase the number of oocytes recovered and fertilization probabilities. However, the concomitant increase in se...

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Autores principales: Ramírez, ND, Torres, PJ, Luque, E, Ponzio, M, Cantarelli, V, Motrich, R, Martini, AC
Formato: Artículo revista
Publicado: Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022
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Acceso en línea:https://revistas.unc.edu.ar/index.php/med/article/view/39077
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record_format ojs
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-327
container_title_str Revista de la Facultad de Ciencias Médicas de Córdoba
format Artículo revista
topic controlled ovarian hyperstimulation
embryo development
oocytes quality
morula
blastocyst
hiperestimulación ovárica controlada
desarrollo embrionario
calidad ovocitaria
mórula
blastocisto
spellingShingle controlled ovarian hyperstimulation
embryo development
oocytes quality
morula
blastocyst
hiperestimulación ovárica controlada
desarrollo embrionario
calidad ovocitaria
mórula
blastocisto
Ramírez, ND
Torres, PJ
Luque, E
Ponzio, M
Cantarelli, V
Motrich, R
Martini, AC
Effects of ovarian hyperstimulation on early embryo development: a study in a murine model
topic_facet controlled ovarian hyperstimulation
embryo development
oocytes quality
morula
blastocyst
hiperestimulación ovárica controlada
desarrollo embrionario
calidad ovocitaria
mórula
blastocisto
author Ramírez, ND
Torres, PJ
Luque, E
Ponzio, M
Cantarelli, V
Motrich, R
Martini, AC
author_facet Ramírez, ND
Torres, PJ
Luque, E
Ponzio, M
Cantarelli, V
Motrich, R
Martini, AC
author_sort Ramírez, ND
title Effects of ovarian hyperstimulation on early embryo development: a study in a murine model
title_short Effects of ovarian hyperstimulation on early embryo development: a study in a murine model
title_full Effects of ovarian hyperstimulation on early embryo development: a study in a murine model
title_fullStr Effects of ovarian hyperstimulation on early embryo development: a study in a murine model
title_full_unstemmed Effects of ovarian hyperstimulation on early embryo development: a study in a murine model
title_sort effects of ovarian hyperstimulation on early embryo development: a study in a murine model
description Controlled ovarian hyperstimulation (COH) is a protocol commonly applied in assisted reproduction techniques. It involves the pharmacological stimulation of the ovaries, in order to increase the number of oocytes recovered and fertilization probabilities. However, the concomitant increase in sexual steroid levels are thought to negatively impact on embryo development. The aim of this study was to assess the possible impact of COH on ovulation, fertilization and preimplantation embryo development in a mouse model. Albino Swiss (N:NIH) adult female mice were treated (COH group) with human menopausic gonadotropin and human chorionic gonadotropin (10 I.U/day each), and oocytes number and quality were recorded. A second COH group was mated with untreated males, and their uteri were removed (three days post coitus), in order to asses embryos/oocytes number and developmental stage (2-8 cells, early/late morula and compact/expanded blastocyst). The percentage of fertilization was calculated considering embryo and corpora lutea numbers. Females in natural estrous were used as the control group (C). Results were analyzed by T/Mann-Whitney test; in all cases p<0.05 was considered significant. Ovulation rate was higher in COH vs. C (27.82±2.92 vs 10.15±0.71, n=17-13; p<0.05), but no differences were found in oocytes quality. The COH increased plasmatic progesterone (6.16±1.05ng/ml vs 0.78±0.29ng/ml; n=6-5; p<0.05), but not the estradiol levels. Although there were no significant differences in the percentage of fertilized oocytes, the COH group showed a delayed embryo development, evidenced by an increased in late morulas (78.83% vs 40.28%; n=11-9; p<0.05) and a decrease in blastocysts (15.25% vs 55.55%; n=11-9; p<0.05). The supraphysiological levels of sexual hormones are a possible explanation for these effects, since sexual steroids could modify the epithelial-secreted cytokines profile, that are well known as embryo development modulators. We are currently performing studies in this regard. In summary, COH did not affect oocyte quality, but delayed early embryo development. These results are of potential clinical relevance.
publisher Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
publishDate 2022
url https://revistas.unc.edu.ar/index.php/med/article/view/39077
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spelling I10-R327-article-390772024-04-15T16:14:45Z Effects of ovarian hyperstimulation on early embryo development: a study in a murine model Efectos de la hiperestimulación ovárica controlada en el desarrollo embrionario temprano: estudio en un modelo murino Ramírez, ND Torres, PJ Luque, E Ponzio, M Cantarelli, V Motrich, R Martini, AC controlled ovarian hyperstimulation embryo development oocytes quality morula blastocyst hiperestimulación ovárica controlada desarrollo embrionario calidad ovocitaria mórula blastocisto Controlled ovarian hyperstimulation (COH) is a protocol commonly applied in assisted reproduction techniques. It involves the pharmacological stimulation of the ovaries, in order to increase the number of oocytes recovered and fertilization probabilities. However, the concomitant increase in sexual steroid levels are thought to negatively impact on embryo development. The aim of this study was to assess the possible impact of COH on ovulation, fertilization and preimplantation embryo development in a mouse model. Albino Swiss (N:NIH) adult female mice were treated (COH group) with human menopausic gonadotropin and human chorionic gonadotropin (10 I.U/day each), and oocytes number and quality were recorded. A second COH group was mated with untreated males, and their uteri were removed (three days post coitus), in order to asses embryos/oocytes number and developmental stage (2-8 cells, early/late morula and compact/expanded blastocyst). The percentage of fertilization was calculated considering embryo and corpora lutea numbers. Females in natural estrous were used as the control group (C). Results were analyzed by T/Mann-Whitney test; in all cases p<0.05 was considered significant. Ovulation rate was higher in COH vs. C (27.82±2.92 vs 10.15±0.71, n=17-13; p<0.05), but no differences were found in oocytes quality. The COH increased plasmatic progesterone (6.16±1.05ng/ml vs 0.78±0.29ng/ml; n=6-5; p<0.05), but not the estradiol levels. Although there were no significant differences in the percentage of fertilized oocytes, the COH group showed a delayed embryo development, evidenced by an increased in late morulas (78.83% vs 40.28%; n=11-9; p<0.05) and a decrease in blastocysts (15.25% vs 55.55%; n=11-9; p<0.05). The supraphysiological levels of sexual hormones are a possible explanation for these effects, since sexual steroids could modify the epithelial-secreted cytokines profile, that are well known as embryo development modulators. We are currently performing studies in this regard. In summary, COH did not affect oocyte quality, but delayed early embryo development. These results are of potential clinical relevance. La hiperestimulación ovárica controlada (HOC), parte integral de las técnicas de reproducción asistida, consiste en la estimulación farmacológica gonadal para obtener más ovocitos y aumentar las chances de fertilización. Paralelamente, induce un aumento suprafisiológico de esteroides sexuales, que podría impactar sobre el desarrollo embrionario. El objetivo de este estudio fue analizar el efecto de la HOC sobre la ovulación, la fertilización y el desarrollo embrionario preimplantatorio, utilizando un modelo murino. Ratones hembras adultas Albino Swiss (N:NIH) fueron inducidas a superovular (grupo HOC), con 10UI de gonadotrofina menopáusica humana y 10UI de gonadotropina coriónica humana y, tras punción de la ampolla, se evaluó cantidad y calidad ovocitaria. Otro grupo de hembras HOC se apareó con machos sin tratamiento y, tres días después de verificar la cópula, se les extirparon los úteros. Tras el lavado de ambos cuernos con Tyrode, se contabilizó cantidad de ovocitos/embriones y grado de desarrollo de los mismos (2-8 células, mórulas tempranas/tardías y blastocitos compactos/expandidos). En base al recuento de cuerpos lúteos, se evaluó el porcentaje de fertilización. Hembras en ciclo natural (CN) se utilizaron como grupo control. Los resultados fueron analizados mediante test T/Mann-Whitney y 5% de nivel de significancia. Las hembras HOC presentaron una tasa de ovulación mayor a las hembras en CN (27,82±2,92 vs 10,15±0,71, n=17-13; p<0,05), sin variaciones en la calidad ovocitaria. La HOC también aumentó la progesterona plasmática (6,16±1,05ng/ml vs 0,78±0,29ng/ml; n=6-5; p<0,05), aunque no el estradiol. Si bien no hubo diferencias significativas en el porcentaje de ovocitos fertilizados, se evidenció en HOC un retraso en el desarrollo embrionario, reflejado en un aumento en la proporción de mórulas (78.83% vs 40.28%; n=11-9; p<0,05), particularmente las tardías, y una disminución en la de blastocitos (15.25% vs 55.55%; n=11-9; p<0,05). Estos resultados podrían atribuirse a los niveles suprafisiológicos de hormonas sexuales, que modificarían el perfil de citoquinas liberadas por el epitelio oviductal, que normalmente modulan el desarrollo embrionario temprano. Actualmente se están realizando experimentos a este respecto. En conclusión, la HOC no afectó la calidad de las gametas, pero retrasó el desarrollo embrionario preimplantatorio. Estos resultados tienen una interesante proyección clínica. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022-10-26 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto https://revistas.unc.edu.ar/index.php/med/article/view/39077 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 79 No. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 79 Núm. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista da Faculdade de Ciências Médicas de Córdoba; v. 79 n. Suplemento JIC XXIII (2022): Suplemento JIC XXIII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0