Prenatal androgenization: its impact on offspring´s development and reproductive phenotype
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. Among others, this disorder is characterized by reproductive disorders and even, subfertility. Animal models of PCOS use androgen administration protocols in critical periods (usually prenatal), since...
| Autores principales: | , , , |
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| Formato: | Artículo revista |
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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/39072 |
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I10-R327-article-39072 |
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ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
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R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
prenatal androgenization posnatal development reproductive phenotype dihydrotestosterone polycystic ovary syndrome androgenización prenatal desarrollo posnatal fenotipo reproductivo dihidrotestosterona síndrome de ovario poliquístico |
| spellingShingle |
prenatal androgenization posnatal development reproductive phenotype dihydrotestosterone polycystic ovary syndrome androgenización prenatal desarrollo posnatal fenotipo reproductivo dihidrotestosterona síndrome de ovario poliquístico Torres, PJ Ramírez, ND Luque, EM Martini, AC Prenatal androgenization: its impact on offspring´s development and reproductive phenotype |
| topic_facet |
prenatal androgenization posnatal development reproductive phenotype dihydrotestosterone polycystic ovary syndrome androgenización prenatal desarrollo posnatal fenotipo reproductivo dihidrotestosterona síndrome de ovario poliquístico |
| author |
Torres, PJ Ramírez, ND Luque, EM Martini, AC |
| author_facet |
Torres, PJ Ramírez, ND Luque, EM Martini, AC |
| author_sort |
Torres, PJ |
| title |
Prenatal androgenization: its impact on offspring´s development and reproductive phenotype |
| title_short |
Prenatal androgenization: its impact on offspring´s development and reproductive phenotype |
| title_full |
Prenatal androgenization: its impact on offspring´s development and reproductive phenotype |
| title_fullStr |
Prenatal androgenization: its impact on offspring´s development and reproductive phenotype |
| title_full_unstemmed |
Prenatal androgenization: its impact on offspring´s development and reproductive phenotype |
| title_sort |
prenatal androgenization: its impact on offspring´s development and reproductive phenotype |
| description |
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. Among others, this disorder is characterized by reproductive disorders and even, subfertility. Animal models of PCOS use androgen administration protocols in critical periods (usually prenatal), since maternal exposure to androgens is postulated as the main causal factor. In this randomized controlled study, we tested whether androgenization of pregnant female mice (F0) elicits a PCOS-like phenotype in F1 offspring.
We treated female Albino Swiss (N/NIH) mice (F0; n=5-6 females/treatment) s.c. during gestational days 16.5 to 18.5, with 250 µg/day of dihydrotestosterone (DHT), vehiculized in 100 µl of sesame oil. Control females (C) received vehicle at the same regimen. Parameters evaluated in F1 were: growth and physical development, sexual maturation and, in adulthood, reproductive function. Data were analyzed using ANOVA or repeated measures ANOVA as appropriate.
The female offspring of the DHT group gained more weight from birth to adulthood than C group (DHT=23.38±0.40 vs C=21.7±0.5; n=5 litters/group; p<0.05); a very similar profile was seen in the male pups, although differences were not significant. Both female and male DHT pups exhibited advanced puberty onset (vaginal opening: on postnatal days 29, 30, and 33; p<0.05 vs C; testicular descent: on postnatal day 21 vs C; p<0.05). Anogenital distance was higher in the adult female offspring from the DHT group (DHT=7.62±0.08 vs C=7.30±0.11; n=20-25 animals/group; p<0.05). Regarding sperm functional activity, the adult male offspring of the DHT group showed lower percentages of motile spermatozoa (DHT=55.44±3.12 vs C=64.18±2.69; n=17-18 males/group ; p<0.05) and lower percentages of sperm viability (DHT=92.25±0.55 vs C=94.27±0.71; n=11-12 males/group; p<0.05). The reproductive function of the female pups did not change.
In conclusion, prenatal androgenization exerts programming effects that include modifications in growth, sexual maturation, and sperm function in adult males. This phenotype is similar to that of PCOS. |
| 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/39072 |
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I10-R327-article-390722024-04-15T16:14:45Z Prenatal androgenization: its impact on offspring´s development and reproductive phenotype Impacto de la androgenización prenatal en el desarrollo posnatal y el fenotipo reproductivo de la descendencia Torres, PJ Ramírez, ND Luque, EM Martini, AC prenatal androgenization posnatal development reproductive phenotype dihydrotestosterone polycystic ovary syndrome androgenización prenatal desarrollo posnatal fenotipo reproductivo dihidrotestosterona síndrome de ovario poliquístico Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. Among others, this disorder is characterized by reproductive disorders and even, subfertility. Animal models of PCOS use androgen administration protocols in critical periods (usually prenatal), since maternal exposure to androgens is postulated as the main causal factor. In this randomized controlled study, we tested whether androgenization of pregnant female mice (F0) elicits a PCOS-like phenotype in F1 offspring. We treated female Albino Swiss (N/NIH) mice (F0; n=5-6 females/treatment) s.c. during gestational days 16.5 to 18.5, with 250 µg/day of dihydrotestosterone (DHT), vehiculized in 100 µl of sesame oil. Control females (C) received vehicle at the same regimen. Parameters evaluated in F1 were: growth and physical development, sexual maturation and, in adulthood, reproductive function. Data were analyzed using ANOVA or repeated measures ANOVA as appropriate. The female offspring of the DHT group gained more weight from birth to adulthood than C group (DHT=23.38±0.40 vs C=21.7±0.5; n=5 litters/group; p<0.05); a very similar profile was seen in the male pups, although differences were not significant. Both female and male DHT pups exhibited advanced puberty onset (vaginal opening: on postnatal days 29, 30, and 33; p<0.05 vs C; testicular descent: on postnatal day 21 vs C; p<0.05). Anogenital distance was higher in the adult female offspring from the DHT group (DHT=7.62±0.08 vs C=7.30±0.11; n=20-25 animals/group; p<0.05). Regarding sperm functional activity, the adult male offspring of the DHT group showed lower percentages of motile spermatozoa (DHT=55.44±3.12 vs C=64.18±2.69; n=17-18 males/group ; p<0.05) and lower percentages of sperm viability (DHT=92.25±0.55 vs C=94.27±0.71; n=11-12 males/group; p<0.05). The reproductive function of the female pups did not change. In conclusion, prenatal androgenization exerts programming effects that include modifications in growth, sexual maturation, and sperm function in adult males. This phenotype is similar to that of PCOS. El síndrome de ovario poliquístico (SOP) es la endocrinopatía más frecuente entre las mujeres en edad reproductiva. Se caracteriza, entre otros, por provocar alteraciones reproductivas e incluso subfertilidad. Los modelos animales de SOP utilizan protocolos de administración de andrógenos en períodos críticos (en general, prenatal), ya que se postula a la exposición materna a andrógenos como el factor causal. En este estudio randomizado controlado, analizamos si la androgenización de ratones hembras preñadas (F0) provoca en la descendencia F1, un fenotipo tipo SOP. Tratamos durante los días gestacionales 16,5 a 18,5 a hembras de ratón Albino swiss (N/NIH) (F0; n=5-6 hembras/tratamiento) s.c. con 250 µg/día de dihidrotestosterona (DHT), vehiculizada en 100 µl de aceite de sésamo. Las hembras controles (C) recibieron el vehículo en el mismo régimen. Los parámetros evaluados en la F1 fueron: crecimiento y desarrollo físico, maduración sexual y, en la adultez, función reproductiva. Los datos se analizaron mediante ANAVA clásico o de medidas repetidas según corresponda. Las crías hembras del grupo DHT ganaron más peso que las C (DHT=23,38±0,40 vs C=21,7±0,5; n=5 camadas/grupo; p<0,05) y, aunque no se observaron diferencias significativas en las crías machos, el perfil fue muy similar. Tanto los crías hembras como las machos de DHT adelantaron el desarrollo puberal (apertura vaginal: en días-posnatales 29, 30 y 33; p<0,05 vs C; descenso testicular: en día-posnatal 21 vs C; p<0,05). La distancia anogenital fue mayor en las crías hembras adultas del grupo DHT (DHT=7,62±0,08 vs C=7,30±0,11; n=20-25 animales/grupo; p<0,05). En cuanto a la actividad funcional espermática, las crías macho adultas del grupo DHT presentaron menor porcentaje de espermatozoides móviles (DHT=55,44±3,12 vs C=64,18±2,69; n=17-18 machos/grupo; p<0,05) y menor vitalidad espermática (DHT=92,25±0,55 vs C=94,27±0,71; n=11-12 machos/grupo; p<0,05). La función reproductiva de las crías hembras no sufrió modificaciones. En conclusión, la androgenización prenatal ejerce efectos programadores que incluyen modificaciones en el crecimiento, en la maduración sexual y en la función espermática de los machos adultos. El fenotipo en las hembras es similar al de SOP, y el de los machos, ha sido descripto en otros trabajos de investigación básica. 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/39072 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 Derechos de autor 2022 Universidad Nacional de Córdoba http://creativecommons.org/licenses/by-nc/4.0 |