Investigadores de la Clínica de Mujeres Kato de Tokio (Japón) han descubierto que, cuando se trasplantan ovarios de ratones hembra jóvenes a ratones de edad avanzada, el procedimiento no sólo devuelve a las últimas la fertilidad, sino que rejuvenece su comportamiento y prolonga su vida. El descubrimiento se anuncia este martes en la 26 Conferencia Anual de la Sociedad Europea de Reproducción Humana y Embriología (ESHRE, por sus siglas en inglés, que se celebra en Roma.
Según la doctora Noriko Kagawa, directora Asociada de Investigación de la Clínica de Mujeres Kato de Tokio (Japón), "en la actualidad, los trasplantes de ovarios se llevan a cabo con el objeto de preservar la fertilidad de las mujeres tras un tratamiento contra el cáncer o para prolongar su etapa reproductiva".
"Sin embargo, el beneficio adicional, totalmente inesperado, de los procedimientos de preservación de la fertilidad en nuestros estudios con ratones indica que existe la posibilidad de que la aplicación de procedimientos similares en mujeres pueda prolongar su vida en general", señala.
El número de trasplantes de ovarios en mujeres realizados en el mundo es muy reducido y han tenido un éxito dispar. La doctora Kagawa subraya que todavía queda mucho por investigar antes de que se pueda saber si los trasplantes de ovarios producen efectos rejuvenecedores similares en las mujeres, sobre todo porque supone esperar muchos años a que las pacientes envejezcan.
Los autores de este trabajo desarrollaron dos experimentos con ratones. En el primero, se extirparon los dos ovarios a ratones hembra jóvenes --de unos 140 días de edad-- y se trasplantaron en seis ratones hembra mucho mayores --de más de 525 días de edad--, que ya eran demasiado viejas para ser fértiles.
En el segundo experimento se extirpó un solo ovario a los ratones hembra jóvenes --de unos 170 días de edad-- y se trasplantó en ocho ratones hembra mayores, de más de 540 días de edad).
El ciclo de vida medio normal de esa raza de ratones (C57BL/6J) es de 548 días, y normalmente llegan a la "menopausia" murina en torno a la edad de 525 días.
Todos los ratones hembra que recibieron trasplantes en ambos experimentos recuperaron la fertilidad, a diferencia de los ratones hembra de control, que no recibieron trasplantes.
En el primer experimento, los ratones hembra reanudaron ciclos reproductivos normales que duraron más de 80 días y en el segundo experimento, dichos ciclos duraron más de 130 días.
-EL COMPORTAMIENTO REPRODUCTIVO DE LOS JÓVENES
Según la doctora Kagawa, "todos los ratones hembra de ambos experimentos que recibieron trasplantes reanudaron el comportamiento reproductivo normal de los ratones jóvenes". "Mostraron interés hacia los machos, se aparearon y algunos tuvieron crías", asegura.
Normalmente, los ratones hembra viejos se quedan en un rincón de la jaula y muestran poco movimiento, pero la actividad de los ratones hembra que recibieron trasplantes de ovarios se equiparó a la de los ratones jóvenes, reemprendiendo los movimientos rápidos.
Además, la vida de los ratones hembra que recibieron ovarios jóvenes fue mucho más larga que la de los ratones hembra de control: los ratones que recibieron dos ovarios vivieron un promedio de 915 días y los ratones que recibieron un ovario, un promedio de 877 días. Los datos mas recientes indican que la vida de los ratones hembra que recibieron trasplantes de ovarios jóvenes se prolongó en más de un 40 por ciento.
"Los resultados demuestran que los ovarios normales de ratones hembra jóvenes trasplantados en ratones hembra de edad avanzada y estériles pueden funcionar y devolverles la fertilidad y que, además, les prolongan la vida", indica.
"A las mujeres que congelan tejido ovárico de jóvenes, quizás porque están a punto de iniciar un tratamiento contra el cáncer, se les puede volver a trasplantar su tejido ovárico joven cuando sean mayores. Normalmente, lo haríamos sólo para preservar su fertilidad o para prolongar su etapa reproductiva", afirma.
"Sin embargo, nuestro experimento con ratones sugiere que este procedimiento también puede mejorar la longevidad general. Hay que seguir investigando para saber si realmente es así", asevera.
Showing posts with label estimulación hormonal en ovarios. Show all posts
Showing posts with label estimulación hormonal en ovarios. Show all posts
29 June 2010
Researchers discover why some women are sub-fertile and have a poor response to ovarian stimulating hormones
Researchers have discovered that some women carry a genetic variation that makes them sub-fertile and less likely to respond to ovarian stimulating hormones during fertility treatment. The discovery opens the way to identifying these women and devising personalised fertility treatments that could bypass the problem caused by the genetic abnormality.
Dr Maria Lalioti told the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome today (Tuesday) that she and her colleagues from the Yale University Medical School, New Haven (USA), had found that some women had an abnormal hormone receptor on cells surrounding oocytes (eggs). This abnormal receptor impaired the function of normal receptors that were also present and resulted in the affected women responding less well to Follicle Stimulating Hormone (FSH), which is given to women during fertility treatment to stimulate the production of more than one oocyte.
Dr Lalioti, as assistant professor in the Department of Obstetrics Gynecology and Reproductive Sciences at Yale, said: "When a woman undergoes in vitro fertilisation, she receives medication called Follicle Stimulating Hormone to produce more than one oocyte, which is the normal production each month. Cells called granulosa cells, which surround the oocyte, receive the FSH; these cells excrete other factors that ‘feed’ the oocyte. The granulosa cells have proteins present on their surface called FSH receptors (or FSHR) and it is these proteins that stick to the FSH and then carry signals into the cell’s interior. When we looked at a portion of these granulosa cells in the laboratory we saw that in some women, who produced very few oocytes, there were some receptors that lacked a piece of the protein, although there were still other, normal FSHR in the women’s cells."
The abnormal FSHR contained a deleted sequence of protein called exon 2 that is an important part of the protein that binds the FSH; FSHR with the exon 2 deletion was only detected in women younger than 35 who had a poor response to FSH and yielded less than four oocytes in a follicle stimulating cycle.
"We produced the normal and abnormal protein in the lab in a different type of cell called HEK293 (Human Embryonic Kidney) which is a common cell type used in the labs to examine properties of proteins. We saw that when the abnormal receptor was present, the normal one could no longer work as well as it does when it is the only protein present," explained Dr Lalioti. "The receptor is normally present on the cell surface in order to meet and bind FSH, and it needs to go through a number of cellular checkpoints inside the cell that assure the quality of the protein presented on the surface. We saw that the abnormal receptor remains longer in one of these checkpoint compartments, indicating that the cell has detected a problem and is trying to correct it. In this way the abnormal FSHR can contribute to an abnormally low response to stimulation in certain women undergoing IVF."
Dr Lalioti’s discovery of the mechanism behind why some young women have a poor response to FSH has important implications for future research and treatment of these women. "The importance of this finding is that it creates a link between genetic variation and sub-fertility. These women have a normal menstrual cycle and they may present to the fertility centre as patients with unexplained infertility, before their first IVF cycle that would reveal an ovarian stimulation defect," she said.
"Our finding explains why these women have a lower response to FSH. Currently, FSH is the only medication used to stimulate ovarian response, but once other medications are available that can bypass the receptor for FSH, they can be tested on these women. Also, at present we cannot predict if the women would profit from having higher doses of medication, and, in fact, some preliminary data from other groups show the opposite: that lower FSH may be more beneficial."
Future research will examine the FSHR signalling mechanisms within the cell and investigate how newly developed drugs might bypass the problems created by the genetic abnormality. "In the future, this could lead to personalised treatments for a sub-group of patients," said Dr Lalioti.
It is not known how many women have this particular genetic variation. Dr Lalioti found it in two out of five women that she tested. "These patients are hard to recruit because most patients with a low response to FSH do not complete the IVF cycle for financial reasons," she said. "We need to recruit more patients to discover how common it is." She and her colleagues will need a year to recruit and test more women, to set up collaborations with more fertility centres and to start to test new drugs that could promote oocyte production more effectively in these women.
Dr Maria Lalioti told the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome today (Tuesday) that she and her colleagues from the Yale University Medical School, New Haven (USA), had found that some women had an abnormal hormone receptor on cells surrounding oocytes (eggs). This abnormal receptor impaired the function of normal receptors that were also present and resulted in the affected women responding less well to Follicle Stimulating Hormone (FSH), which is given to women during fertility treatment to stimulate the production of more than one oocyte.
Dr Lalioti, as assistant professor in the Department of Obstetrics Gynecology and Reproductive Sciences at Yale, said: "When a woman undergoes in vitro fertilisation, she receives medication called Follicle Stimulating Hormone to produce more than one oocyte, which is the normal production each month. Cells called granulosa cells, which surround the oocyte, receive the FSH; these cells excrete other factors that ‘feed’ the oocyte. The granulosa cells have proteins present on their surface called FSH receptors (or FSHR) and it is these proteins that stick to the FSH and then carry signals into the cell’s interior. When we looked at a portion of these granulosa cells in the laboratory we saw that in some women, who produced very few oocytes, there were some receptors that lacked a piece of the protein, although there were still other, normal FSHR in the women’s cells."
The abnormal FSHR contained a deleted sequence of protein called exon 2 that is an important part of the protein that binds the FSH; FSHR with the exon 2 deletion was only detected in women younger than 35 who had a poor response to FSH and yielded less than four oocytes in a follicle stimulating cycle.
"We produced the normal and abnormal protein in the lab in a different type of cell called HEK293 (Human Embryonic Kidney) which is a common cell type used in the labs to examine properties of proteins. We saw that when the abnormal receptor was present, the normal one could no longer work as well as it does when it is the only protein present," explained Dr Lalioti. "The receptor is normally present on the cell surface in order to meet and bind FSH, and it needs to go through a number of cellular checkpoints inside the cell that assure the quality of the protein presented on the surface. We saw that the abnormal receptor remains longer in one of these checkpoint compartments, indicating that the cell has detected a problem and is trying to correct it. In this way the abnormal FSHR can contribute to an abnormally low response to stimulation in certain women undergoing IVF."
Dr Lalioti’s discovery of the mechanism behind why some young women have a poor response to FSH has important implications for future research and treatment of these women. "The importance of this finding is that it creates a link between genetic variation and sub-fertility. These women have a normal menstrual cycle and they may present to the fertility centre as patients with unexplained infertility, before their first IVF cycle that would reveal an ovarian stimulation defect," she said.
"Our finding explains why these women have a lower response to FSH. Currently, FSH is the only medication used to stimulate ovarian response, but once other medications are available that can bypass the receptor for FSH, they can be tested on these women. Also, at present we cannot predict if the women would profit from having higher doses of medication, and, in fact, some preliminary data from other groups show the opposite: that lower FSH may be more beneficial."
Future research will examine the FSHR signalling mechanisms within the cell and investigate how newly developed drugs might bypass the problems created by the genetic abnormality. "In the future, this could lead to personalised treatments for a sub-group of patients," said Dr Lalioti.
It is not known how many women have this particular genetic variation. Dr Lalioti found it in two out of five women that she tested. "These patients are hard to recruit because most patients with a low response to FSH do not complete the IVF cycle for financial reasons," she said. "We need to recruit more patients to discover how common it is." She and her colleagues will need a year to recruit and test more women, to set up collaborations with more fertility centres and to start to test new drugs that could promote oocyte production more effectively in these women.
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