Le Kremlin-Bicêtre, France
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Sarfati J.,Center Hospitalier University Of Bicetre Aphp | Young J.,Center Hospitalier University Of Bicetre Aphp | Young J.,University Paris - Sud | Christin-Maitre S.,University Paris - Sud
Annales d'Endocrinologie | Year: 2010

The aim of this review is to underscore the major role of forkhead proteins in the adult ovary. Indeed, they revolutionize the idea of terminal differentiation of adult tissues with for example the in vivo reprogrammation of an adult organism on the one hand, and, on the other hand, the therapeutic possibilities of fertility preservation in women. In mammals, SRY, a transcription factor encoded by the Y chromosome, is responsible for the development of the undifferentiated gonads into testes. However, testis differentiation can occur in its absence. The studies of M. Treier demonstrate that FOXL2 is required to maintain the ovarian phenotype. Indeed, the absence of Foxl2 in an adult mouse ovary leads to an up regulation of testis-specific genes and a transformation of granulosa and theca cells into Sertoli-like and Leydig-like cells. The maintenance of the ovarian phenotype is an active process throughout life. Although multiple follicles are present in mammalian ovaries, most of them remain dormant. During reproductive life, some follicles are activated for development. There is an inefficient activation of dormant follicles within cryopreserved ovaries. An inhibition of the FOXO3a pathway in the mouse ovary leads to an enhancement of the activation of the dormant follicles. After transplantation, there are more preovulatory stage follicles and, after fertilization and embryo transfer, they lead to a healthy progeny. In human ovarian cortical fragments, the same inhibition and a xenotransplantation permit a development of more primordial follicles to the preovulatory stage. Thus, this treatment may be a hope to treat infertile women with cryopreserved ovaries or with a diminishing ovarian reserve. © 2010 Elsevier Masson SAS.


Sarfati J.,Center Hospitalier University Of Bicetre Aphp | Young J.,Center Hospitalier University Of Bicetre Aphp | Young J.,University Paris - Sud | Christin-Maitre S.,University Paris - Sud
Annales d'Endocrinologie | Year: 2010

Weight, fat mass and obesity have been shown to play a major role in female reproduction. Obese women have a greater risk than nonobese women of infertility and they fail to become pregnant in both natural and assisted conception cycles. This cannot be explained only by their lack of ovulation. There are several potential mechanisms. On one hand, the endometrium seems to be partially responsible for this low fecundity in obese women. On the other hand, the oocyte seems to be implied. In a model of obese mouse, maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and an increased generation of reactive oxygen species (ROS). Furthermore, compared with controls, obese mice have significantly more decreased embryonic IGF-IR staining, smaller fetuses and smaller pups. In this model, all weaned pups have been fed with a regular diet. At 13 weeks, pups delivered from obese mice were significantly larger, and these pups demonstrated early development of a metabolic-type syndrome. These findings suggest that maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stages and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception. © 2010 Elsevier Masson SAS.


PubMed | Center Hospitalier University Of Bicetre Aphp
Type: | Journal: Annales d'endocrinologie | Year: 2011

The aim of this review is to underscore the major role of forkhead proteins in the adult ovary. Indeed, they revolutionize the idea of terminal differentiation of adult tissues with for example the in vivo reprogrammation of an adult organism on the one hand, and, on the other hand, the therapeutic possibilities of fertility preservation in women. In mammals, SRY, a transcription factor encoded by the Y chromosome, is responsible for the development of the undifferentiated gonads into testes. However, testis differentiation can occur in its absence. The studies of M. Treier demonstrate that FOXL2 is required to maintain the ovarian phenotype. Indeed, the absence of Foxl2 in an adult mouse ovary leads to an up regulation of testis-specific genes and a transformation of granulosa and theca cells into Sertoli-like and Leydig-like cells. The maintenance of the ovarian phenotype is an active process throughout life. Although multiple follicles are present in mammalian ovaries, most of them remain dormant. During reproductive life, some follicles are activated for development. There is an inefficient activation of dormant follicles within cryopreserved ovaries. An inhibition of the FOXO3a pathway in the mouse ovary leads to an enhancement of the activation of the dormant follicles. After transplantation, there are more preovulatory stage follicles and, after fertilization and embryo transfer, they lead to a healthy progeny. In human ovarian cortical fragments, the same inhibition and a xenotransplantation permit a development of more primordial follicles to the preovulatory stage. Thus, this treatment may be a hope to treat infertile women with cryopreserved ovaries or with a diminishing ovarian reserve.


PubMed | Center Hospitalier University Of Bicetre Aphp
Type: | Journal: Annales d'endocrinologie | Year: 2011

Weight, fat mass and obesity have been shown to play a major role in female reproduction. Obese women have a greater risk than nonobese women of infertility and they fail to become pregnant in both natural and assisted conception cycles. This cannot be explained only by their lack of ovulation. There are several potential mechanisms. On one hand, the endometrium seems to be partially responsible for this low fecundity in obese women. On the other hand, the oocyte seems to be implied. In a model of obese mouse, maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and an increased generation of reactive oxygen species (ROS). Furthermore, compared with controls, obese mice have significantly more decreased embryonic IGF-IR staining, smaller fetuses and smaller pups. In this model, all weaned pups have been fed with a regular diet. At 13 weeks, pups delivered from obese mice were significantly larger, and these pups demonstrated early development of a metabolic-type syndrome. These findings suggest that maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stages and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception.

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