sirolimus and Infertility--Female

Maternal aging-associated reduction of oocyte viability is a common feature in mammals, but more research is needed to counteract this process. In women, the first aging phenotype appears with a decline in reproductive function, and the follicle number gradually decreases from menarche to menopause. Cows can be used as a model of early human embryonic development and reproductive aging because both species share a very high degree of similarity during follicle selection, cleavage, and blastocyst formation. Recently, it has been proposed that the main driver of aging is the mammalian target of rapamycin (mTOR) signaling rather than reactive oxygen species. Based on these observations, the study aimed to investigate for the first time the possible role of rapamycin on oocyte maturation, embryonic development, and telomere length in the bovine species, as a target for future strategies for female infertility caused by advanced maternal age. The 1nm rapamycin

Topics: Animals; Cattle; Disease Models, Animal; Embryonic Development; Female; In Vitro Oocyte Maturation Techniques; Infertility, Female; Metaphase; Oocytes; Ovarian Follicle; Pregnancy; Pregnancy, Animal; Sirolimus; Telomere Homeostasis

There are few treatments for patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Women with RPL and unexplained infertility have lower T regulatory cell (T

Topics: Animals; Birth Rate; Disease Models, Animal; Embryo Implantation; Female; Immunosuppressive Agents; Infertility, Female; Live Birth; Lymphocyte Depletion; Mice; Sirolimus; T-Lymphocytes, Regulatory

Mice lacking p27(Kip1) have been created by gene targeting in embryonic stem cells. These mice are larger than the control animals, with thymus, pituitary, and adrenal glands and gonadal organs exhibiting striking enlargement. CDK2 activity is elevated about 10-fold in p27(-/-) thymocytes. Development of ovarian follicles seems to be impaired, resulting in female sterility. Similar to mice with the Rb mutation, the p27(-/-) mice often develop pituitary tumors spontaneously. The retinas of the mutant mice show a disturbed organization of the normal cellular layer pattern. These findings indicate that p27(Kip1) acts to regulate the growth of a variety of cells. Unexpectedly, the cell cycle arrest mediated by TGFbeta, rapamycin, or contact inhibition remained intact in p27(-/-) cells, suggesting that p27(Kip1) is not required in these pathways.

Topics: Animals; Base Sequence; Body Constitution; Cell Cycle; Cell Cycle Proteins; Cell Division; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases; DNA Primers; DNA, Complementary; Enzyme Inhibitors; Female; Gene Expression; Gene Targeting; Genes, Tumor Suppressor; Heterozygote; Hyperplasia; Infertility, Female; Male; Mice; Mice, Knockout; Microtubule-Associated Proteins; Molecular Sequence Data; Phenotype; Pituitary Neoplasms; Polyenes; Retinal Dysplasia; Sirolimus; Tissue Distribution; Transforming Growth Factor alpha; Tumor Suppressor Proteins