Identification of genes or polypeptides the expression of which correlates to fertility, ovarian function and/or fetal/newborn viability

Abstract

A genetic means of determining whether a female subject produces “pregnancy competent” oocytes is provided. The means comprises detecting the level of expression of one or more genes that are expressed at characteristic levels (upregulated or downregulated) in cumulus cells derived from pregnancy competent oocytes. This characteristic gene expression level, or pattern referred to herein as the “pregnancy signature”, also can be used to identify subjects with underlying conditions that impair or prevent the development of a viable pregnancy, e.g., pre-menopausal condition, other hormonal dysfunction, ovarian dysfunction, ovarian cyst, cancer or other cell proliferation disorder, autoimmune disease and the like. Microarrays containing “pregnancy signature” genes or corresponding polypeptides provide another preferred aspect of the invention. Still further, the subject invention can be used to derive animal models, e.g., non-human primate animal models, for the evaluation of the efficacy of putative female fertility treatments.

1 - 45 . (canceled) 
     
     
         46 . A method of identifying oocytes that are capable of giving rise to a viable pregnancy when fertilized comprising the following steps: (i) obtaining at least one cumulus cell associated with an oocyte; (ii) assaying the expression of at least 5 genes selected from the genes in Table 1, wherein at least 2 of said genes are selected HAS2, PTX3, DHFR, ZNF93, DUSP12, STK35, WTAP, AQP3 by said at least one oocyte associated cell, the expression of which correlates to the capability of an oocyte associated with said cell to yield a viable pregnancy upon fertilization and transferral into a suitable uterine environment; and (iii) identifying, based on the level of expression of said at least one gene, whether said oocytes is potentially capable of yielding a viable pregnancy upon fertilization and transferral into a suitable uterine environment. 
     
     
         47 . The method of  claim 46 , wherein said oocyte is a mammalian oocyte. 
     
     
         48 . The method of  claim 47 , wherein said oocytes is a human oocyte. 
     
     
         49 . The method of  claim 47 , wherein said oocyte is a non-human primate oocyte. 
     
     
         50 . The method of  claim 46 , wherein the expression of at least 10 genes, the expression of which correlates to the capability of an oocyte to potentially yield a viable pregnancy are identified. 
     
     
         51 . The method of  claim 46  wherein said at least one gene additionally includes at least one gene selected from the group consisting of PRMT5, PTG2, ACTB, or a variant thereof possessing at least 95% sequence identity to one of the sequences contained in  FIG. 19 . 
     
     
         52 . The method of  claim 46 , wherein the expression of at least 15 genes, the expression of which correlates to the capability of an oocyte to potentially yield a viable pregnancy are measured. 
     
     
         53 . The method of  claim 46 , wherein the expression of at least 20 genes, the expression of which correlates to the capability of an oocyte to potentially yield a viable pregnancy are identified. 
     
     
         54 . The method of  claim 53 , wherein the expression of at least 20 to 50 genes, the expression of which correlates to the capability of an oocyte to potentially yield a viable pregnancy are identified. 
     
     
         55 . The method of  claim 54 , wherein the expression of at least 50 to 100 genes, the expression of which correlates to the capability of an oocyte to potentially yield a viable pregnancy are identified. 
     
     
         56 . The method of  claim 46  wherein the method of assaying gene expression uses a method that monitors differential gene expression. 
     
     
         57 . The method of  claim 56  wherein said method comprises indexing differential display reverse transcriptase polymerase chain reaction (DDRT-PCR).