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Leptin exerts many biological functions,such as in metabolism and reproduction,through binding to and activating the leptin receptor,LepRb,which is expressed in many regions of the brain.To better understand the roles of LepR in reproduction and involved downstream signaling pathways,Y123F mice,which expressed mutant leptin receptors with phenylalanine (F) substituted for three tyrosines (Y) (Tyr985,Tyr1077 and Tyr1 138),were generated.OBJECTIVE To observe reproductive phenotypes caused by LepR gene site mutation by comparing Y123F (HOM) and wild type (VVT) mouse ovaries,to explore involved gene expression profiling,and to evaluate whether homozygous gene mutation (LepR-/-) mouse can be used as a new polycystic ovary syndrome (PCOS) animal model.Materials and Methods Female Y123F HOM and WT mice;Obesity phenotypic evaluation,estrous cycle,blood estrogen level,LepR expression,cDNA Microarrays and Real-time quantitative PCR analysis on mRNA levels.RESULT(S) The body weight and abdominal fat deposits of Y123F homozygous mice (HOM) were higher than those of wild-type mice (WT).HOM ovaries were atrophic and the follicles developed abnormally;however,the HOM ovaries did not exhibit polycystic phenotypes.Moreover,Y123F HOM adults had no estrous cycle and the blood estrogen concentration remained stable at a low level below detection limit of 5 pg/ml.LepR expression in HOM ovaries was higher than in WT ovaries.Using cDNA Microarrays,the mRNA expressions of 41 genes were increased,and 100 were decreased in HOM vs.WT ovaries,and many signaling pathways were evaluated to be involved significantly.The expressions of 19 genes were validated by real-time quantitative PCR,most of which were consistent with the microarray results.CONCLUSION(S) Y123F HOM mice were suggested as a new animal model of PCOS for research that mainly emphasizes metabolic disorders and anovulation,but not the polycystic phenotype.Meanwhile,using the model,we found that JAK-STAT and hormone biosynthesis pathways were involved in the follicular development and ovulation disorders caused by LepR deficiency in ovaries,although we could not exclude indirect actions from the brain.