| Female reproductive regulation is one of the most complicated system in human body. At first reported in the 1950s, much evidence had accumulated showing that female reproductive functions were significantly correlated with nutritional status. Normal cycles might be disrupted by severe over- or under-nutrition. However, the mechanism still eludes gynecologists. At the end of 1994, Zhang and his colleagues succeeded in positional cloning of the mouse obese gene and its human homologue. The obese gene product, leptin, is a 167 aminoacid and a 16KD protein hormone that is mainly produced and secreted by adipocytes. As a peripheral afferent signal of nutritional status in hypothalamus, leptin plays a role in the regulation of fat stores and energy metabolism. Recently, the relationship between leptin and reproduction has been attracted more interest. It has been found that the ob/ob mice with obese gene mutation would fail to synthesize the leptin and became very obese and infertile, while treatment with leptin could reduce weight and restores fertility. In human, genetic leptin deficiency is rare. Individuals with gene mutation are obese and remain prepubertal with hypogonadotrophic hypogonadism. Hence, Barash suggested that leptin be a metabolic signal to the reproductive system. Leptin receptors have been demonstrated in the hypothalamus, pituitary, ovary and uterine. And leptin has been found to have a stimulating effect on the hypothalamic output of luteinizing hormone releasing hormone (LHRH) and on the pituitary output of gonadotrophin. So, it isgenerally considered thought that leptin affects reproduction by regulating the hypothalamic-pituitary-ovary axis.Compared with the researches that leptin involved in adipocyte metabolism and energy metabolism, the reports about leptin in the reproductive regulatory were relatively less, in which the studies were mainly focused on hypothalamic and pituitary. So far, whether leptin has a directly role on ovary, whether ovary could secret leptin and its function on follicular development were unknown. In our country, the reports about relationship between leptin and reproduction have not been published up to now. The purpose of the research was to examine the effect of leptin on the mechanism of reproductive regulation from different aspects. (1) The investigation of the changes of leptin concentrations in serum and pre-ovulatory follicular fluid during natural and control ovarian hyperstimulation (COH ) cycles were carried out. (2) Therefore, leptin physiological levels in natural cycles, action of superovulation on leptin concentration and relationship between leptin concentration and outcome of IVF were assessed. (3) The expression of messenger RNA for granulosa cells leptin and leptin receptors was examined.Meterials and MethodsBlood samples were obtained from twelve young volunteer women with regular menstrual cycles at menstrual phase (day 3 ), late proliferate phase (day 13 ), and luteal phase (day 23 ) respectively. Meanwhile, blood samples and follicular fluid were collected from ten age-matched women with regular menstrual cycles who underwent an abdominal laparotomy for myoma of uterus or tube rejoining for sterilization in pre-ovulatory phase. In addition, thirty-nine women who underwent IVF-ET with long protocol because of tubal infertility were enrolled in this study, in which blood samples were collected just before injection of FSH, injection of HCG and follicles puncture. Follicular fluid was collected at the time of oocyte retrieval. Leptin and E2 levels were measured by enzyme-linked immunosorbent assay using a commercially available ELISA kit and radioimmunoassay respectively. The dosage and duration of gonadotrophin used, the number of oocytes retrieved and fertilized and the number of embryos transferred were recorded. Reverse transcription-PCR was applied to determine the expression of leptin mRNA and leptin receptor mRNA in human granulosa cells. Statistical calculations were done by SPSS 9.0 for windows .ResultsIn t... |
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