Endocrine Abstracts (2018) 56 OC2.2 | DOI: 10.1530/endoabs.56.OC2.2

Overexpressed kisspeptin/Kiss1R system in human granulosa cells may be involved in the pathogenesis of polycystic ovary syndrome (PCOS) by inhibiting ovulation

Kai-Lun Hu & Yang Yu

Peking University Third Hospital, Beijing, China.

The kisspeptin/Kiss1R and neurokinin B (NKB)/ tachykinin receptor 3 (TACR3) system in the hypothalamus are essential for reproduction. Recent study suggested that the two peptide systems were both expressed in the ovary, particularly in the granulosa cells. To investigate the two systems in regulating the ovarian function, we collected the granulosa cells and follicular fluids from the 80 infertile patients (42 infertile control women and 38 PCOS women) undergoing IVF in Peking University Third Hospital. The mRNA expression of Kiss1, Kiss1R, Tac3, Tacr3, MMP9 and COX2 in the collected granulosa cells were tested by quantitative RT-PCR and the concentration of kisspeptin and NKB in the follicular fluids were tested using ELISA kit. Circulating levels of hormones were measured with the radioimmunoassay method. We found that Kiss1 and Kiss1R were significantly upregulated in the granulosa cells from patients with polycystic ovary syndrome (PCOS) compared to the normal control (both P<0.01), but no significant difference was detected between the obese group (BMI>25) and the non-obese group (BMI≤25). The expression of Tac3 and Tacr3 did not show significant difference between the PCOS group and normal control group, but they were significantly downregulated in the obese group (both P<0.01). Interestingly, both the expression of Kiss1 and Tac3 were highly correlated with their receptor gene, respectively (both P<0.0001). Additionally, Kiss1 mRNA level was correlated with the serum AMH levels (P<0.01). While Kiss1R mRNA level was correlated with the follicular number (P<0.05). The expression of Kiss1, Kiss1R, Tac3, Tacr3 were not significantly correlated with oocyte maturation rate and circulating hormones levels, including E2, progesterone, follicle-stimulating hormone (FSH), luteinized hormone (LH), and E2, progesterone, LH levels in HCG day. Kisspeptin-10 significantly inhibited the expression of MMP9 and COX2 in a dose-dependent manner, which were attenuated by kisspeptin antagonist, P234. Kisspeptin-10 also significantly upregulated the expression of Tacr3. Senktide, an agonist of TACR3, inhibited the expression of COX2, but not MMP9. Our results suggest that the overexpressed kisspeptin/Kiss1R system in human granulosa cells may be involved in the pathogenesis of PCOS by inhibiting ovulatory function of the ovary. The expression of Kiss1 in the granulosa cells may be an alternative marker for the ovarian reserve.

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