Altered expression of the kisspeptin/KISS1R and neurokinin B/NK3R systems in mural granulosa and cumulus cells of patients with polycystic ovarian syndrome

• Published in: Journal of assisted reproduction and genetics 2019-01, Vol.36 (1), p.113-120
• Main Authors: Blasco, Victor, Pinto, Francisco M., Fernández-Atucha, Ainhoa, Prados, Nicolás, Tena-Sempere, Manuel, Fernández-Sánchez, Manuel, Candenas, Luz
• Format: Article
• Language: English
• Subjects: Adult; Case-Control Studies; Cells, Cultured; Cross-Sectional Studies; Cumulus Cells - metabolism; Cumulus Cells - pathology; Female; Fertility; Follicles; Gene Expression Regulation; Gonads; Granulosa cells; Granulosa Cells - metabolism; Granulosa Cells - pathology; Gynecology; Human Genetics; Humans; Kiss1 protein; Kisspeptins - genetics; Kisspeptins - metabolism; Medicine; Medicine & Public Health; mRNA; Neurokinin; Neurokinin B; Neurokinin B - genetics; Neurokinin B - metabolism; Ovulation; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Polycystic Ovary Syndrome - pathology; Polymerase chain reaction; Receptors, Kisspeptin-1 - genetics; Receptors, Kisspeptin-1 - metabolism; Receptors, Neurokinin-3 - genetics; Receptors, Neurokinin-3 - metabolism; Reproductive Medicine; Reproductive Physiology and Disease; Ultrasound; Young Adult
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-018-1338-7

Purpose The neurokinin B (NKB)/NK 3 receptor (NK3R) and kisspeptin (KISS1)/kisspeptin receptor (KISS1R), two systems essential for reproduction, are present in human granulosa cells (GCs) of healthy women and contribute to the control of fertility, at least partially, by acting on the gonads. However, little is known about the expression of these systems in GCs of women with polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the expression of NKB/NK3R and KISS1/KISS1R in mural granulosa (MGCs) and cumulus cells (CCs) of PCOS women. Methods A cross-sectional study was performed in 46 healthy women and 43 PCOS women undergoing controlled ovarian stimulation. MGCs and CCs were collected from pre-ovulatory follicles after transvaginal ultrasound-guided oocyte retrieval and the expression of the genes encoding NKB ( TAC3 ), NK3R ( TACR3 ), KISS1 , and its receptor ( KISS1R ) was analyzed using real-time quantitative RT-PCR. Results TAC3 , TACR3 , and KISS1 mRNA levels were decreased in MGCs and CCs of PCOS women. TAC3 positively correlated with KISS1 in MGCs of healthy women and TACR3 was positively associated with KISS1R in CCs from healthy women. These associations were not observed in PCOS women. Conclusion The NKB/NK3R and KISS1/KISS1R systems are dysregulated in MGCs and CCs of PCOS women. The lower expression of these systems in GCs could contribute to the abnormal follicle development and defective ovulation that characterize the pathogenesis of PCOS.