Reproductive Biology and Endocrinology | |
High-fat diet decreases the expression of Kiss1 mRNA and kisspeptin in the ovary, and increases ovulatory dysfunction in postpubertal female rats | |
Xueqing Wu1  Yuanyuan Chen1  Binqiao Wang1  Yuehua Li1  Simeng Yang1  Haiyan Chen1  Qiangyong Zhou1  | |
[1] Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China | |
关键词: Ovulation; Oestrous cycle; Kisspeptin; Kiss1; High-fat diet; | |
Others : 1132317 DOI : 10.1186/1477-7827-12-127 |
|
received in 2014-09-02, accepted in 2014-12-15, 发布年份 2014 | |
【 摘 要 】
Background
Female reproductive health is noticeably compromised by obesity. The underlying mechanisms remain to be elucidated. Accumulating evidence indicates that the expression level of ovarian Kiss1 peaks in the afternoon during prooestrus, suggesting local regulatory roles for Kiss1 in the ovulatory process. We used a diet-induced model of obesity to evaluate whether the ovarian Kiss1 system is affected by obesity, and, to investigate the association of the Kiss1 system with ovulatory disorders in female rats.
Methods
Post-weaning, female, Sprague–Dawley rats were randomly fed either a high-fat diet (HFD) or a normal chow diet (NCD) until they reached postnatal day 30 (PND 30), PND 42, or PND 70. The timing of vaginal opening was recorded, and oestrous cyclicity was monitored for 2 consecutive weeks immediately post puberty and again at 8–9 weeks of age. Tissues from the left ovary were collected for determination of the levels of Kiss1 and G protein-coupled receptor 54 (GPR54) mRNA, and tissues from the right ovary were collected for assessment of the immunoreactivity (IR) of the corresponding protein products, kisspeptin and GPR54.
Results
The high-fat diet resulted in a significantly higher body weight and an earlier puberty onset. Oestrous cyclicity was disrupted by the HFD with significant reductions in the expression of ovulation-related genes. A marked suppression of ovarian Kiss1 mRNA levels was observed during prooestrus and oestrus at PND 42, and, during prooestrus, oestrus, and metoestrus at PND 70 in the HFD rats compared with the NCD controls. In the HFD group, the immunoreactivity of kisspeptin was significantly lower in theca cells from antral follicles during prooestrus and oestrus at PND 42, and, during prooestrus, oestrus at PND 70. At the prooestrus stage, in the HFD group the immunoreactivity of kisspeptin was also lower in the theca cells of preovulatory follicles at both PND 42 and PND 70.
Conclusions
Exposure of female rats to an post-weaning, high-fat diet has long-term deleterious effects on ovulation, that may involve down-regulation of ovarian Kiss1 mRNA and kisspeptin.
【 授权许可】
2014 Zhou et al.; licensee BioMed Central.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150303154548253.pdf | 3338KB | download | |
Figure 8. | 194KB | Image | download |
Figure 7. | 220KB | Image | download |
Figure 6. | 276KB | Image | download |
Figure 5. | 73KB | Image | download |
Figure 4. | 41KB | Image | download |
Figure 3. | 58KB | Image | download |
Figure 2. | 41KB | Image | download |
Figure 1. | 61KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.
【 参考文献 】
- [1]James PT: Obesity: the worldwide epidemic. Clin Dermatol 2004, 22:276-280.
- [2]Wang Y, Beydoun MA: The obesity epidemic in the United States–gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiol Rev 2007, 29:6-28.
- [3]Aggerholm AS, Thulstrup AM, Toft G, Ramlau-Hansen CH, Bonde JP: Is overweight a risk factor for reduced semen quality and altered serum sex hormone profile? Fertil Steril 2008, 90:619-626.
- [4]Brewer CJ, Balen AH: The adverse effects of obesity on conception and implantation. Reproduction 2010, 140:347-364.
- [5]Davies GA, Maxwell C, McLeod L, Gagnon R, Basso M, Bos H, Delisle MF, Farine D, Hudon L, Menticoglou S, Mundle W, Murphy-Kaulbeck L, Ouellet A, Pressey T, Roggensack A, Leduc D, Ballerman C, Biringer A, Duperron L, Jones D, Lee LS, Shepherd D, Wilson K: Obesity in pregnancy. J Obstet Gynaecol Can 2010, 32:165-173.
- [6]Pandey S, Bhattacharya S: Impact of obesity on gynecology. Womens Health 2010, 6:107-117.
- [7]Li XF, Lin YS, Kinsey-Jones JS, O'Byrne KT: High-fat diet increases LH pulse frequency and kisspeptin-neurokinin B expression in puberty-advanced female rats. Endocrinology 2012, 153:4422-4431.
- [8]Terasawa E, Kurian JR, Keen KL, Shiel NA, Colman RJ, Capuano SV: Body weight impact on puberty: effects of high-calorie diet on puberty onset in female rhesus monkeys. Endocrinology 2012, 153:1696-1705.
- [9]Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M: Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev 2012, 92:1235-1316.
- [10]Adachi S, Yamada S, Takatsu Y, Matsui H, Kinoshita M, Takase K, Sugiura H, Ohtaki T, Matsumoto H, Uenoyama Y, Tsukamura H, Inoue K, Maeda K: Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats. J Reprod Dev 2007, 53:367-378.
- [11]Castellano JM, Gaytan M, Roa J, Vigo E, Navarro VM, Bellido C, Dieguez C, Aguilar E, Sánchez-Criado JE, Pellicer A, Pinilla L, Gaytan F, Tena-Sempere M: Expression of KiSS-1 in rat ovary: putative local regulator of ovulation? Endocrinology 2006, 147:4852-4862.
- [12]Shahed A, Young KA: Differential ovarian expression of KiSS-1 and GPR-54 during the estrous cycle and photoperiod induced recrudescence in Siberian hamsters (Phodopus sungorus). Mol Reprod Dev 2009, 76:444-452.
- [13]Gaytan F, Gaytan M, Castellano JM, Romero M, Roa J, Aparicio B, Garrido N, Sánchez-Criado JE, Millar RP, Pellicer A, Fraser HM, Tena-Sempere M: KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction. Am J Physiol Endocrinol Metab 2009, 296:E520-E531.
- [14]Castellano JM, Navarro VM, Fernandez-Fernandez R, Nogueiras R, Tovar S, Roa J, Vazquez MJ, Vigo E, Casanueva FF, Aguilar E, Pinilla L, Dieguez C, Tena-Sempere M: Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 2005, 146:3917-3925.
- [15]Matsuzaki T, Iwasa T, Kinouchi R, Yoshida S, Murakami M, Gereltsetseg G, Yamamoto S, Kuwahara A, Yasui T, Irahara M: Fasting reduces the kiss1 mRNA levels in the caudal hypothalamus of gonadally intact adult female rats. Endocr J 2011, 58:1003-1012.
- [16]Quennell JH, Howell CS, Roa J, Augustine RA, Grattan DR, Anderson GM: Leptin deficiency and diet-induced obesity reduce hypothalamic kisspeptin expression in mice. Endocrinology 2011, 152:1541-1550.
- [17]Wu XQ, Li XF, Ye B, Popat N, Milligan SR, Lightman SL, O'Byrne KT: Neonatal programming by immunological challenge: effects on ovarian function in the adult rat. Reproduction 2011, 141:241-248.
- [18]Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008, 3:1101-1108.
- [19]Gaytan M, Castellano JM, Roa J, Sanchez-Criado JE, Tena-Sempere M, Gaytan F: Expression of KiSS-1 in rat oviduct: possible involvement in prevention of ectopic implantation? Cell Tissue Res 2007, 329:571-579.
- [20]Wan SM, Tie J, Zhang YF, Guo J, Yang LQ, Wang J, Xia SH, Yang SM, Wang RQ, Fang DC: Silencing of the hPOT1 gene by RNA inference promotes apoptosis and inhibits proliferation and aggressive phenotype of gastric cancer cells, likely through up-regulating PinX1 expression. J Clin Pathol 2011, 64:1051-1057.
- [21]Cui LL, Li P, Zhu ZY: Impact of changes in postnatal nutrition on puberty onset and the expression of hypothalamic GnRH and ghrelin. Eur Rev Med Pharmacol Sci 2014, 18:703-709.
- [22]Cordier AG, Leveille P, Dupont C, Tarrade A, Picone O, Larcher T, Dahirel M, Poumerol E, Mandon-Pepin B, Lévy R, Chavatte-Palmer P: Dietary lipid and cholesterol induce ovarian dysfunction and abnormal LH response to stimulation in rabbits. PLoS One 2013, 8:e63101.
- [23]Bau AM, Ernert A, Schenk L, Wiegand S, Martus P, Gruters A, Krude H: Is there a further acceleration in the age at onset of menarche? A cross-sectional study in 1840 school children focusing on age and bodyweight at the onset of menarche. Eur J Endocrinol 2009, 160:107-113.
- [24]Macsali F, Real FG, Plana E, Sunyer J, Anto J, Dratva J, Janson C, Jarvis D, Omenaas ER, Zemp E, Wjst M, Leynaert B, Svanes C: Early age at menarche, lung function, and adult asthma. Am J Respir Crit Care Med 2011, 183:8-14.
- [25]Weghofer A, Kim A, Barad DH, Gleicher N: Age at menarche: a predictor of diminished ovarian function? Fertil Steril 2013, 100:1039-1043.
- [26]Ozdemir O, Col M: The age at menopause and associated factors at the health center area in Ankara, Turkey. Maturitas 2004, 49:211-219.
- [27]Lie ME, Overgaard A, Mikkelsen JD: Effect of a postnatal high-fat diet exposure on puberty onset, estrous cycle regularity, and kisspeptin expression in female rats. Reprod Biol 2013, 13:298-308.
- [28]Smith JT, Spencer SJ: Preweaning over- and underfeeding alters onset of puberty in the rat without affecting kisspeptin. Biol Reprod 2012, 86:145. 1–8
- [29]Kamara K, Eskay R, Castonguay T: High-fat diets and stress responsivity. Physiol Behav 1998, 64:1-6.
- [30]Ricu MA, Ramirez VD, Paredes AH, Lara HE: Evidence for a celiac ganglion-ovarian kisspeptin neural network in the rat: intraovarian anti-kisspeptin delays vaginal opening and alters estrous cyclicity. Endocrinology 2012, 153:4966-4977.
- [31]Ginther OJ, Pinaffi FL, Khan FA, Duarte LF, Beg MA: Circadian influence on the preovulatory LH surge, ovulation, and prolactin concentrations in heifers. Theriogenology 2013, 79:528-533.
- [32]Balasubramanian P, Jagannathan L, Mahaley RE, Subramanian M, Gilbreath ET, Mohankumar PS, Mohankumar SM: High fat diet affects reproductive functions in female diet-induced obese and dietary resistant rats. J Neuroendocrinol 2012, 24:748-755.
- [33]Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N: Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab 2007, 92:2468-2473.
- [34]Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, Malli R, Sharabi A, Hiden U, Graier W, Knofler M, Andreae F, Wagner O, Quaranta V, Desoye G: Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci 2004, 117:1319-1328.
- [35]Ny T, Wahlberg P, Brandstrom IJ: Matrix remodeling in the ovary: regulation and functional role of the plasminogen activator and matrix metalloproteinase systems. Mol Cell Endocrinol 2002, 187:29-38.
- [36]Peng J, Tang M, Zhang BP, Zhang P, Zhong T, Zong T, Yang B, Kuang HB: Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signaling pathway in rat luteal cells. Fertil Steril 2013, 99:1436-1443.
- [37]Balasch J, Fabregues F, Carmona F, Casamitjana R, Tena-Sempere M: Ovarian luteinizing hormone priming preceding follicle-stimulating hormone stimulation: clinical and endocrine effects in women with long-term hypogonadotropic hypogonadism. J Clin Endocrinol Metab 2009, 94:2367-2373.
- [38]Jayasena CN, Abbara A, Veldhuis JD, Comninos AN, Ratnasabapathy R, De Silva A, Nijher GM, Ganiyu-Dada Z, Mehta A, Todd C, Ghatei MA, Bloom SR, Dhillo WS: Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54. J Clin Endocrinol Metab 2014, 99:E953-E961.
- [39]Jayasena CN, Comninos AN, Veldhuis JD, Misra S, Abbara A, Izzi-Engbeaya C, Donaldson M, Ghatei MA, Bloom SR, Dhillo WS: A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women. Clin Endocrinol 2013, 79:558-563.