Patatin-like phospholipase domain containing 3-gene (adiponutrin), preptin, kisspeptin and amylin regulates oocyte developmental capacity in PCOS

Nilufer Celik; Suleyman Aydin; Kader Ugur; Meltem Yardim; Mustafa Acet; Seyda Yavuzkir; ć°brahim Sahin; Onder Celik

doi:10.14715/cmb/2017.64.15.2

Issue

Vol. 64 No. 15: Issue 15

Issue Published : January 1, 2019

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Patatin-like phospholipase domain containing 3-gene (adiponutrin), preptin, kisspeptin and amylin regulates oocyte developmental capacity in PCOS

https://doi.org/10.14715/cmb/2017.64.15.2

Nilufer Celik

Department of Biochemistry, BehcetUz Children's Hospital, ć°zmir, Turkey

Suleyman Aydin

Department of Medical Biochemistry (Firat Hormones Research Group), Firat University, School of Medicine, Elazig, Turkey

Kader Ugur

Department of Internal Medicine, Faculty of Medicine, Firat University, Elazig, Turkey

Meltem Yardim

Department of Medical Biochemistry (Firat Hormones Research Group), Firat University, School of Medicine, Elazig, Turkey

Mustafa Acet

Private Clinic, Obstetrics and Gynecology, Istanbul, Turkey

Seyda Yavuzkir

Department of Obstetrics and Gynecology, Faculty of Medicine, Firat University, Elazig, Turkey

ć°brahim Sahin

Department of Medical Biochemistry (Firat Hormones Research Group), Firat University, School of Medicine, Elazig, Turkey

Onder Celik

Private Clinic, Obstetrics and Gynecology, Usak, Turkey

Corresponding Author(s) : Suleyman Aydin

saydin1@hotmail.com

Cellular and Molecular Biology, Vol. 64 No. 15: Issue 15
Article Published : December 31, 2018

Abstract

This study was planned to test whether follicular fluid (FF) levels of patatin-like phospholipase domain containing 3-gene (PNPLA3:adiponutrin), preptin, kisspeptin, and amylin change in polycystic ovarian syndrome (PCOS). A total of 40 infertile volunteers undergoing IVF/ICSI were included in the study. They were divided into two groups as PCOS (n=20) and control group without PCOS (n=20). The controls were recruited from subjects with a poor ovarian response. The PCOS and control participants were matched according to their body mass index (BMI). Each group of participants underwent ovarian stimulation with GnRH antagonist protocol. Blood and FF samples of one dominant follicle were obtained from each subject during the oocyte pick-up. FF and serum levels of PNPLA3, preptin, kisspeptin and amylin were measured through ELISA. Amylin and adiponutrin median values were not different according to study groups (p>0.05). FF-preptin median values in the control group were similar to the serum preptin values of control and PCOS groups (Z=0.970, p=1.000 and Z=2.631, p=0.051, respectively). Medians of the serum preptin in control and PCOS groups were the same (Z=1.649; p=0.595). FF-preptin median values of PCOS group were significantly lower than the preptin median values of the control group. Serum preptin levels were positively correlated with HOMA-IR, but not with pregnancy rates and the number of retrieved oocytes. Serum kisspeptin levels were negatively correlated with the number of retrieved oocytes and pregnancy rates. While amylin and adiponutrin have no role in the folliculogenesis, kisspeptin and preptin work together for regulating follicle developmental capacity in PCOS.

Keywords

PCOS Follicular fluid IVF/ICSI PNPLA3 Preptin Kisspeptin Amylin.

Celik, N., Aydin, S., Ugur, K., Yardim, M., Acet, M., Yavuzkir, S., Sahin, ć°brahim, & Celik, O. (2018). Patatin-like phospholipase domain containing 3-gene (adiponutrin), preptin, kisspeptin and amylin regulates oocyte developmental capacity in PCOS. Cellular and Molecular Biology, 64(15), 7–12. https://doi.org/10.14715/cmb/2017.64.15.2

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References

Orsi NM, Gopichandran N, Leese HJ, Picton HM, Harris SE. Fluctuations in bovine ovarian follicular fluid composition throughout the oestrous cycle. Reprod 2005; 129:219–28.
Spitzer D, Murach KF, Lottspeich F, Staudach A, Illmensee K. Different protein patterns derived from follicular fluid of mature and immature human follicles. Hum Reprod 1996; 11:798–807.
Leroy JL, Vanholder T, Delanghe JR, Opsomer G, Van Soom A, Bols PE, et al. Metabolite and ionic composition of follicular fluid from different-sized follicles and their relationship to serum concentrations in dairy cows. Anim Reprod Sci 2004; 80:201–11.
Acet M, Celik N, Acet T, Ilhan S, Yardim M, Aktun HL, et al. Serum and follicular fluid irisin levels in poor and high responder women undergoing IVF/ICSI. Eur Rev Med Pharmacol Sci 2016; 20:1940–6.
Ersahin A, Acet M, Ersahin SS, Acet T, Yardim M, Kenanoglu O, et al. Follicular Fluid Cerebellin and Betatrophin Regulate Metabolic Functions of Growing Follicles in PCOS. CERM 2017; 44:33–9.
Davoodi FG, Salsabili N, Sadeghipour Roodsari HR, Sattarian M. Effects of human follicular fluid and synthetic serum substitute on human embryonic development and cell cleavage. Acta Medica Iranica 2005; 43:1–6.
Jozwik M, Jozwik M, Teng C, Battaglia FC. Amino acid, ammonia and urea concentrations in human pre-ovulatory ovarian follicular fluid. Hum Reprod 2006; 21:2776–82.
Chang SCS, Jones JD, Ellefson RD, Ryan RJ. The porcine ovarian follicle: I. selected chemical analysis of follicular fluid at different developmental stages. Biol Reprod 1976; 15:321–8.
Wallace M, Cottell E, Gibney MJ, McAuliffe FM, Wingfield M, Brennan L. An investigation into the relationship between the metabolic profile of follicular fluid, oocyte developmental potential, and implantation outcome. Fertil Steril 2012; 97:1078-84.e1–e8.
Reinthaller A, Deutinger J, Riss P, Muller-Tyl E, Fischl F, Bieglmayer C, et al. Relationship between the steroid and prolactin concentration in follicular fluid and the maturation and fertilization of human oocytes. J In Vitro Fert Embryo Transf 1987; 4:228–31.
Artini PG, Battaglia C, D'Ambrogio G, Barreca A, Droghini F, Volpe A, et al. Relationship between human oocyte maturity, fertilization and follicularfluid growth factors. Hum Reprod 1994; 9:902–6.
Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, et al. The effect of follicular fluid reactive oxygen species on the outcomeof in vitro fertilization. Int J Fertil Womens Med 2000; 45:314–20.
Celik O, Aydin S, Celik N, Yilmaz M. Peptides: Basic determinants of reproductive functions. Peptides 2015; 72:34–43.
Carmina E, Orio F, Palomba S, Cascella T, Longo RA, Colao AM, et al. Evidence for altered adipocyte function in polycystic ovary syndrome. Eur J Endocrinol 2005; 152:389–94.
Panidis D, Kourtis A, Farmakiotis D, Mouslech T, Rousso D, Koliakos G. Serum adiponectin levels in women with polycystic ovary syndrome. Hum Reprod 2003; 18:1790–6.
Panidis D, Rousso D, Koliakos G, Kourtis A, Katsikis I, Farmakiotis D, et al. Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome. Fertil Steril 2006; 85:1778–83.
Celik O, Sahin I, Celik N, Hascalik S, Keskin L, Ozcan H, et al. Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study. Hum Reprod 2007; 22:2992–8.
Celik O, Celik N, Aydin S, Aygun BK, Haberal ET, Kuloglu T, et al. Ghrelin action on GnRH neurons and pituitary gonadotropes might be mediated by GnIH-GPR147 system. Horm Mol Biol Clin Investig 2016; 25:121–8.
Burcelin R, Thorens B, Glauser M, Gaillard RC, Pralong FP. Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin. Endocrinology 2003; 144:4484–91.
James S, Moralez J, Nagamani M. Increased secretion of amylin in women with polycystic ovary syndrome. Fertil Steril 2010; 94:211–5.
Jayasena CN, Abbara A, Veldhuis JD, Comninos AN, Ratnasabapathy R, De Silva A, et al. Increasing LH Pulsatility in Women With Hypothalamic Amenorrhoea Using Intravenous Infusion of Kisspeptin-54. J Clin Endocrinol Metab 2014; 99:E953–61.
Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Hum Reprod Update 2014; 20:485–500.
Dubuquoy C, Robichon C, Lasnier F, Langlois C, Dugail I, Foufelle F, et al. Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in Mouse and human hepatocytes. J Hepatol 2011; 55:145–53.
Li JZ, Huang Y, Karaman R, Ivanova PT, Brown HA, Roddy T, et al. Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. J Clin Invest 2012; 122:4130–44.
Rotterdam Eshre/Asrm-Sponsored Pcos Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81:19–25.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and Î²-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28:412–9.
Emekci Ozay O, Ozay AC, Acar B, Cagliyan E, Seçil M, Küme T. Role of kisspeptin in polycystic ovary syndrome (PCOS). Gynecol Endocrinol 2016; 32:718–22.
Buchanan CM, Phillips AR, Cooper GJ. Preptin derived from proinsulin-like growth factor II (proIGF-II) is secreted from pancreatic islet beta-cells and enhances insulin secretion. Biochem J 2001; 360:431–9.
Yang G, Li L, Chen W, Liu H, Boden G, Li K. Circulating preptin levels in normal, impaired glucose tolerance, and type 2 diabetic subjects. Ann Med 2009; 41:52–6.
Celik O, Celik N, Hascalik S, Sahin I, Aydin S, Ozerol E. An appraisal of serum preptin levels in PCOS. Fertil Steril 2011; 95:314–6.
Pirazzi C, Valenti L, Motta BM, Pingitore P, Hedfalk K, Mancina RM, et al. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells. Hum Mol Genet 2014; 23:4077–85.
Dubuquoy C, Burnol AF, Moldes M. PNPLA3, a genetic marker of progressive liver disease, still hiding its metabolic function? Clin Res Hepatol Gastroenterol 2013; 37:30–5.
Palmer CN, Maglio C, Pirazzi C, Burza MA, Adiels M, Burch L, et al. Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant. PLoSOne 2012; 7:e39362.
Lindholm A, Blomquist C, Bixo M, Dahlbom I, Hansson T, Sundström Poromaa I, et al. No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls. Hum Reprod 2011; 26:1478–85.
Villa J, Pratley RE. Adipose tissue dysfunction in polycystic ovary syndrome. Curr Diab Rep 2011; 11:179–84.
Yang F. Amylin in vasodilation, energy expenditure and inflammation. Front Biosci (Landmark Ed) 2014; 19:936–44.
James S, Moralez J, Nagamani M. Increased secretion of amylin in women with polycystic ovary syndrome. Fertil Steril 2010; 94:211–5.
Edwards RG. Follicular fluid. J Reprod Fertil 1974; 37:189–219.
Sutton ML, Gilchrist RB, Thompson JG. Effects of in-vivo and in-vitro environments on the metabolism of the cumulus-oocyte complex and its influence on oocyte developmental capacity. Hum Reprod 2003; 9:35–48.

References

Orsi NM, Gopichandran N, Leese HJ, Picton HM, Harris SE. Fluctuations in bovine ovarian follicular fluid composition throughout the oestrous cycle. Reprod 2005; 129:219–28.

Spitzer D, Murach KF, Lottspeich F, Staudach A, Illmensee K. Different protein patterns derived from follicular fluid of mature and immature human follicles. Hum Reprod 1996; 11:798–807.

Leroy JL, Vanholder T, Delanghe JR, Opsomer G, Van Soom A, Bols PE, et al. Metabolite and ionic composition of follicular fluid from different-sized follicles and their relationship to serum concentrations in dairy cows. Anim Reprod Sci 2004; 80:201–11.

Acet M, Celik N, Acet T, Ilhan S, Yardim M, Aktun HL, et al. Serum and follicular fluid irisin levels in poor and high responder women undergoing IVF/ICSI. Eur Rev Med Pharmacol Sci 2016; 20:1940–6.

Ersahin A, Acet M, Ersahin SS, Acet T, Yardim M, Kenanoglu O, et al. Follicular Fluid Cerebellin and Betatrophin Regulate Metabolic Functions of Growing Follicles in PCOS. CERM 2017; 44:33–9.

Davoodi FG, Salsabili N, Sadeghipour Roodsari HR, Sattarian M. Effects of human follicular fluid and synthetic serum substitute on human embryonic development and cell cleavage. Acta Medica Iranica 2005; 43:1–6.

Jozwik M, Jozwik M, Teng C, Battaglia FC. Amino acid, ammonia and urea concentrations in human pre-ovulatory ovarian follicular fluid. Hum Reprod 2006; 21:2776–82.

Chang SCS, Jones JD, Ellefson RD, Ryan RJ. The porcine ovarian follicle: I. selected chemical analysis of follicular fluid at different developmental stages. Biol Reprod 1976; 15:321–8.

Wallace M, Cottell E, Gibney MJ, McAuliffe FM, Wingfield M, Brennan L. An investigation into the relationship between the metabolic profile of follicular fluid, oocyte developmental potential, and implantation outcome. Fertil Steril 2012; 97:1078-84.e1–e8.

Reinthaller A, Deutinger J, Riss P, Muller-Tyl E, Fischl F, Bieglmayer C, et al. Relationship between the steroid and prolactin concentration in follicular fluid and the maturation and fertilization of human oocytes. J In Vitro Fert Embryo Transf 1987; 4:228–31.

Artini PG, Battaglia C, D'Ambrogio G, Barreca A, Droghini F, Volpe A, et al. Relationship between human oocyte maturity, fertilization and follicularfluid growth factors. Hum Reprod 1994; 9:902–6.

Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, et al. The effect of follicular fluid reactive oxygen species on the outcomeof in vitro fertilization. Int J Fertil Womens Med 2000; 45:314–20.

Celik O, Aydin S, Celik N, Yilmaz M. Peptides: Basic determinants of reproductive functions. Peptides 2015; 72:34–43.

Carmina E, Orio F, Palomba S, Cascella T, Longo RA, Colao AM, et al. Evidence for altered adipocyte function in polycystic ovary syndrome. Eur J Endocrinol 2005; 152:389–94.

Panidis D, Kourtis A, Farmakiotis D, Mouslech T, Rousso D, Koliakos G. Serum adiponectin levels in women with polycystic ovary syndrome. Hum Reprod 2003; 18:1790–6.

Panidis D, Rousso D, Koliakos G, Kourtis A, Katsikis I, Farmakiotis D, et al. Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome. Fertil Steril 2006; 85:1778–83.

Celik O, Sahin I, Celik N, Hascalik S, Keskin L, Ozcan H, et al. Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study. Hum Reprod 2007; 22:2992–8.

Celik O, Celik N, Aydin S, Aygun BK, Haberal ET, Kuloglu T, et al. Ghrelin action on GnRH neurons and pituitary gonadotropes might be mediated by GnIH-GPR147 system. Horm Mol Biol Clin Investig 2016; 25:121–8.

Burcelin R, Thorens B, Glauser M, Gaillard RC, Pralong FP. Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin. Endocrinology 2003; 144:4484–91.

James S, Moralez J, Nagamani M. Increased secretion of amylin in women with polycystic ovary syndrome. Fertil Steril 2010; 94:211–5.

Jayasena CN, Abbara A, Veldhuis JD, Comninos AN, Ratnasabapathy R, De Silva A, et al. Increasing LH Pulsatility in Women With Hypothalamic Amenorrhoea Using Intravenous Infusion of Kisspeptin-54. J Clin Endocrinol Metab 2014; 99:E953–61.

Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Hum Reprod Update 2014; 20:485–500.

Dubuquoy C, Robichon C, Lasnier F, Langlois C, Dugail I, Foufelle F, et al. Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in Mouse and human hepatocytes. J Hepatol 2011; 55:145–53.

Li JZ, Huang Y, Karaman R, Ivanova PT, Brown HA, Roddy T, et al. Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. J Clin Invest 2012; 122:4130–44.

Rotterdam Eshre/Asrm-Sponsored Pcos Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81:19–25.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and Î²-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28:412–9.

Emekci Ozay O, Ozay AC, Acar B, Cagliyan E, Seçil M, Küme T. Role of kisspeptin in polycystic ovary syndrome (PCOS). Gynecol Endocrinol 2016; 32:718–22.

Buchanan CM, Phillips AR, Cooper GJ. Preptin derived from proinsulin-like growth factor II (proIGF-II) is secreted from pancreatic islet beta-cells and enhances insulin secretion. Biochem J 2001; 360:431–9.

Yang G, Li L, Chen W, Liu H, Boden G, Li K. Circulating preptin levels in normal, impaired glucose tolerance, and type 2 diabetic subjects. Ann Med 2009; 41:52–6.

Celik O, Celik N, Hascalik S, Sahin I, Aydin S, Ozerol E. An appraisal of serum preptin levels in PCOS. Fertil Steril 2011; 95:314–6.

Pirazzi C, Valenti L, Motta BM, Pingitore P, Hedfalk K, Mancina RM, et al. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells. Hum Mol Genet 2014; 23:4077–85.

Dubuquoy C, Burnol AF, Moldes M. PNPLA3, a genetic marker of progressive liver disease, still hiding its metabolic function? Clin Res Hepatol Gastroenterol 2013; 37:30–5.

Palmer CN, Maglio C, Pirazzi C, Burza MA, Adiels M, Burch L, et al. Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant. PLoSOne 2012; 7:e39362.

Lindholm A, Blomquist C, Bixo M, Dahlbom I, Hansson T, Sundström Poromaa I, et al. No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls. Hum Reprod 2011; 26:1478–85.

Villa J, Pratley RE. Adipose tissue dysfunction in polycystic ovary syndrome. Curr Diab Rep 2011; 11:179–84.

Yang F. Amylin in vasodilation, energy expenditure and inflammation. Front Biosci (Landmark Ed) 2014; 19:936–44.

James S, Moralez J, Nagamani M. Increased secretion of amylin in women with polycystic ovary syndrome. Fertil Steril 2010; 94:211–5.

Edwards RG. Follicular fluid. J Reprod Fertil 1974; 37:189–219.

Sutton ML, Gilchrist RB, Thompson JG. Effects of in-vivo and in-vitro environments on the metabolism of the cumulus-oocyte complex and its influence on oocyte developmental capacity. Hum Reprod 2003; 9:35–48.