Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients

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  • 1 Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • | 2 Center for Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • | 3 Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
  • | 4 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
  • | 5 School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • | 6 Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China

Correspondence should be addressed to S Li or R Huang; Email: rj_shengxianli@163.com or huangrong@renji.com

*(Y Feng and J Qi contributed equally to this work)

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In Brief

Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility in women. This study identified changes in free fatty acids profiles in the follicular fluid that may lead to better diagnosis and management of infertility in PCOS women.

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous disease characterized by various endocrine/metabolic disorders and impaired reproductive potential. Alterations in oocyte competence are considered potentially causative factors for infertility in PCOS women and analyzing the composition of follicular fluid in these patients may help to identify which changes have the potential to alter oocyte quality. In this study, free fatty acid metabolic signatures in follicular fluid were performed to identify changes that may impact oocyte competence in non-obese PCOS women. Sixty-four non-obese women (32 with PCOS and 32 age- and BMI-matched controls) undergoing in vitro fertilization were recruited. Embryo quality was morphologically assessed. Free fatty acid metabolic profiling in follicular fluid was performed using gas/liquid chromatography-mass spectrometry. Principal component analysis and orthogonal partial least squares-discriminant analysis models were further constructed. Nine free fatty acids and 24 eicosanoids were identified and several eicosanoids synthesized by the cyclooxygenase pathway were significantly elevated in PCOS patients compared to controls. The combination of PGE2, PGF2α, PGJ2, and TXB2 had an area under the curve of 0.867 (0.775–0.960) for PCOS discrimination. Furthermore, follicular fluid levels of PGE2 and PGJ2 were negatively correlated with high-quality embryo rate in PCOS patients (P < 0.05). Metabolomic analysis revealed that follicular fluid lipidomic profiles undergo changes in non-obese PCOS women, which suggests that identifying changes in important metabolic signatures may give us a better understanding of the pathogenesis of PCOS. Furthermore, elevated PGE2 and PGJ2 concentrations may contribute to impaired oocyte competence in non-obese PCOS patients.

Supplementary Materials

 

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  • Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES & Yildiz BO 2004 The prevalence and features of the polycystic ovary syndrome in an unselected population. Journal of Clinical Endocrinology and Metabolism 89 27452749. (https://doi.org/10.1210/jc.2003-032046)

    • Search Google Scholar
    • Export Citation
  • Berisha B, Rodler D, Schams D, Sinowatz F & Pfaffl MW 2019 Prostaglandins in superovulation induced bovine follicles during the preovulatory period and early corpus luteum. Frontiers in Endocrinology 10 467. (https://doi.org/10.3389/fendo.2019.00467)

    • Search Google Scholar
    • Export Citation
  • Boruszewska D, Kowalczyk-Zieba I, Suwik K, Staszkiewicz-Chodor J, Jaworska J, Lukaszuk K & Woclawek-Potocka I 2020 Prostaglandin E(2) affects in vitro maturation of bovine oocytes. Reproductive Biology and Endocrinology 18 40. (https://doi.org/10.1186/s12958-020-00598-9)

    • Search Google Scholar
    • Export Citation
  • Buczynski MW, Dumlao DS & Dennis EA 2009 Thematic review series: proteomics. an integrated omics analysis of eicosanoid biology thematic review series. Journal of Lipid Research 50 10151038. (https://doi.org/10.1194/jlr.R900004-JLR200)

    • Search Google Scholar
    • Export Citation
  • Ciepiela P, Bączkowski T, Drozd A, Kazienko A, Stachowska E & Kurzawa R 2015 Arachidonic and linoleic acid derivatives impact oocyte ICSI fertilization-a prospective analysis of follicular fluid and a matched oocyte in a ‘one follicle-one retrieved oocyte-one resulting embryo’ investigational setting. PLoS ONE 10 e0119087. (https://doi.org/10.1371/journal.pone.0119087)

    • Search Google Scholar
    • Export Citation
  • Duffy DM, Ko C, Jo M, Brannstrom M & Curry TE 2019 Ovulation: parallels with inflammatory processes. Endocrine Reviews 40 369416. (https://doi.org/10.1210/er.2018-00075)

    • Search Google Scholar
    • Export Citation
  • González F, Nair KS, Daniels JK, Basal E & Schimke JM 2012 Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women. American Journal of Physiology: Endocrinology and Metabolism 302 E297E306. (https://doi.org/10.1152/ajpendo.00416.2011)

    • Search Google Scholar
    • Export Citation
  • Han X, Yang K, Cheng H, Fikes KN & Gross RW 2005 Shotgun lipidomics of phosphoethanolamine-containing lipids in biological samples after one-step in situ derivatization. Journal of Lipid Research 46 15481560. (https://doi.org/10.1194/jlr.D500007-JLR200)

    • Search Google Scholar
    • Export Citation
  • Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS & Fauser BC 2006 A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Human Reproduction Update 12 1321. (https://doi.org/10.1093/humupd/dmi036)

    • Search Google Scholar
    • Export Citation
  • Huang R, Xue X, Li S, Wang Y, Sun Y, Liu W, Yin H & Tao T 2018 Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats. Journal of Cellular and Molecular Medicine 22 33883396. (https://doi.org/10.1111/jcmm.13614)

    • Search Google Scholar
    • Export Citation
  • Jungheim ES, Macones GA, Odem RR, Patterson BW, Lanzendorf SE, Ratts VS & Moley KH 2011 Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertility and Sterility 95 19701974. (https://doi.org/10.1016/j.fertnstert.2011.01.154)

    • Search Google Scholar
    • Export Citation
  • Kikut J, Komorniak N, Ziętek M, Palma J & Szczuko M 2020 Inflammation with the participation of arachidonic (AA) and linoleic acid (LA) derivatives (HETEs and HODEs) is necessary in the course of a normal reproductive cycle and pregnancy. Journal of Reproductive Immunology 141 103177. (https://doi.org/10.1016/j.jri.2020.103177)

    • Search Google Scholar
    • Export Citation
  • Li S, Chu Q, Ma J, Sun Y, Tao T, Huang R, Liao Y, Yue J, Zheng J & Wang L et al.2017 Discovery of novel lipid profiles in PCOS: do insulin and androgen oppositely regulate bioactive lipid production? Journal of Clinical Endocrinology and Metabolism 102 810821. (https://doi.org/10.1210/jc.2016-2692)

    • Search Google Scholar
    • Export Citation
  • Li S, Qi J, Tao Y, Zhu Q, Huang R, Liao Y, Yue J, Liu W, Zhao H & Yin H et al.2020 Elevated levels of arachidonic acid metabolites in follicular fluid of PCOS patients. Reproduction 159 159169. (https://doi.org/10.1530/REP-19-0136)

    • Search Google Scholar
    • Export Citation
  • Liang C, Zhang X, Qi C, Hu H, Zhang Q, Zhu X & Fu Y 2021 UHPLC-MS-MS analysis of oxylipins metabolomics components of follicular fluid in infertile individuals with diminished ovarian reserve. Reproductive Biology and Endocrinology 19 143. (https://doi.org/10.1186/s12958-021-00825-x)

    • Search Google Scholar
    • Export Citation
  • Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM & Dey SK 1997 Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91 197208. (https://doi.org/10.1016/s0092-8674(0080402-x)

    • Search Google Scholar
    • Export Citation
  • Marei WF, Abayasekara DR, Wathes DC & Fouladi-Nashta AA 2014 Role of PTGS2-generated PGE2 during gonadotrophin-induced bovine oocyte maturation and cumulus cell expansion. Reproductive Biomedicine Online 28 388400. (https://doi.org/10.1016/j.rbmo.2013.11.005)

    • Search Google Scholar
    • Export Citation
  • Nagy B, Poto L, Farkas N, Koppan M, Varnagy A, Kovacs K, Papp S, Bohonyi N & Bodis J 2019 Follicular fluid progesterone concentration is associated with fertilization outcome after IVF: a systematic review and meta-analysis. Reproductive Biomedicine Online 38 871882. (https://doi.org/10.1016/j.rbmo.2018.12.045)

    • Search Google Scholar
    • Export Citation
  • Niringiyumukiza JD, Cai H & Xiang W 2018 Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation. Reproductive Biology and Endocrinology 16 43. (https://doi.org/10.1186/s12958-018-0359-5)

    • Search Google Scholar
    • Export Citation
  • Niu Z, Lin N, Gu R, Sun Y & Feng Y 2014 Associations between insulin resistance, free fatty acids, and oocyte quality in polycystic ovary syndrome during in vitro fertilization. Journal of Clinical Endocrinology and Metabolism 99 E2269E2276. (https://doi.org/10.1210/jc.2013-3942)

    • Search Google Scholar
    • Export Citation
  • Palomba S, Falbo A, Russo T, Tolino A, Orio F & Zullo F 2010 Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes. Fertility and Sterility 94 18051811. (https://doi.org/10.1016/j.fertnstert.2009.10.043)

    • Search Google Scholar
    • Export Citation
  • Palomba S, Daolio J & La Sala GB 2017 Oocyte Competence in women with polycystic ovary syndrome. Trends in Endocrinology and Metabolism 28 186198. (https://doi.org/10.1016/j.tem.2016.11.008)

    • Search Google Scholar
    • Export Citation
  • Pereira de Moraes F, Amaral D’Avila C, Caetano de Oliveira F, Ávila de Castro N, Diniz Vieira A, Schneider A, Machado Pfeifer LF, Cantarelli Pegoraro LM, Ferreira R & Germano Ferst J et al.2021 Prostaglandin F2α regulation and function during ovulation and luteinization in cows. Theriogenology 171 3037. (https://doi.org/10.1016/j.theriogenology.2021.05.008)

    • Search Google Scholar
    • Export Citation
  • Perovic MD, Sudar-Milovanovic EM, Simonovic ED, Resanovic IM, Draganic VD, Radakovic JD, Soldatovic IA & Isenovic ER 2019 Hypothesis regarding the effects of gonadotropins on the level of free fatty acids and phospholipids in serum and follicular fluid during controlled ovarian stimulation. Medical Hypotheses 123 3034. (https://doi.org/10.1016/j.mehy.2018.11.021)

    • Search Google Scholar
    • Export Citation
  • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility and Sterility 81 1925. (https://doi.org/10.1016/j.fertnstert.2003.10.004)

    • Search Google Scholar
    • Export Citation
  • Rajska A, Buszewska-Forajta M, Rachoń D & Markuszewski MJ 2020 Metabolomic insight into polycystic ovary syndrome – an overview. International Journal of Molecular Sciences 21 4853. (https://doi.org/10.3390/ijms21144853)

    • Search Google Scholar
    • Export Citation
  • Ruiz-Sanz JI, Pérez-Ruiz I, Meijide S, Ferrando M, Larreategui Z & Ruiz-Larrea MB 2019 Lower follicular n-3 polyunsaturated fatty acid levels are associated with a better response to ovarian stimulation. Journal of Assisted Reproduction and Genetics 36 473482. (https://doi.org/10.1007/s10815-018-1384-1)

    • Search Google Scholar
    • Export Citation
  • Scott L, Alvero R, Leondires M & Miller B 2000 The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Human Reproduction 15 23942403. (https://doi.org/10.1093/humrep/15.11.2394)

    • Search Google Scholar
    • Export Citation
  • Sharma AK & Sharma RK 2020 Effect of prostaglandins E(2) and F(2α) on granulosa cell apoptosis in goat ovarian follicles. Iranian Journal of Veterinary Research 21 97102. (https://doi.org/10.22099/ijvr.2020.35165.5175)

    • Search Google Scholar
    • Export Citation
  • Shorakae S, Teede H, de Courten B, Lambert G, Boyle J & Moran LJ 2015 The emerging role of chronic low-grade inflammation in the pathophysiology of polycystic ovary syndrome. Seminars in Reproductive Medicine 33 257269. (https://doi.org/10.1055/s-0035-1556568)

    • Search Google Scholar
    • Export Citation
  • Snider AP & Wood JR 2019 Obesity induces ovarian inflammation and reduces oocyte quality. Reproduction 158 R79R90. (https://doi.org/10.1530/REP-18-0583)

    • Search Google Scholar
    • Export Citation
  • Soares de Carvalho JG, Tonizza de Carvalho NA, Souza DC, Martins Júnior B, Macedo GG, Vieira LM, Sales JNS, Ghuman SS, D'Occhio MJ & Baruselli PS 2020 Administration of PGF(2α) during the periovulatory period increased fertilization rate in superovulated buffaloes. Theriogenology 145 138143. (https://doi.org/10.1016/j.theriogenology.2019.11.010)

    • Search Google Scholar
    • Export Citation
  • Spritzer PM, Lecke SB, Satler F & Morsch DM 2015 Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome. Reproduction 149 R219R227. (https://doi.org/10.1530/REP-14-0435)

    • Search Google Scholar
    • Export Citation
  • Takahashi T, Morrow JD, Wang H & Dey SK 2006 Cyclooxygenase-2-derived prostaglandin E(2) directs oocyte maturation by differentially influencing multiple signaling pathways. Journal of Biological Chemistry 281 3711737129. (https://doi.org/10.1074/jbc.M608202200)

    • Search Google Scholar
    • Export Citation
  • Wang J, Shen XX, Huang XH & Zhao ZM 2012 Follicular fluid levels of prostaglandin E2 and the effect of prostaglandin E2 on steroidogenesis in granulosa-lutein cells in women with moderate and severe endometriosis undergoing in vitro fertilization and embryo transfer. Chinese Medical Journal 125 39853990. (https://doi.org/10.3760/cma.j.issn.0366-6999.2012.22.014)

    • Search Google Scholar
    • Export Citation
  • Xu X, Du C, Zheng Q, Peng L & Sun Y 2014 Effect of metformin on serum interleukin-6 levels in polycystic ovary syndrome: a systematic review. BMC Women’s Health 14 93. (https://doi.org/10.1186/1472-6874-14-93)

    • Search Google Scholar
    • Export Citation
  • Yang J, Schmelzer K, Georgi K & Hammock BD 2009 Quantitative profiling method for oxylipin metabolome by liquid chromatography electrospray ionization tandem mass spectrometry. Analytical Chemistry 81 80858093. (https://doi.org/10.1021/ac901282n)

    • Search Google Scholar
    • Export Citation
  • Yazawa T, Kawabe S, Kanno M, Mizutani T, Imamichi Y, Ju Y, Matsumura T, Yamazaki Y, Usami Y & Kuribayashi M et al.2013 Androgen/androgen receptor pathway regulates expression of the genes for cyclooxygenase-2 and amphiregulin in periovulatory granulosa cells. Molecular and Cellular Endocrinology 369 4251. (https://doi.org/10.1016/j.mce.2013.02.004)

    • Search Google Scholar
    • Export Citation
  • Yu DX, Sun Q, Ye XW, Pan A, Zong G, Zhou YH, Li HX, Hu FB & Lin X 2012 Erythrocyte trans-fatty acids, type 2 diabetes and cardiovascular risk factors in middle-aged and older Chinese individuals. Diabetologia 55 29542962. (https://doi.org/10.1007/s00125-012-2674-2)

    • Search Google Scholar
    • Export Citation
  • Zhao Y, Fu L, Li R, Wang LN, Yang Y, Liu NN, Zhang CM, Wang Y, Liu P & Tu BB et al.2012 Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis. BMC Medicine 10 153. (https://doi.org/10.1186/1741-7015-10-153)

    • Search Google Scholar
    • Export Citation
  • Zhao X, Xu F, Qi B, Hao S, Li Y, Li Y, Zou L, Lu C, Xu G & Hou L 2014 Serum metabolomics study of polycystic ovary syndrome based on liquid chromatography-mass spectrometry. Journal of Proteome Research 13 11011111. (https://doi.org/10.1021/pr401130w)

    • Search Google Scholar
    • Export Citation
  • Zhu Q, Zuo R, He Y, Wang Y, Chen ZJ, Sun Y & Sun K 2016 Local regeneration of cortisol by 11β-HSD1 contributes to insulin resistance of the granulosa cells in PCOS. Journal of Clinical Endocrinology and Metabolism 101 21682177. (https://doi.org/10.1210/jc.2015-3899)

    • Search Google Scholar
    • Export Citation