Fatty Acids in Subcutaneous Adipose Tissue of Pregnant Women with and without Polycystic Ovary Syndrome Are Associated with Genes Related to Steroidogenesis: A Case-Control Study

Document Type : Original Article


1 Department of Biology, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

3 Breast Disease Research Center (BDRC), Tehran University of Medical Sciences, Tehran, Iran

4 Department of Gynecology and Obstetrics, Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Animal and Poultry Science, College of Aburaihan, University of Tehran, Tehran, Iran

6 Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

7 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

8 Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran

9 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

10 Gyn-medicum, Center for Reproductive Medicine, GÖttingen, Germany


Background: The qualitative analysis of adipose tissue (AT) is an exciting area for research and clinical applications in several diseases and it is emerging along with the quantitative approach to research on overweight and obese people. While the importance of steroid metabolism in women with polycystic ovary syndrome (PCOS) has been reported, limited data exists on the effective roles of AT in pregnant women suffering from PCOS. The aim of this study was to determine association of fatty acid (FA) profiles with expression of 14 steroid genes in abdominal subcutaneous AT of PCOS vs. non-PCOS pregnant women.
Materials and Methods: In this case-control study, the AT samples of 36 non-PCOS pregnant women and 12 pregnant women with PCOS (3:1 ratio control: case) who underwent cesarean section were collected. Relationship of expressing gene targets and different features were performed using Pearson correlation analysis on the R 3.6.2 software. The ggplot2 package in R tool was used to draw the plots.
Results: Age (31.4 and 31.5 years, P=0.99), body mass index (BMI) (prior pregnancy 26 and 26.5 kg.m-2, P=0.62) and at delivery day (30.1 and 31, P=0.94), gestational period (264 and 267 days, P=0.70) and parity (1.4 and 1.4, P=0.42) of non-PCOS and PCOS pregnant women were similar. Expression of steroidogenic acute regulator (STAR) and 11β-Hydroxysteroid dehydrogenase (11BHSD2) in non-PCOS pregnant women showed the highest association with eicosapentaenoic acid (EPA, C20:5 n-3, r=0.59, P=0.001) and (r=0.66, P=0.001), respectively. In the all participants, STAR mRNA level showed the greatest association with the EPA fatty acid concentration (P=0.001, r=0.51).
Conclusion: Our results showed a link between the genes involved in steroid metabolism and fatty acids in AT of pregnant women, especially for omega-3 FA and the gene involved in the first step of steroidogenesis in subcutaneous AT. These findings warrant further studies.


  1. Guzik TJ, Mangalat D, Korbut R. Adipocytokines - novel link between inflammation and vascular function? J Physiol Pharmacol. 2006; 57(4): 505-528.
  2. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009; 91(2): 456-488.
  3. Abruzzese GA, Silva AF, Velazquez ME, Ferrer MJ, Motta AB. Hyperandrogenism and Polycystic ovary syndrome: Effects in pregnancy and offspring development. WIREs Mech Dis. 2022; 14(5): e1558.
  4. Vara Prasad SS, Jeya Kumar SS, Kumar PU, Qadri SS, Vajreswari A. Dietary fatty acid composition alters 11β-hydroxysteroid dehydrogenase type 1 gene expression in rat retroperitoneal white adipose tissue. Lipids Health Dis. 2010; 9: 111.
  5. Petrus P, Rosqvist F, Edholm D, Mejhert N, Arner P, Dahlman I, et al. Saturated fatty acids in human visceral adipose tissue are associated with increased 11- β-hydroxysteroid-dehydrogenase type 1 expression. Lipids Health Dis. 2015; 14: 42.
  6. Li J, Papadopoulos V, Vihma V. Steroid biosynthesis in adipose tissue. Steroids. 2015; 103: 89-104.
  7. Emami N, Moini A, Yaghmaei P, Akbarinejad V, Shahhoseini M, Alizadeh A. Differences in expression of genes related to steroidgenesis in abdominal subcutaneous adipose tissue of pregnant women with and without PCOS; a case control study. BMC Pregnancy Childbirth. 2021; 21(1): 490.
  8. García-López S, Villanueva Arriaga RE, Nájera Medina O, Rodríguez López CP, Figueroa-Valverde L, Cervera EG, et al. One month of omega-3 fatty acid supplementation improves lipid profiles, glucose levels and blood pressure in overweight schoolchildren with metabolic syndrome. J Pediatr Endocrinol Metab. 2016; 29(10): 1143-1150.
  9. Mehendale SS, Kilari Bams AS, Deshmukh CS, Dhorepatil BS, Nimbargi VN, Joshi SR. Oxidative stress-mediated essential polyunsaturated fatty acid alterations in female infertility. Hum Fertil (Camb). 2009; 12(1): 28-33.
  10. Mohammadi E, Rafraf M. Benefits of omega-3 Fatty acids supplementation on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Health Promot Perspect. 2012; 2(2): 197-204.
  11. Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, et al. SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 1993; 75(1): 187-197.
  12. Göttlicher M, Widmark E, Li Q, Gustafsson JA. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci USA. 1992; 89(10): 4653-4657.
  13. Jump DB. Fatty acid regulation of gene transcription. Crit Rev Clin Lab Sci. 2004; 41(1): 41-78.
  14. Emami N, Alizadeh A, Moini A, Yaghmaei P, Shahhosseini M. Differences in fatty acid profiles and desaturation indices of abdominal subcutaneous adipose tissue between pregnant women with and without PCOS. Adipocyte. 2020; 9(1): 16-23.
  15. Yang K, Zeng L, Bao T, Ge J. Effectiveness of Omega-3 fatty acid for polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2018; 16(1): 27
  16. Hajishafiee M, Askari G, Iranj B, Ghiasvand R, Bellissimo N, Totosy de Zepetnek J, et al. The Effect of n-3 polyunsaturated fatty acid supplementation on androgen status in patients with polycystic ovary syndrome: a systematic review and meta-analysis of clinical trials. Horm Metab Res. 2016; 48(5): 281-289.
  17. Lindroos J, Husa J, Mitterer G, Haschemi A, Rauscher S, Haas R, et al. Human but not mouse adipogenesis is critically dependent on LMO3. Cell Metab. 2013; 18(1): 62-74.
  18. Legrand-Poels S, Esser N, L'Homme L, Scheen A, Paquot N, Piette J. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes. Biochem Pharmacol. 2014; 92(1): 131-141.
    19. De Boer AA, Monk JM, Liddle DM, Hutchinson AL, Power KA, Ma DW, et al. Fish-oil-derived n-3 polyunsaturated fatty acids reduce NLRP3 inflammasome activity and obesity-related inflammatory cross-talk between adipocytes and CD11b(+) macrophages. J Nutr Biochem. 2016; 34: 61-72.
    20. Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2015; 1851(4): 469-484.
    21. Hu X, Weng X, Tian Y, Wang C, Yang Y, Xu K, et al. Effects of omega-3 polyunsaturated fatty acids on steroidogenesis and cellular development in PCOS rats. Food Funct. 2019; 10(5): 2504-2514.
    22. Haghiac M, Yang XH, Presley L, Smith S, Dettelback S, Minium J, et al. Dietary omega-3 fatty acid supplementation reduces inflammation in obese pregnant women: a randomized double-blind controlled clinical trial. PLoS One. 2015; 10(9): e0137309.
    23. Mansoori A, Sotoudeh G, Djalali M, Eshraghian MR, Keramatipour M, Nasli-Esfahani E, et al. Effect of DHA-rich fish oil on PPARγ target genes related to lipid metabolism in type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial. J Clin Lipidol. 2015; 9(6): 770-777.
    24. Lee KR, Midgette Y, Shah R. Fish oil derived omega 3 fatty acids suppress adipose NLRP3 inflammasome signaling in human obesity. J Endocr Soc. 2018; 3(3): 504-515.
    25. Forouhi N, Shab-Bidar S, Djafarian K. Effect of omega-3 fatty acids supplementation on testosterone levels in women with polycystic ovary syndrome: Meta-analysis of randomized controlled trials. JNSD. 2015: 1(3): 165-170.
    26. Nadjarzadeh A, Dehghani Firouzabadi R, Vaziri N, Daneshbodi H, Lotfi MH, Mozaffari-Khosravi H. The effect of omega-3 supplementation on androgen profile and menstrual status in women with polycystic ovary syndrome: a randomized clinical trial. Iran J Reprod Med. 2013; 11(8): 665-672.
    27. Ma X, Weng X, Hu X, Wang Q, Tian Y, Ding Y, et al. Roles of different n-3/n-6 PUFA ratios in ovarian cell development and steroidogenesis in PCOS rats. Food Funct. 2019; 10(11): 7397-7406.
    28. Emam SR, Abd-Elsalam RM, Azouz AA, Ali SE, El Badawy SA, Ibrahim MA, et al. Linum usitatissimum seeds oil down-regulates mRNA expression for the steroidogenic acute regulatory protein and Cyp11A1 genes, ameliorating letrezole-induced polycystic ovarian syndrome in a rat model. J Physiol Pharmacol. 2021; 72(1).