Serum progranulin levels are elevated in infertile women with obesity
Abstract
Introduction: The aim of the present study was to investigate the changes in serum progranulin and sex hormone levels in infertile women with obesity. Material and methods: A total of 171 infertile women who had fertility desire were included in this cross-sectional study. The initial assessment included measurements of weight, height, waist circumference, and hip circumference to calculate body mass index (BMI) and waist/hip ratio. All participants were categorised into two groups in accordance with BMI as a control group ( < 30 kg/m2, n = 135) and a study group (≥ 30 kg/m2, n = 36). After anthropometric measurements, venous blood samples were taken for analyses of oestradiol and follicle stimulating hormone (FSH), luteinising hormone, total testosterone (TT), 17-hydroxyprogesterone, dehydroepiandrosterone sulphate, anti-Müllerian hormone, and progranulin. Results: The present study demonstrated that the overweight women had higher FSH levels (p < 0.01). Elevated TT levels were detected in obese women (p < 0.05). Progranulin concentrations were higher in the study group than in the control group (p < 0.05). Regression analysis demonstrated that there was a relationship between the serum progranulin concentrations and BMI (p < 0.05). Conclusions: Our findings support that the elevated progranulin levels are associated with obesity in infertile women. Therefore, infertile and obese patients may benefit if their serum progranulin levels decrease. Further studies are needed to elucidate this issue.
Keywords: progranulingranulinobesityinfertility
References
- Anakwe OO, Gerton GL. Acrosome biogenesis begins during meiosis: evidence from the synthesis and distribution of an acrosomal glycoprotein, acrogranin, during guinea pig spermatogenesis. Biol Reprod. 1990; 42(2): 317–328.
- Daniel R, Daniels E, He Z, et al. Progranulin (acrogranin/PC cell-derived growth factor/granulin-epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development. Dev Dyn. 2003; 227(4): 593–599.
- Bateman A, Bennett HPJ. The granulin gene family: from cancer to dementia. Bioessays. 2009; 31(11): 1245–1254.
- Bateman A, Bennett HP. Granulins: the structure and function of an emerging family of growth factors. J Endocrinol. 1998; 158(2): 145–151.
- Koo DH, Park CY, Lee ES, et al. Progranulin as a prognostic biomarker for breast cancer recurrence in patients who had hormone receptor-positive tumors: a cohort study. PLoS One. 2012; 7(6): e39880.
- Han JJ, Yu M, Houston N, et al. Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers. Gynecol Oncol. 2011; 120(1): 5–10.
- Lu Yi, Zheng L, Zhang W, et al. Growth factor progranulin contributes to cervical cancer cell proliferation and transformation in vivo and in vitro. Gynecol Oncol. 2014; 134(2): 364–371.
- Demorrow S. Progranulin: a novel regulator of gastrointestinal cancer progression. Transl Gastrointest Cancer. 2013; 2(3): 145–151.
- Donald CD, Laddu A, Chandham P, et al. Expression of progranulin and the epithelin/granulin precursor acrogranin correlates with neoplastic state in renal epithelium. Anticancer Res. 2001; 21(6A): 3739–3742.
- Finch N, Baker M, Crook R, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain. 2009; 132(Pt 3): 583–591.
- Tang W, Lu Yi, Tian QY, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011; 332(6028): 478–484.
- Guerra RR, Kriazhev L, Hernandez-Blazquez FJ, et al. Progranulin is a stress-response factor in fibroblasts subjected to hypoxia and acidosis. Growth Factors. 2007; 25(4): 280–285.
- Zhu J, Nathan C, Jin W, et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2002; 111(6): 867–878.
- Kessenbrock K, Fröhlich L, Sixt M, et al. Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. J Clin Invest. 2008; 118(7): 2438–2447.
- Eriksen JL, Mackenzie IRA. Progranulin: normal function and role in neurodegeneration. J Neurochem. 2008; 104(2): 287–297.
- Gundogan K, Bayram F, Gedik V, et al. Metabolic syndrome prevalence according to ATP III and IDF criteria and related factors in Turkish adults. Arch Med Sci. 2013; 9(2): 243–253.
- Satman I, Omer B, Tutuncu Y, et al. TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013; 28(2): 169–180.
- Obesity: preventing and managing the global epidemic. World Health Organization, Geneva 2000.
- Marshall NE, Spong CY. Obesity, pregnancy complications, and birth outcomes. Semin Reprod Med. 2012; 30(6): 465–471.
- Inal HA, Yilmaz N, Gorkem U, et al. The impact of follicular fluid adiponectin and ghrelin levels based on BMI on IVF outcomes in PCOS. J Endocrinol Invest. 2016; 39(4): 431–437.
- Rittenberg V, Seshadri S, Sunkara SK, et al. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online. 2011; 23(4): 421–439.
- Yoo H, Hwang S, Hong H, et al. Implication of Progranulin and C1q/TNF-Related Protein-3 (CTRP3) on Inflammation and Atherosclerosis in Subjects with or without Metabolic Syndrome. PLoS ONE. 2013; 8(2): e55744.
- Matsubara T, Mita A, Minami K, et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab. 2012; 15(1): 38–50.
- Qu H, Deng H, Hu Z. Plasma Progranulin Concentrations Are Increased in Patients with Type 2 Diabetes and Obesity and Correlated with Insulin Resistance. Mediators Inflamm. 2013; 2013: 1–6.
- Yoo H, Hwang S, Hong H, et al. Implication of Progranulin and C1q/TNF-Related Protein-3 (CTRP3) on Inflammation and Atherosclerosis in Subjects with or without Metabolic Syndrome. PLoS ONE. 2013; 8(2): e55744.
- Klöting N, Fasshauer M, Dietrich A, et al. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010; 299(3): E506–E515.
- Nicoletto B, Canani L. The role of progranulin in diabetes and kidney disease. Diabetol Metab Syndr. 2015; 7(1): 117.
- Li H, Zhou Bo, Xu L, et al. Circulating PGRN is significantly associated with systemic insulin sensitivity and autophagic activity in metabolic syndrome. Endocrinology. 2014; 155(9): 3493–3507.
- Waki H, Tontonoz P. Endocrine Functions of Adipose Tissue. Annu Rev Pathol. 2007; 2(1): 31–56.
- Nguyen AD, Nguyen TA, Martens LH, et al. Progranulin: at the interface of neurodegenerative and metabolic diseases. Trends Endocrinol Metab. 2013; 24(12): 597–606.
- Cao Y. Angiogenesis modulates adipogenesis and obesity. J Clin Invest. 2007; 117(9): 2362–2368.
- Toh H, Cao M, Daniels E, et al. Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model. PLoS One. 2013; 8(5): e64989.
- Kim HK, Shin MS, Youn BS, et al. Involvement of progranulin in hypothalamic glucose sensing and feeding regulation. Endocrinology. 2011; 152(12): 4672–4682.
- Egashira Y, Suzuki Y, Azuma Y, et al. The growth factor progranulin attenuates neuronal injury induced by cerebral ischemia-reperfusion through the suppression of neutrophil recruitment. J Neuroinflammation. 2013; 10: 105.
- Kanazawa M, Kawamura K, Takahashi T, et al. Multiple therapeutic effects of progranulin on experimental acute ischaemic stroke. Brain. 2015; 138(7): 1932–1948.
- Jian J, Konopka J, Liu C. Insights into the role of progranulin in immunity, infection, and inflammation. J Leukoc Biol. 2013; 93(2): 199–208.
- Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015; 36(7): 461–470.
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