Obesity and metabolic syndrome associated with systemic inflammation and the impact on the male reproductive system

Kristian Leisegang1, Ralf Henkel2,3, Ashok Agarwal3
1School of Natural Medicine, University of the Western Cape, Bellville, Cape Town, South Africa
2Department of Medical Biosciences, University of the Western Cape, Bellville, Cape Town, South Africa
3Department of Urology, American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, Ohio

Tóm tắt

Abstract

Obesity and metabolic syndrome (MetS) are global epidemics, driven by an obesogenic environment. This is mediated by complex underlying pathophysiology, in which chronic inflammation is an important aetiological and mechanistic phenomenon. A shift towards a subclinical TH1–lymphocyte mediated innate and chronic inflammatory response is well defined in obesity and MetS, demonstrated in multiple systems including visceral adiposity, brain (hypothalamus), muscles, vasculature, liver, pancreas, testes, epididymis, prostate and seminal fluid. Inflammatory cytokines disrupt the hypothalamic‐pituitary‐testes axis and steroidogenesis cascades (hypogonadotropic hypogonadism), spermatogenesis (poor semen parameters, including DNA fragmentation and detrimental epigenetic modification) and results in subclinical prostatitis and prostate hyperplasia. This review aims to highlight the role of chronic inflammation in obesity and MetS, cytokines in male reproductive physiology and pathophysiology, the impact on steroidogenesis and spermatogenesis, prostate pathology and erectile dysfunction. Currently, it is recommended that clinical assessment of male infertility and reproductive dysfunction in obese and MetS patients includes inflammation assessment (highly sensitive C‐reactive protein), and appropriate advice and therapeutic options are incorporated in the management options. However, the mechanisms and therapeutic options remain poorly understood and require significant interdisciplinary research to identify potential novel therapeutic strategies.

Từ khóa


Tài liệu tham khảo

10.1038/oby.2001.123

McPherson NO, 2015, Male obesity and subfertility, is it really about increased adiposity?, Asian J Androl, 17, 450, 10.4103/1008-682X.148076

10.2164/jandrol.107.003731

10.1161/CIRCULATIONAHA.109.192644

10.1155/2018/4274361

Castro AM, 2017, Low‐grade inflammation and its relation to obesity and chronic degenerative diseases, Rev Med Hosp Gen (Mex), 80, 101

10.1111/j.1524-6175.2006.04751.x

10.1111/j.1442-2042.2009.02280.x

10.1111/j.1743-6109.2009.01601.x

10.1038/pcan.2012.44

10.1111/bju.12728

10.4103/1008-682X.122341

10.5534/wjmh.180055

World Health Organisation, 2010, WHO Laboratory Manual for the Examination and Processing of Human Semen

10.1111/j.1365-2605.2005.00630.x

10.4111/icu.2017.58.6.385

10.1530/REP-07-0152

10.1111/j.1439-0272.2009.01002.x

10.1111/j.1439-0272.2010.01117.x

10.1016/j.aju.2017.11.008

10.1002/j.1939-4640.2004.tb02785.x

10.1111/j.1745-7262.2007.00238.x

10.1016/B978-0-12-812501-4.00013-4

10.1007/s10620-008-0585-3

10.1172/JCI57132

Pinte L, 2019, Non‐alcoholic fatty pancreas disease ‐ practices for clinicians, Rom J Intern Med

10.3748/wjg.v22.i34.7660

10.1093/humupd/dms050

10.5534/wjmh.180114

10.1016/j.fertnstert.2004.03.056

10.1093/humrep/dep075

10.1038/nrurol.2010.6

10.4161/spmg.21362

10.1016/j.fertnstert.2008.08.026

10.1093/humupd/dmp047

10.1093/humrep/det428

10.1186/1477-7827-12-34

10.1016/j.fertnstert.2010.11.044

10.3109/14647273.2015.1070438

Marchiani S, 2014, Metabolic syndrome‐associated sperm alterations in an experimental rabbit model: relation with metabolic profile, testis and epididymis gene expression and effect of tamoxifen treatment, Mol Cell Endocrinol, 401, 12, 10.1016/j.mce.2014.11.005

10.1530/REP-10-0472

10.1111/and.12060

10.1111/aji.12529

10.1100/2012/985201

10.1111/j.1365-2605.2010.01121.x

10.1111/j.2047-2927.2012.00031.x

10.1186/s12986-018-0274-y

10.1172/JCI200319451

10.1016/j.arcmed.2008.09.005

10.1016/j.mce.2009.08.018

10.1155/2010/289645

10.1016/j.amjcard.2010.02.017

10.1007/s00345-011-0726-8

10.1093/humupd/dmy009

Juge‐Aubry CE, 2005, Adipose tissue: a regulator of inflammation, J Clin Endocrinol Met, 19, 547

10.1038/nm.1964

10.1210/jc.2006-1055

10.1038/nature01137

10.1016/S0939-4753(04)80048-6

Camera A, 2008, Metabolic syndrome: from insulin resistance to adipose tissue dysfunction, Minerva Med, 99, 307

10.1038/sj.ijo.0802260

10.1210/en.2010-0336

10.1093/humrep/12.7.1476

10.1016/S0165-0378(01)00063-8

10.1016/j.fertnstert.2006.08.103

10.1093/humrep/dem281

10.1007/s00240-002-0269-y

10.1111/j.1600-0897.2009.00736.x

10.3389/fphys.2017.01117

10.1093/humupd/dmx033

10.1111/andr.12296

10.1159/000489918

10.1590/S1677-5538.IBJU.2014.0244

10.4103/aja.aja_67_18

Demirci T, 2019, The effect of chronic stress and obesity on sperm quality and testis histology in male rats; a morphometric and immunohistochemical study, Histol Histopathol, 34, 287

10.1080/15376516.2018.1543745

10.1007/s00345-003-0365-9

10.4161/spmg.1.2.16956

10.1016/S0165-0378(02)00060-8

10.1002/jemt.20704

Winter AG, 2014, Androgen defeciency and metabolic syndrome in men, Transl Androl Urol, 3, 50

10.1016/S0165-0378(02)00020-7

10.1016/j.mce.2003.11.022

10.1128/MCB.24.7.2593-2604.2004

10.1159/000366210

10.1046/j.1439-0272.2003.00572.x

10.1097/MOU.0b013e3283336f3f

10.1530/JOE-11-0289

10.1016/j.eururo.2011.11.013

Gorbachinsky I, 2010, Metabolic syndrome and urologic diseases, Rev Urol, 12, 157

10.1016/j.jsbmb.2012.02.007

10.1016/j.jri.2013.02.004

10.1016/S0090-4295(98)00390-2

10.1016/j.eururo.2013.02.038

10.1111/jcmm.13994

Morelli A, 2016, Hypogonadotropic hypogonadism and metabolic syndrome: insights from the high‐fat diet experimental rabbit animal model, Minerva Endocrinol, 41, 240

10.1371/journal.pone.0030571

10.1016/j.mce.2013.09.017

10.1172/JCI59660

Abdel‐Fadeil MR, 2019, Experimental obesity and diabetes reduce male fertility: potential involvement of hypothalamic Kiss‐1, pituitary nitric oxide, serum vaspin and visfatin, Pathophysiology, S0928‐4680(18)3

10.1111/j.1743-6109.2005.20103.x

Khalaf I, 2003, Efficacy and safety of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in Egypt and South Africa, Int J Impot Res, 15, 25

10.2164/jandrol.05136

Madersbacher S, 2004, Prevalence and risk factors for erectile dysfunction in 2869 men using a validated questionnaire, Eur Urol, 47, 80

10.1111/j.1743-6109.2010.01762.x

10.5534/wjmh.180026

10.1001/jama.294.23.2996

10.2174/1381612822666161019150241

10.1161/01.ATV.0000065195.22904.FA

10.1111/j.1743-6109.2011.02277.x

10.1111/j.1743-6109.2009.01624.x

10.4103/1008-682X.137687

10.1371/journal.pone.0103809

10.1016/j.chom.2017.10.005

10.1007/s11894-017-0600-y

10.1007/s13679-015-0152-0

10.1016/j.dsx.2016.01.024

10.1080/19490976.2017.1293224

10.3389/fmicb.2019.00234

10.1111/cen.12591

10.2174/1871530319666181130142642

10.1186/1742-4755-8-24

Jaffar M, 2016, Does weight loss improve fertility with respect to semen parameters? Results from a large cohort study, Int J Infertil Fetal Med, 7, 94

10.1093/nutrit/nuv059

10.1093/humupd/dmx006

Karayiannis D, 2016, Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility, Human Reprod, 32, 215

10.1017/S0007114518003240

10.1186/s12862-016-0768-z

10.1016/j.exger.2013.03.007

10.1126/science.273.5271.59

10.1007/s11357-013-9563-6

10.1177/1933719112440053

10.1016/j.rbmo.2011.10.014

10.1093/humrep/deh707

10.1093/humrep/deh569

10.2174/1871530315666150316124019

10.1371/journal.pone.0183506

10.1080/13813455.2018.1543329

10.1111/bph.12522

10.1530/REP-17-0390

10.1016/j.urology.2013.08.019

10.1080/09546630410017275

10.1124/jpet.301.2.418

10.1038/39335

10.1080/13813450802181047

10.1007/s10787-018-0508-7

10.1016/j.phrs.2017.01.032

10.1097/HJH.0000000000001086

10.1016/j.atherosclerosis.2017.01.009

10.1007/s12610-009-0030-2

10.1039/C8FO01259H

10.1016/j.etp.2015.01.001

10.1016/j.foodchem.2016.09.179