Adiponectin, the most abundant adipose-released cytokine, has an important role in metabolism, primarily through reducing insulin resistance. Reproductive functions are known to be influenced by energy balance and adiponectin may be involved in the underlying mechanisms connecting reproduction and metabolism. Interestingly, adiponectin has been shown to exert actions in the female reproductive system, including the hypothalamic–pituitary–ovarian axis and the endometrium. The peripheral effects of this adipocytokine are mediated mainly via 2 receptors, AdipoR1 and AdipoR2. The expression of these receptors has been reported in the brain, ovaries, endometrium, and the placenta. Thus, adiponectin may influence fertility and pregnancy. Furthermore, adiponectin concentrations and effects have been assessed in some pregnancy-associated disorders and gynecological conditions. The findings may lead to the use of adiponectin or its receptors as therapeutic targets in novel treatment strategies of these disorders.
MichalakisKGSegarsJH. The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction. Fertil Steril. 2010;94(6):1949–1957.
2.
BudakEFernández SánchezMBellverJCerveróASimónCPellicerA. Interactions of the hormones leptin, ghrelin, adiponectin, resistin and PYY3-36 with the reproductive system. Fertil Steril. 2006;85(6):1563–1581.
3.
KadowakiTYamauchiT. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26(3):439–451.
4.
BergAHCombsTPSchererPE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab. 2002;13(2):84–89.
5.
CombsTPBergAHRajalaMWSexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes. 2003;52(2):268–276.
6.
XuAChanKWHooRLTestosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem. 2005;280(18):18073–18080.
7.
AritaYKiharaSOuchiNParadoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79–83.
8.
HuELiangPSpiegelmanBM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996;271(18):10697–10703.
9.
YamauchiTKamonJWakiHThe fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941–946.
10.
QiYTakahashiNHilemanSMAdiponectin acts in the brain to decrease body weight. Nat Med. 2004;10(5):524–529.
11.
YamauchiTKamonJMinokoshiYAdiponectin stimulates glucose utilisation and fatty acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8(11):1288–1295.
12.
YamauchiTKamonJItoYCloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762–769.
HugCWangJAhmadNSBoganJSTsaoTS, Lodish HF. t-Cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci U S A. 2004;101(28):10308–10313.
15.
YamauchiTKadowakiT. Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes. 2008;32(suppl 7):13–18.
16.
JonesHJanssonTPowellTL. Full-length adiponectin attenuates insulin signaling and inhibits insulin-stimulated amino acid transport in human primary trophoblast cells. Diabetes. 2010;59(5):1161–1170.
17.
ThundyilJPavlovskiDSobeyCGArumugamTV. Adiponectin receptor signalling in the brain. Br J Pharmacol. 2012;165(2):313–327.
18.
WenJPLvWSYangJGlobular adiponectin inhibits GnRH secretion from GT1-7 hypothalamic GnRH neurons by induction of hyperpolarization of membrane potential. Biochem Biophys Res Commun. 2008;371(4):756–761.
19.
LuMTangQOlefskyJMMellonPLWebsterNJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LbetaT2 gonadotropes. Mol Endocrinol. 2008;22(3):760–771.
20.
PsilopanagiotiAPapadakiHKraniotiEFAlexandridesTKVarakisJN. Expression of adiponectin and adiponectin receptors in human pituitary gland and brain. Neuroendocrinology2009;89(1):38–47.
21.
PanWTuHKastinAJ. Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin. Peptides2006;27(4):911–916.
22.
SprangerJVermaSGohringIAdiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells. Diabetes2006;55(1):141–147.
23.
WakiHYamauchiTKamonJImpaired multimerization of human adiponectin mutans associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem. 2003;278(41):40352–40363.
24.
KusminskiCMMcTernanPGSchrawTAdiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum. Diabetologia. 2007;50(3):634–642.
25.
MaddineniSMetzgerSOconOHendricksG IIIRamachandranR. Adiponectin gene is expressed in multiple tissues in the chicken: food deprivation influences adiponectin messenger ribonucleic acid expression. Endocrinology. 2005;146(10):4250–4256.
26.
WenJLiuCEBiWAdiponectin inhibits KiSS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons. J Endocrinol. 2012;214:177–189.
27.
ChengXBWenJPYangJYangYNingGLiXY. GnRH secretion is inhibited by adiponectin through activation of AMP-activated protein kinase and extracellular signal-regulated kinase. Endocrine. 2011;39(1):6–12.
28.
HoydaTDFryMAhimaRSFergusonAV. Adiponectin selectively inhibits oxytocin neurons of the paraventricular nucleus of the hypothalamus. J Physiol. 2007;585(Pt 3):805–816.
29.
DupontJChabrolleCRaméCToscaLCoyral-CastelS. Role of the peroxisome proliferator-activated receptors, adenosine monophosphate-activated kinase, and adiponectin in the ovary. PPAR Res. 2008;2008:176275.
30.
MaillardVUzbekovaSGuignotFEffect of adiponectin on bovine granulosa cell steroidogenesis, oocyte maturation, and embryodevelopment. Reprod Biol Endocrinol. 2010;8:23.
31.
ChabrolleCToscaLCrochetSTesseraudSDupontJ. Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in chicken ovary: potential role in ovarian steroidogenesis. Domest Anim Endocrinol. 2007;33(4):480–487.
32.
ChabrolleCToscaLDupontJ. Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotropin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction. 2007;133(4):719–731.
33.
ChappazEAlbornozMSCamposDAdiponectin enhances in vitro development of swine embryos. Domest Anim Endocrinol. 2008;35(2):198–207.
34.
LagalyDVAadPYGrado-AhuirJAHulseyLBSpicerLJ. Role of adiponectin in regulating ovarian theca and granulose cell function. Mol Cell Endocrinol. 2008;284(1-2):38–45.
35.
GutmanGBarakVMaslovitzSAmitALessingJBGevaE. Recombinant luteinizing hormone induces increased production of ovarian follicular adiponectin in vivo: implications for enhanced insulin sensitivity. Fertil Steril. 2009;91(5):1837–1841.
36.
DafopoulosKSourlasDKallitsarisAPournarasSMessinisIE. Blood ghrelin, resistin, and adiponectin concentrations during the normal menstrual cycle. Fertil Steril. 2009;92(4):1389–1394.
37.
ChalvatzasNDafopoulosKKosmasGKallitsarisAPournarasSMessinisIE. Effect of ovarian hormones on serum adiponectin and resistin concentrations. Fertil Steril. 2009;91(4):1189–1194.
38.
TothMJCooperBCPratleyREMariAMatthewsDECassonPR. Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion. Am J Physiol Endocrinol Metab. 2008;294(6):E1035–1045.
39.
LiuYHTsaiEMChenYLSerum adiponectin levels increase after human chorionic gonadotropin treatment during in vitro fertilization. Gynecol Obstet Invest. 2006;62(2):61–65.
40.
BersingerNABirkhauserMHWunderDM. Adiponectin as a marker of success in inracytoplasmic sperm injection/embryo transfer cycles. Gynecol Endocrinol. 2006;22(9):479–483.
41.
LiuYHTsaiEMWuLCHigher basal adiponectin levels are associated with better ovarian response to gonadotropin stimulation during in vitro fertilization. Gynecol Obstet Invest. 2005;60(3):167–170.
42.
LordELedouxSMurphyBDBeaudryDPalinMF. Expression of adiponectins and its receptors in swine. J Anim Sci. 2005;83(3):565–578.
43.
TakemuraYOsugaYYamauchiTExpression of adiponectin receptors and its possible implication in the human endometrium. Endocrinology. 2006;147(7):3203–3210.
44.
Dos SantosESerazinVMorvanCAdiponectin and leptin systems in human endometrium during window of implantation. Fertil Steril. 2012;97(3):771–778.
45.
BenaitreauDDieudonnéMNDos SantosELeneveuMCde MazancourtPPecqueryR. Antiproliferative effects of adiponectin on human trophoblastic cell lines JEG-3 and BeWo. Biol Reprod. 2009;80(6):1107–1114.
46.
ChenJTanBKarterisESecretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia. 2006;49:1292–1302.
47.
CaminosJENogueirasRGallegoRExpression and regulation of adiponectin and receptor in human and rat placenta. J Clin Endocrinol Metab. 2005;90(7):4276–4286.
48.
PinarHBasuSHotmireKHigh molecular mass multimer complexes and vascular expression contribute to high adiponectin in the fetus. J Clin Endocrinol Metab. 2008;93(7):2885–2890.
49.
CorbettaSBulfamanteGCortelazziDAdiponectin expression in human fetal tissues during mid- and late gestation. J Clin Endocrinol Metab. 2005;90(4):2397–2402.
50.
McDonaldEAWolfeMW. Adiponectin attenuation of endocrine function within human term trophoblast cells. Endocrinology. 2009;150(9):4358–4365.
51.
TieWYuHChenJWangXChenWZhouR. Expressions of adiponectin receptors in placenta and their correlation with preeclampsia. Reprod Sci. 2009;16(7):676–684.
52.
Mazaki-ToviSKanetyHParienteCDetermining the source of fetal adiponectin. J Reprod Med. 2007;52(9):774–778.
53.
KadowakiKWaguriMNakanishiIAdiponectin concentration in umbilical cord serum is positively associated with the weight ratio of fetus to placenta. J Clin Endocrinol Metab. 2006;91(12):5090–5094.
54.
SivanEMazaki-ToviSParienteCAdiponectin in human cord blood: relation to fetal birth weight and gender. J Clin Endocrinol Metab. 2003;88(12):5656-5660.
55.
KotaniYYokotaIKitamuraSMatsudaJNaitoEKurodaY. Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight. Clin Endocrinol (Oxf). 2004;61(4):418–423.
56.
Mazaki-ToviSKanetyHParienteCHemiRSchiffESivanE. Cord blood adiponectin in large-for-gestational age newborns. Am J Obstet Gynecol. 2005;193(3 Pt 2):1238–1242.
57.
MantzorosCSRifas-ShimanSLWilliamsCJFargnoliJLKelesidisTGillmanMW. Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age: a prospective cohort study. Pediatrics. 2009;123(2):682–689.
58.
ChenLNyombaBLG. Glucose intolerance and resistin expression in rat offspring exposed to ethanol in utero: modulation by postnatal high fat diet. Endocrinology. 2003;144(2):500–508.
59.
ChenLZhangTNyombaBLG. Insulin resistance of gluconeogenic pathways in neonatal rats after prenatal ethanol exposure. Am J Physiol Regul Integr Comp Physiol. 2004;286(3):554–559.
60.
KalampokasEVrachnisNSamoliEAssociation of adiponectin and placental growth factor in amniotic fluid with second trimester fetal growth. In Vivo. 2012;26(2):327–333.
61.
HersougLGLinnebergA. The link between the epidemics of obesity and allergic diseases: does obesity induce decreased immune tolerance?Allergy. 2007;62(10):1205–1213.
62.
MantzorosCSPetridouEAlexeDMSerum adiponectin concentrations in relation to maternal and perinatal characteristics in newborns. Eur J Endocrinol. 2004;151(6):741–746.
63.
Mazaki-ToviSKanetyHParienteCMaternal serum adiponectin levels during human pregnancy. J Perinatol. 2007;27(2):77–81.
64.
CatalanoPMHoeghMMiniumJAdiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism. Diabetologia. 2006;49(7):1677–1685.
65.
López-BermejoAFernández-RealJMGarridoMaternal soluble tumour necrosis factor receptor type 2 (sTNFR2) and adiponectin are both related to blood pressure during gestation and infant's birthweight. Clin Endocrinol (Oxf). 2004;61(5):544–552.
66.
ChengMHWangPH. Placentation abnormalities in the pathophysiology of preeclampsia. Expert Rev Mol Diagn. 2009;9(1):37–49.
67.
JarvenpaaJVuoristoJTSantaniemiMAdiponectin induced placental cell apoptosis could be mediated via the AdipoR1-receptor in preeclampsia with IUGR. J Perinat Med. 2009;37(3):257–262.
68.
NandaSYuCKGiurcaneanuLAkolekarRNicolaidesKH. Maternal serum adiponectin at 11-13 weeks of gestation in preeclampsia. Fetal Diagn Ther. 2011;29(3):208–215.
69.
FasshauerMWaldeyerTSeegerJCirculating high-molecular-weight adiponectin is upregulated in preeclampsia and is related to insulin sensitivity and renal function. Eur J Endocrinol. 2008;158(2):197–201.
70.
D’AnnaRBavieraGCorradoFAdiponectin and insulin resistance in early - and late-onset pre-eclampsia. BJOG. 2006;113(11):1264–1269.
71.
SuwakiNMasuyamaHNakatsukasaHHypoadiponectinemia and circulating angiogenic factors in overweight patients complicated with pre-eclampsia. Am J Obstet Gynecol. 2006;195(6):1687–1692.
72.
Abd-AlaleemDIAttiaaKIKhalefaAAAhmadRA. Adiponectin levels in serum of women with preeclampsia. East Mediterr Health J. 2011;17(7):575–581.
73.
LiuYZhuLPanYSunLChenDLiX. Adiponectin levels in circulation and breast milk and mRNA expression in adipose tissue of preeclampsia women. Hypertens Pregnancy. 2012;31(1):40–49.
74.
OglandBRomundstadPRVefringHFormanMRNilsenSTVattenLJ. Preeclampsia and adiponectin in cord blood. Horm Res Paediatr. 2010;74(2):92–97.
75.
ValdésERLattesKAMuñozHSBarjaPYPapapietroKV. First-trimester adiponectin and subsequent development of preeclampsia or fetal growth restriction. Gynecol Obstet Invest. 2011;72(3):152–156.
76.
DalamagaMSrinivasSKElovitzMAChamberlandJMantzorosCS. Serum adiponectin and leptin in relation to risk for preeclampsia: results from a large case-control study. Metabolism. 2011;60(11):1539–1544.
77.
CombsTPBergAHObiciSSchererPERossettiL. Endogenous glucose production is inhbited by the adipose-derived protein Acrp 30. J Clin Invest. 2001;108(12):1875–1881.
78.
HaraKYamauchiTKadowakiT. Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans. Curr Diab Rep. 2005;5(2):136–140.
79.
BergAHCombsTPDuXBrownleeMSchererPE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 2001;7(8):947–953.
80.
LeeYHMagkosFMantzorosCSKangES. Effects of leptin and adiponectin on pancreatic β-cell function. Metabolism. 2011;60(12):1664–1672.
81.
Zavalza-GomezABAnaya-PradoRRincon-SanchesARMora-MartinezJM. Adipokines and insulin resistance during pregnancy. Diab Res Clin Pract. 2008;80(1):8–15.
82.
RamosMPCrespo-SolansMDdel CampoSCachoJHereraF. Fat accumulation in the rat during early pregnancy is modulated by enhanced insulin responsiveness. Am J Physiol Endocrinol Metab. 2003;285(2):E318–328.
83.
LeivaAPardoFRamírezMAFaríasMCasanelloPSobreviaL. Fetoplacental vascular endothelial dysfunction as an early phenomenon in the programming of human adult diseases in subjects born from gestational diabetes mellitus or obesity in pregnancy. Exp Diabetes Res. 2011;2011:349286.
84.
CatalanoPM. Increasing maternal obesity and weight gain during pregnancy: the obstetric problems of plentitude. Obstet Gyneocol. 2007;110(4):743–744.
85.
ThyfaultJPHedbergEMAnchanRMGestational diabetes is associated with depressed adiponectin levels. J Soc Gynecol Investig. 2005;12(1):41–45.
86.
VitoratosNDeliveliotouAVlachosNFMastorakosGPapadiasKBotsisD. Serum adiponectin during pregnancy and postpartum in women with gestational diabetes and normal controls. Gynecol Endocrinol. 2008;24(11):614–619.
87.
Gueuvoghlanian-SilvaBYTorloniMRMattarRProfile of inflammatory mediators in gestational diabetes mellitus: phenotype and genotype. Am J Reprod Immunol. 2012;67(3):241–250.
88.
BallesterosMSimónIVendrellJMaternal and cord blood adiponectin multimeric forms in gestational diabetes mellitus: a prospective analysis. Diabetes Care. 2011;34(11):2418–2423.
89.
KinalskiMTelejkoBKuźmickiMKretowskiAKinalskaI. Tumor necrosis factor alpha system and plasma adiponectin concentration in women with gestational diabetes. Horm Metab Res. 2005;37(7):450–454.
90.
StuebeAMMantzorosCKleinmanKGestational glucose tolerance and maternal metabolic profile at 3 years postpartum. Obstet Gynecol. 2011;118(5):1065–1073.
91.
VrachnisNBelitsosPSifakisSRole of adipokines and other inflammatory mediators in gestational diabetes mellitus and previous gestational diabetes mellitus. Int J Endocrinol. 2012;2012:549748.
92.
DunaifA. Insulin resistance and the polycystic ovary syndrome: mechanisms and implications for pathogenesis. Endocrine Reviews. 1997;18(6):774–800.
93.
CarminaE. Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines. Minerva Ginecol. 2004;56(1):1–6.
94.
ToscaLChabrolleCDupontJ. AMPK: a link between metabolism and reproduction?Med Sci (Paris). 2008;24(3):297–300.
95.
van HoutenELKramerPMcLuskeyAKarelsBThemmenAPVisserJA. Reproductive and metabolic phenotype of a mouse model of PCOS. Endocrinology. 2012;153(6):2861–2869.
96.
ArodaVCiaraldiTPChangSADahanMHChangRJHenryRR. Circulating and cellular adiponectin in polycystic ovary syndrome: relationship to glucose tolerance and insulin action. Fertil Steril. 2008;89(5):1200–1208.
97.
YilmazMBukanNDemirciHSerum resistin and adiponectin levels in women with polycystic ovary syndrome. Gynecol Endocrinol. 2009;25(4):246–252.
98.
ToulisKAGoulisDGFarmakiotisDGeorgopoulosNAKatsikisITarlatzisBC. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update. 2009;15(3):297–307.
99.
MazloomiSSharifiFHajihosseiniRKalantariSMazloomzadehS. Association between hypoadiponectinemia and low serum concentrations of calcium and vitamin D in women with polycystic ovary syndrome. ISRN Endocrinol. 2012;2012:949427.
100.
BikWBaranowska-BikAWolinska-WitortEChmielowskaMMartynskaLBaranowskaB. The relationship between metabolic status and levels of adiponectin and ghrelin in lean women with polycystic ovary syndrome. Gynecol Endocrinol. 2007;23(6):325–331.
DucluzeauPHCousinPMalvoisinEGlucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(8):3626–3631.
103.
AydogduAUckayaGTasciIThe relationship of epicardial adipose tissue thickness to clinical and biochemical features in women with polycystic ovary syndrome. Endocr J. 2012;59(6):509–516.
104.
TakemuraYOsugaYHaradaMSerum adiponectin concentrations are decreased in women with endometriosis. Hum Reprod. 2005;20(12):3510–3513.
105.
YiKWShinJHParkHTKimTKimSHHurJY. Resistin concentration is increased in the peritoneal fluid of women with endometriosis. Am J Reprod Immunol. 2010;64(5):318–323.
106.
PandeyNKriplaniAYadavRKLyngdohBTMahapatraSC. Peritoneal fluid leptin levels are increased but adiponectin levels are not changed in infertile patients with pelvic endometriosis. Gynecol Endocrinol. 2010;26(11):843–849.
107.
TakemuraYOsugaYHaradaMConcentration of adiponectin in peritoneal fluid is decreased in women with endometriosis. Am J Reprod Immunol. 2005;54(4):217–221.
108.
WakabayashiATakedaTTsuijiKAntiproliferative effect of adiponectin on rat uterine leiomyoma ELT-3 cells. Gynecol Endocrinol. 2011;27(1):33–38.
109.
ChenHSChanTFChungYFSuJHYuanSS. Aberrant serum adiponectin levels in women with uterine leiomyomas. Gynecol Obstet Invest. 2004;58(3):160–163.
110.
WuXYanQZhangZDuGWanX. Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells. Oncol Rep. 2012;27(5):1488–1496.
111.
MoonHSChamberlandJPAronisKTseleni-BalafoutaSMantzorosCS. Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans. Mol Cancer Ther. 2011;10(12):2234–2243.
112.
BarbDWilliamsCJNeuwirthAKMantzorosCS. Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr. 2007;86(3):858–866.
113.
MuNZhuYWangYZhangHXueF. Insulin resistance: a significant risk factor of endometrial cancer. Gynecol Oncol. 2012;125(3):751–757.
114.
ChenXXiangYBLongJRGenetic polymorphisms in obesity-related genes and endometrial cancer risk. Cancer. 2012;118(13):3356–3364.
115.
SolimanPTCuiXZhangQHankinsonSELuKH.Circulating adiponectin levels and risk of endometrial cancer: the prospective Nurses' Health Study. Am J Obstet Gynecol. 2011;204(2):167.e1–5.
116.
AshizawaNYahataTQuanJAdachiSYoshiharaKTanakaK. Serum leptin-adiponectin ratio and endometrial cancer risk in postmenopausal female subjects. Gynecol Oncol. 2010;119(1):65–69.
