Role of adiponectin in ovarian follicular development and ovarian reserve

Merhi,Zaher; Bazzi,Ali  A.; Bonney,Elizabeth  A.; Buyuk,Erkan

doi:10.3892/br.2019.1213

Role of adiponectin in ovarian follicular development and ovarian reserve

Authors:
- Zaher Merhi
- Ali A. Bazzi
- Elizabeth A. Bonney
- Erkan Buyuk
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Affiliations: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10463, USA, Department of Obstetrics and Gynecology, St. John Hospital and Medical Center, Detroit, MI 48236, USA, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT 05401, USA, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology and Women's Health, Montefiore's Institute for Reproductive Medicine and Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Published online on: May 17, 2019 https://doi.org/10.3892/br.2019.1213
Pages: 337-342

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Abstract

Adiponectin levels are associated with anti‑Müllerian hormone (AMH) and kisspeptin levels in non‑ovarian tissues. The objective of the present study was to investigate the association between adiponectin and the genes important for ovarian follicular development and ovarian reserve, specifically AMH and kisspeptin, and their corresponding receptors. In the first experiment, the mRNA levels of anti‑Müllerian hormone (amh) and its receptor (Amhr2), as well as those of kisspeptin (Kiss1) and its receptor (Kiss1r), were quantified by reverse transcription‑polymerase chain reaction analysis in the ovaries of two groups of mice [adiponectin‑knockout (KO) vs. control] that underwent oophorectomy. The second experiment measured follicular phase serum AMH and follicular fluid adiponectin levels in 25 women who underwent controlled ovarian hyperstimulation for in vitro fertilization. Compared with the control mice, adiponectin‑KO mice had 6.5 times lower Kiss1 mRNA levels (P=0.009) and a tendency for lower ovarian Kiss1r mRNA expression levels (P=0.06). However, adiponectin‑KO mice had significantly higher Amhr2 mRNA levels (P=0.01). In all women participants, there was a positive correlation between serum AMH and follicular fluid adiponectin concentrations (r=0.54, P=0.006). The findings of the present study indicate that adiponectin may play a role in ovarian physiology through its impact on genes crucial for ovarian follicular development and ovarian reserve, such as kisspeptin and AMH. Understanding the role of adiponectin in ovarian function may improve our knowledge of the pathophysiology underlying ovulatory dysfunction in obese women, who usually have low adiponectin levels, and overcome reproductive barriers.

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1	Hales CM, Carroll MD, Fryar CD and Ogden CL: Prevalence of obesity among adults and youth: United States, 2015-2016. NCHS Data Brief. 1–8. 2017.PubMed/NCBI
2	Wang YC, McPherson K, Marsh T, Gortmaker SL and Brown M: Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 378:815–825. 2011.PubMed/NCBI View Article : Google Scholar
3	Tzeng CR, Chang YC, Chang YC, Wang CW, Chen CH and Hsu MI: Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age. Fertil Steril. 101:1404–1410. 2014.PubMed/NCBI View Article : Google Scholar
4	Wei S, Schmidt MD, Dwyer T, Norman RJ and Venn AJ: Obesity and menstrual irregularity: Associations with SHBG, testosterone, and insulin. Obesity (Silver Spring). 17:1070–1076. 2009.PubMed/NCBI View Article : Google Scholar
5	Wise MR, Jordan V, Lagas A, Showell M, Wong N, Lensen S and Farquhar CM: Obesity and endometrial hyperplasia and cancer in premenopausal women: A systematic review. Am J Obstet Gynecol. 214(689): e1–-689.e17. 2016.PubMed/NCBI View Article : Google Scholar
6	Massetti GM, Dietz WH and Richardson LC: Excessive weight gain, obesity, and cancer: Opportunities for clinical intervention. JAMA. 318:1975–1976. 2017.PubMed/NCBI View Article : Google Scholar
7	Lee B and Shao J: Adiponectin and energy homeostasis. Rev Endocr Metab Disord. 15:149–156. 2014.PubMed/NCBI View Article : Google Scholar
8	Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, et al: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 257:79–83. 1999.PubMed/NCBI View Article : Google Scholar
9	Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, Ouchi N, Kihara S, Kawamoto T, Sumitsuji S, et al: Association of adiponectin mutation with type 2 diabetes: A candidate gene for the insulin resistance syndrome. Diabetes. 51:2325–2328. 2002.PubMed/NCBI View Article : Google Scholar
10	Ohashi K, Ouchi N, Kihara S, Funahashi T, Nakamura T, Sumitsuji S, Kawamoto T, Matsumoto S, Nagaretani H, Kumada M, et al: Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease. J Am Coll Cardiol. 43:1195–1200. 2004.PubMed/NCBI View Article : Google Scholar
11	Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K and Tobe K: Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 116:1784–1792. 2006.PubMed/NCBI View Article : Google Scholar
12	Nigro E, Scudiero O, Ludovica MM, Palmieri A, Mazzarella G, Costagliola C, Bianco A and Daniele A: New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int Article. 2014(658913)2014.PubMed/NCBI View Article : Google Scholar
13	Michalakis KG and Segars JF: The role of adiponectin in reproduction: From polycystic ovary syndrome to assisted reproduction. Fertil Steril. 94:1949–1957. 2010.PubMed/NCBI View Article : Google Scholar
14	Chabrolle C, Tosca L and Dupont J: Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction. 133:719–731. 2007.PubMed/NCBI View Article : Google Scholar
15	Ledoux S, Campos DB, Lopes FL, Dobias-Goff M, Palin MF and Murphy BD: Adiponectin induces periovulatory changes in ovarian follicular cells. Endocrinology. 147:5178–5186. 2006.PubMed/NCBI View Article : Google Scholar
16	Chabrolle C, Tosca L, Crochet S, Tesseraud S and Dupont J: Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in chicken ovary: Potential role in ovarian steroidogenesis. Domest Anim Endocrinol. 33:480–487. 2007.PubMed/NCBI View Article : Google Scholar
17	Cheng L, Shi H, Jin Y, Li X, Pan J, Lai Y, Lin Y, Jin Y, Roy G, Zhao A and Li F: Adiponectin deficiency leads to female subfertility and ovarian dysfunctions in mice. Endocrinology. 157:4875–4887. 2016.PubMed/NCBI View Article : Google Scholar
18	Liu YH, Tsai EM, Wu LC, Chen SY, Chang YH, Jong SB and Chan TF: Higher basal adiponectin levels are associated with better ovarian response to gonadotropin stimulation during in vitro fertilization. Gynecol Obstet Invest. 60:167–170. 2005.PubMed/NCBI View Article : Google Scholar
19	Richards JS, Liu Z, Kawai T, Tabata K, Watanabe H, Suresh D, Kuo FT, Pisarska MD and Shimada M: Adiponectin and its receptors modulate granulosa cell and cumulus cell functions, fertility, and early embryo development in the mouse and human. Fertil Steril. 98:471–479.e1. 2012.PubMed/NCBI View Article : Google Scholar
20	Chang HJ, Lee JH, Lee JR, Jee BC, Suh CS and Kim SH: Relationship between follicular fluid adipocytokines and the quality of the oocyte and corresponding embryo development from a single dominant follicle in in vitro fertilization/intracytoplasmic sperm injection cycles. Clin Exp Reprod Med. 41:21–28. 2014.PubMed/NCBI View Article : Google Scholar
21	Seifer DB and Maclaughlin DT: Mullerian Inhibiting Substance is an ovarian growth factor of emerging clinical significance. Fertil Steril. 88:539–546. 2007.PubMed/NCBI View Article : Google Scholar
22	van Rooij IA, Broekmans FJ, te Velde ER, Fauser BC, Bancsi LF, de Jong FH and Themmen AP: Serum anti-Müllerian hormone levels: A novel measure of ovarian reserve. Hum Reprod. 17:3065–3071. 2002.PubMed/NCBI View Article : Google Scholar
23	Freeman EW, Gracia CR, Sammel MD, Lin H, Lim LC and Strauss JF III: Association of anti-mullerian hormone levels with obesity in late reproductive-age women. Fertil Steril. 87:101–106. 2007.PubMed/NCBI View Article : Google Scholar
24	Buyuk E, Seifer DB, Illions E, Grazi RV and Lieman H: Elevated body mass index is associated with lower serum anti-mullerian hormone levels in infertile women with diminished ovarian reserve but not with normal ovarian reserve. Fertil Steril. 95:2364–2368. 2011.PubMed/NCBI View Article : Google Scholar
25	Wen JP, Liu C, Bi WK, Hu YT, Chen Q, Huang H, Liang JX, Li LT, Lin LX and Chen G: Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons. J Endocrinol. 214:177–189. 2012.PubMed/NCBI View Article : Google Scholar
26	Hameed S, Jayasena CN and Dhillo WS: Kisspeptin and fertility. J Endocrinol. 208:97–105. 2011.PubMed/NCBI View Article : Google Scholar
27	de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL and Milgrom E: Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. 100:10972–10976. 2003.PubMed/NCBI View Article : Google Scholar
28	Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, et al: The GPR54 gene as a regulator of puberty. N Engl J Med. 349:1614–1627. 2003.PubMed/NCBI View Article : Google Scholar
29	Terao Y, Kumano S, Takatsu Y, Hattori M, Nishimura A, Ohtaki T and Shintani Y: Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta. Biochim Biophys Acta. 1678:102–110. 2004.PubMed/NCBI View Article : Google Scholar
30	Kołodziejski PA, Pruszyńska-Oszmałek E, Korek E, Sassek M, Szczepankiewicz D, Kaczmarek P, Nogowski L, Maćkowiak P, Nowak KW, Krauss H and Strowski MZ: Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women. Physiol Res. 67:45–56. 2018.PubMed/NCBI View Article : Google Scholar
31	Merhi Z, Buyuk E, Berger DS, Zapantis A, Israel DD, Chua S Jr and Jindal S: Leptin suppresses anti-Mullerian hormone gene expression through the JAK2/STAT3 pathway in luteinized granulosa cells of women undergoing IVF. Hum Reprod. 28:1661–1669. 2013.PubMed/NCBI View Article : Google Scholar
32	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
33	Nelson SM, Stewart F, Fleming R and Freeman DJ: Longitudinal assessment of antimüllerian hormone during pregnancy-relationship with maternal adiposity, insulin, and adiponectin. Fertil Steril. 93:1356–1358. 2010.PubMed/NCBI View Article : Google Scholar
34	Park HT, Cho GJ, Ahn KH, Shin JH, Kim YT, Hur JY, Kim SH, Lee KW and Kim T: Association of insulin resistance with anti-Mullerian hormone levels in women without polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf). 72:26–31. 2010.PubMed/NCBI View Article : Google Scholar
35	Mahmoodzadeh Sagheb M, Azarpira N and Yaghobi R: The effect of leptin and adiponectin on KiSS-1 and KissR mRNA expression in rat islets of langerhans and CRI-D2 cell line. Int J Endocrinol Metab. 12(e15297)2014.PubMed/NCBI View Article : Google Scholar
36	Ahima RS and Lazar MA: Adipokines and the peripheral and neural control of energy balance. Mol Endocrinol. 22:1023–1031. 2008.PubMed/NCBI View Article : Google Scholar
37	Zhou Q, Chen H, Yang S, Li Y, Wang B, Chen Y and Wu X: High-fat diet decreases the expression of Kiss1 mRNA and kisspeptin in the ovary, and increases ovulatory dysfunction in postpubertal female rats. Reprod Biol Endocrinol. 12(127)2014.PubMed/NCBI View Article : Google Scholar
38	Latif R, Rafique N, Salem AM, AlSheikh MH and Chathoth S: Correlation between circulatory Kisspeptin and Adipokines in normal and over-weight Saudi females during menstrual cycle. Biol Rhythm Res. 49:169–174. 2018. View Article : Google Scholar
39	Merhi Z, Thornton K, Bonney E, Cipolla MJ, Charron MJ and Buyuk E: Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1. J Assist Reprod Genet. 33:535–543. 2016.PubMed/NCBI View Article : Google Scholar