• Users Online: 284
  • Print this page
  • Email this page

 
Table of Contents
REVIEW ARTICLE
Year : 2019  |  Volume : 8  |  Issue : 5  |  Page : 244-250

Adiponectin in male reproduction and infertility


1 Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Malaysia
2 Department of Physiology, Faculty of Medicine and Biomedical Sciences, MAHSA University, Malaysia

Date of Submission25-May-2019
Date of Decision28-Jun-2019
Date of Acceptance25-Jul-2019
Date of Web Publication07-Oct-2019

Correspondence Address:
Sulagna Dutta
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University
Malaysia
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2305-0500.268153

Rights and Permissions
  Abstract 


Adiponectin is an adipokine that has the highest plasma concentration among all other adipokines. It is a white adipose tissue secretion essential for the regulation of energy metabolism owing to its antiatherogenic insulin-resistance, and anti-inflammatory properties. Studies have put forth that adiponectin is a potent endocrine regulator with mechanisms relating energy balance with reproductive function in different species, including humans. The two adiponectin receptors, AdipoR1 and AdipoR2 have been found to be expressed in the prime regulatory axis of reproduction, the hypothalamic-pituitary-gonadal axis. The activation of adiponectin receptors has been shown to regulate the secretion and gene expressions of kisspeptin, gonadotropin-releasing hormone and gonadotropins. Adiponectin finds relevance in the regulations of most of the vital testicular functions, such as steroidogenesis, germ cell proliferation and their coordinated apoptosis, as well as in modulation of testicular redox status and oxidative stress. Since metabolic syndrome and their associations with male infertility have been gaining immense research interest, adiponectin seems to be one of the important mediators of metabolic syndrome-induced male reproductive dysfunctions. This article aims to review the patterns of adiponectin expression in the male reproductive tissues and the mechanism by which adiponectin modulates male reproductive functions.

Keywords: Adiponectin, Male fertility, Semen quality


How to cite this article:
Dutta S, Sengupta P, Biswas A. Adiponectin in male reproduction and infertility. Asian Pac J Reprod 2019;8:244-50

How to cite this URL:
Dutta S, Sengupta P, Biswas A. Adiponectin in male reproduction and infertility. Asian Pac J Reprod [serial online] 2019 [cited 2021 Sep 29];8:244-50. Available from: http://www.apjr.net/text.asp?2019/8/5/244/268153




  1. Introduction Top


The white adipose tissue, besides a toxic depot of triglycerides, is considered as a vital endocrine organ releasing an array of hormones or adipokines, whose mechanism of actions has still not been completely explained[1]. The main purpose of these adipokines is the maintenance of energy homeostasis, while their crosstalks with other endocrine axes as well as their direct impact upon other organs are surfacing with the advent of research in these realms[2]. The adipose tissue hormonal milieu is jeopardized in case of metabolic syndrome such as obesity[3], whose prevalence is accelerating at alarming rate all over the world. The concurrent global decline in male fertility[4],[5],[6],[7],[8], has led to a substantial number of researches directed to unveil the exact association between metabolic disorders like in case of obesity and male reproductive dysfunctions[9],[10].

Adiponectin is found to the most abundant adipokine in the serum, and its role in the maintenance of insulin sensitivity and in the pathogenesis of the metabolic syndrome is well known. The expressions of adiponectin and its receptors in the organs concerned with reproductive functions have attracted research interests to find its participation in modulating reproductive functions. The role of adiponectin in influencing the secretion and release of the hormones of the prime reproductive regulatory axis, the hypothalamic-pituitary-gonadal (HPG) axis, has been evidenced through several studies. Their expressions and functions in testicular cells have also been documented. Therefore, its high time to explore the role and mechanism of action by which adiponectin may influence male fertility, which may in part explain the association of metabolic balance with male reproductive functions. This article aims to review the expressions and properties of adiponectin and its receptors, its role in regulating the HPG axis and in influencing the key testicular functions.


  2. Structural characteristics of adiponectin Top


2.1. Adiponectin gene

Adiponectin, produced by the white adipose tissues, is a proteinaceous hormone with four synonyms. It may be refered to asadipocyte complement-related protein with a molecular weight of 30 kDa, gelatin binding protein with molecular weight of 28 kDa, adipose most abundant gene transcript 1 (apM1) and adiponectin, C1q and collagen domain-containing. In the year 1999, the name adiponectin was coined first time during the configuration of the above mentioned four nucleotide sequences[11]. Human apM1 16kb gene consists of 3 exons and 2 introns, which shows 3 homologous genes encoded with collagen VIII, X and C1q complements[12]. Various controlling segments of apM1 gene expression have been recognized in the vicinity of the exon 1 gene. With the contrast of other genes, apM1 do not possess TATA sequences except numerous transcriptional parameters[13]. Hence, the protein synthesis activity of adiponectin can be controlled by several pathways.

2.2. Adiponectin protein

Human adiponectin contains 244 amino acids, and has the molecular weight of 30 kDa with four different domains: a carboxy-terminal globular chain of 137- amino acids, an amino-terminal with 18 amino acids, a very species hypervariable chain with 23 amino acids and an acid collagen domain with 66 amino acids where 22 are repeat motif variables[14]. This type of adiponectin generally looks with an extended appearance. Though it contains a smaller version also, that is a fragmented product of elastase enzyme which is produced by the leukocytes such as neutrophils and monocytes. From the collagen domain, numerous proteolytic sites have been identified with different locations. The smaller form of adiponectin conserves its bulbous sphere veracity and forwards its effects with bonding receptors[15]. As compared to human, rat adiponectin contains 247-amino acid sequences[16]. It is produced from the adipose tissues to the main circulation with 3 protein complexes. These are trimer with molecular weight of 67 kDa, two trimers of 130 kDa, known as hexamer and a larger molecular weight protein with 300 kDa[17]. Under inhabitant circumstances, adiponectin remains imperceptible as a monomer. Hence, it is an indispensable situation for adiponectin to undergo polymerization to maintain its natural action as a protein[18]. Therefore, it forms as lesser molecular weight trimers which in turn ascertain the hydrophobic bonds between spherical and collagen domains with distinct noncovalent α-helices connections[19]. The shorter adiponectin cannot polymerize any more. On the other hand, the longer adiponectin trimers can polymerize repeatedly to form medium and high molecular weight hexamers, which can rise up to 18 or more monomers. After translational alterations is essential for these adiponectin polymerizations[18]. Undeniably, hexamers are the product of disulphide bonds between two successive cysteines, and are present at the different part of the adiponectin. Studies revealed that various forms of adiponectin fractions display diverse natural actions. For instance, low molecular weight adiponectin exhibits more potent anti-inflammatory measures in contrast with high molecular weight adiponectin, which are almost 70% of the total adiponectin circulating in a normal human blood may responsible for the insulin sensitivity[15],[20].

Adipokine moves in the circulation with high levels (3 to 30 μg/mL), and hence it constitutes up to 0.01% of the total plasma proteins in various species, such as rats, pigs, chicken, turkeys, cows, and humans [21],[22],[23],[24]. Human blood carries only 10% of low molecular weight proteins as compared to medium and high molecular weight proteins, which together constitutes 90% of the total proteins circulated in the blood[25]. The negligible amount of spherical protein is present in the blood circulation. In the cow’s blood, prior to calving, plasma adiponectin level becomes least and at the beginning of the lactation it reaches the highest level. In contrast with humans and rats, cow’s blood contains high molecular weight proteins in a larger quantity, whereas trimeric and spherical adiponectin remains undetected[26],[27]. In several other species, plasma adiponectin level holds positive correlations with a wide range of reproductive dysfunctions, such as gestational diabetes, preeclampsia, polycystic ovarian syndrome, ovarian cancer, etc[28]. Several pathophysiological parameters are closely related to adiponectin expression in human. Its concentrations in plasma are directly signified with the levels of adiposity and they are controled by the dietary conditions also. Studies on rats and sheep revealed that adiponectin’s level has been raised during the fasting period and reversed back after meal[29],[30]. It has been documented that adiponectin can be found in higher quantity in female rats and humans. However, under few definite circumstances it can be low also. Findings of Cnop et al revealed that prior to the menopause, adiponectin concentration was low as compared to the post-menopausal women[31], though there are no confirmatory findings yet regarding this. Researches on mice show that adiponectin level in plasma was four times more in the adult females than the younger ones. Because of the low availability of adiponectin in the obese person as compared to the control, it confirms that there is a direct correlation between obesity and adiponectin concentration in the adipose tissues which may be responsible for the several metabolic disorders[25],[32].


  3. Adiponectin receptors Top


Adiponectin is primarily active through AdipoR1 and AdipoR2 seven transmembrane receptors, which differ from the other G protein receptors. During intracellular signal transduction, these receptors are extremely indispensable to have a zinc-binding motif[33]. AdipoR1 and AdipoR2 preserved 67% amino acid sequences structurally[33],[34]. AdipoR1 has more affinity towards spherical adiponectin and less affinity towards long-chain adiponectin of skeletal muscles, whereas, AdipoR2 has a medium affinity for both spherical and long-chain adiponectin of the hepatocytes[35]. Many similar types of AdipoR receptors may be present but have not been confirmed yet. In hypothalamic cells, adiponectin contains independent AdipoR receptors. In the same way tissue macrophages also contains AdipoR receptors and T-cadherin and adiponectin still have its effect on the interfering RNA biologically[34].

Many cell signaling pathways can be activated by the adiponectin receptors, though they cannot be able to show any effect on kinase or phosphorylation. Tyrosine residues couldn’t interrupt the targeted mutagenesis of these receptors in adiponectin signaling[36]. Hence, the participation of the intermediate molecules during the commencement of transduction pathways after bonding with adiponectin receptors made the structural conformation. AdipoR1 and R2 receptors are capable of binding with adaptor protein phosphotyrosine (APPL1), which can interact with pleckstrin homology and leucine zipper1 protein. Another different protein, called APPL2 can control the binding of APPL1 protein with adiponectin[36]. When adiponectin signal is unavailable, APPL2 can link with N-terminal part of the adiponectin receptors; similarly, it can form an APPL1/APPL2 dimer, which can stop this bonding with adiponectin. In contrast, this binding helps to separate adiponectin from similar dimer. Thus, APPL proteins can control adiponectin signaling[34].


  4. Adiponectin mediated signaling pathways Top


After linking with its receptors, adiponectin initiates several signaling pathways in different cells, such as mitogen-activated protein kinase and extracellular signal-regulated kinases 1/2, serine/threonine-protein kinase and adenosine monophosphate-activated protein kinase (AMPK). Adiponectin can phosphorylate the transcript factor and peroxisome proliferator-activated receptor-alpha. Hence, adiponectin can be able to control these signaling pathways in a variety of functions in the body[34],[35].


  5. Effect of adiponectin in HPG axis Top


The HPG axis is considered the prime regulatory endocrine axis in monitoring the functions of the male reproductive system. It is conventionally known that the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus triggers the release of gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. These gonadotropins act on their receptors on testicular cells, Leydig cells and Sertoli cells to coordinate the processes of steroidogenesis and spermatogenesis. This regulatory axis receives negative or positive feedback from the testicular and other hormones and factors as per the requirement for physiological homeostasis. Expression of adiponectin and both of its receptors, AdipoR1 and AdipoR2 have been evidenced in the human hypothalamus and pituitary suggesting its importance in the regulatory mechanism of HPG axis[37],[38]. Moreover, its deficiency has been suggested to have inhibitory effects over FSH and LH secretion thereby jeopardizing reproductive functions[39]. The influence of adiponectin over the hypothalamic GnRH secretions can be predicted through the study that observed mutation in adiponectin gene significantly reduced the number of GnRH immunoreactive neurons[39].


  6. Adiponectin and hypothalamus Top


Expression of adiponectin receptors in the hypothalamus is evident in different species as well as in humans[40],[41]. Its predominance in the cerebrospinal fluid may indicate its autocrine or paracrine actions over the hypothalamic-pituitary axes[37],[42]. It has been shown that in murine models, peripheral intravenous adiponectin administration results in a concurrent increase in adiponectin levels in the cerebrospinal fluid which is suggestive of its ability to cross the blood-brain barrier[42],[43]. Adiponectin concentrations also have been reported to elevate during fasting and get reduced after refeeding[29].

As discussed earlier, hypothalamic GnRH neurons are the main regulatory components of the reproductive axis, which controls the secretion and release of pituitary gonadotropins. In vitro studies have demonstrated that adiponectin inhibits hypothalamic GnRH secretions through activation ofAMPK[44]. Experiments in a matured immortalized murine hypothalamic GnRH neuronal cell line (GT1-7 cells) showed that adiponectin inhibited the GnRH secretion along with suppressing the expressions of KISS1 mRNA[45],[46]. Kisspeptins, hypothalamic neuropeptides, which by binding to their receptors (KISS1-R) are reported to mediate the mechanism of triggering the physiological onset of puberty by induction of hypothalamic GnRH. Thus, it may be suggested that adiponectin may reduce GnRH secretion by influencing the kisspeptins mediated GnRH inducing signal. A hypothesis of adiponectin actions upon the GnRH neuron suggests that murine GnRH neurons highly express the adiponectin receptor, and AdipoR2 acting through which adiponectin perhaps activate the protein kinase Cζ/liver kinase B1/AMPK signaling pathway to rapidly decrease GnRH neuronal activity[47].


  7. Adiponectin and pituitary Top


Alike in the hypothalamic neurons, the adiponectin and its receptors have been found in the pituitary of different species, including human[38],[48]. In human, adiponectin has been found in all the pituitary cells responsible for the production of hormones of reproductive importance, such as LH, FSH, thyroid-stimulating hormone, growth hormone[38]. The adiponectin receptors have also been found to be expressed in these pituitary cells, such as in the gonadotrophs, thyrotrophin, somatotrophs but not were found in the lactotrophs or corticotrophs[38]. Adiponectin has been shown to inhibit the basal and GnRH mediated LH secretion in rat and mouse pituitary cells in vitro[49]. Moreover, adiponectin has been reported to downregulate the gene expressions for GnRH receptor[50]. The effects of adiponectin upon FSH release from porcine primary pituitary cells have been shown to be stimulatory[48]. Adiponectin also reportedly could modulate both GnRH and insulin-mediated secretions of LH and FSH. There are observations from two normal nonhuman-primate species, suggesting that adiponectin has no influence upon the LH and FSH release by primary pituitary cell cultures[51]. However, from the above discussions, it is clear that majority of the studies have unveiled the expressions and actions of adiponectin and its receptors in the hypothalamus and pituitary modulating the secretion and release of key reproductive hormones, GnRH, LH, and FSH. Thus, adiponectin plays important roles in influencing the hypothalamic-pituitary axis in the control of reproductive functions. It has been explained that FSH helps in initiation of spermatogenesis by acting on its receptors on the testicular Sertoli cells, and in combination with high intratesticular testosterone, it plays role in the sustenance of spermatogenesis. It is well known that LH regulates androgen synthesis or steroidogenesis by acting upon its receptors on the testicular Leydig cells.


  8. Adiponectin on testicular functions Top


8.1. Adiponectin in seminal fluid

Semen or seminal fluid is the male body fluid containing spermatozoa and have been reported to contain adiponectin at concentrations of about 66- and 180-folds less that is serum concentrations in men and bulls, respectively[28],[52]. Moreover, it has been stipulated that adiponectin concentrations in seminal fluid are positively correlated with that in blood plasma, suggesting it is transferred from the blood to testicular cells traversing the blood- testis barrier.

8.2. Adiponectin expression in testicular cells

Expression of adiponectin and its receptors are immensely reported in human testicular cells, especially in the Leydig cells, while the spermatozoa also have been shown to express its receptors[53]. AdipoR2 gene knockout murine model demonstrated aspermia atrophy in their seminiferous tubules and enlarged brains, while the testosterone levels remained unchanged[54]. It has also been demonstrated that in the murine model, with the advancement of age, there is a reduction in the testicular expressions of adiponectin and its receptors[55]. It may be inferred that an adequate adiponectin concentration and expressions of its receptors may be essential for normal testicular functions. Adiponectin therapy may possess potent antiaging characters and may ameliorate and promote normal testicular activities in old aged men.


  9. Regulation of reproductive functions in different reproductive ages Top


Adiponectin receptor mRNA expressions in chicken displayed modifications during the puberty. Their expressions were found to be increased in adulthood as compared to the levels of expression in the prepubertal phases[56]. In Leydig cells in rodents, the expressions of AdipoR2 protein as well the adiponectin serum concentrations, also showed an increase during puberty[57],[58]. These observations may indicate that either physiological changes through the puberty have led to upregulation in expressions of testicular adiponectin and its receptors, or adiponectin may have an essential role in initiating the physiological changes during puberty.


  10. Adiponectin and gonadal steroid hormones Top


There are surfacing evidences that are establishing close associations between adipose tissue-derived hormones, factors and other metabolic hormones with male reproductive functions[59],[60],[61],[62]. Studies also have put forth a link between adiponectin and steroid hormones, such as gonadal ablation in adult male mice showed an elevation in the levels of serum adiponectin[58],[63], while the levels were restored following testosterone administration[63]. In human, it has been shown that hypogonadism led an increase in serum adiponectin concentrations which got normalized by androgen supplementation[64]. A study in the rat has shown a relationship between testosterone and adiponectin. The study has conveyed that exposure to isoflavones during developmental period has elevated the adiponectin levels in serum while reduced the serum testosterone levels[57]. Porcine testicular extract demonstrated increase induction of adipose tissue to secrete adiponectin via the peroxisome proliferator-activated receptor signaling pathway[65]. These observations may indicate that adiponectin is one of the adipose tissue-derived hormones that actively participate in explaining the mechanism of association between metabolic balance with reproductive functions.


  11. Adiponectin as anti-inflammatory mediator in testis Top


Adiponectin has been claimed to have regulatory actions over both spermatogenesis and steroidogenesis via its receptors, AdipoR1 and AdipoR2[45],[66]. In vitro experiments demonstrated direct actions of adiponectin on Leydig cells to downregulate androgen secretions, via inhibiting the steroidogenic acute regulatory protein in Leydig cells[57].

Adiponectin, on binding to its receptors, may trigger the intracellular signaling cascades involving the proteins such as AMPK, peroxisome proliferator-activated receptor-alpha and mitogen-activated protein kinase[35]. This signaling pathway finds relevance in the regulation of testicular functions, essentially steroidogenesis[67]. The adiponectin induction of the testicular signaling pathway relevant for steroidogenesis suggests the role of adiponectin in regulating the process of testosterone production.

Another essential aspect of adiponectin action is its capability to sustain insulin sensitivity via induction of testicular glucose uptake[66]. It is well known that intratesticular glucose level is one of the major regulators of vital testicular functions such as steroidogenesis[68]. Exogenous administration of adiponectin in aged mice has shown to ameliorate testicular mass and functions via elevated expressions of the insulin receptor, inducing the activities of antioxidative enzymes, testosterone biosynthesis along with testicular glucose and lactate uptake by an increased tumor of glucose and lactate transporter proteins[55].

Adiponectin also displays some anti-inflammatory properties that render protection to the Leydig cells from inflammatory cytokines and chemokines-mediated cytotoxicity. Thus, adiponectin acts as a testicular defense mechanism to combat the impacts of pro- inflammatory mediators on steroidogenesis, such as those of the macrophage-derived tumor necrosis factor-α, interleukin 1, and interferon-γ[69].

The adiponectin signaling in male gonadal tissue seems to be essential for various testicular functions, but further clarifications are required to establish the exact level of contribution of the adiponectin mediated pathways on male reproduction.


  12. Adiponectin on sperm functaions Top


Kawwass et al had reported that spermatozoa also express adiponectin receptors[70]. Its receptor, AdipoR1 had been shown to be expressed mainly by the sperm equatorial and acrosome regions, while the AdipoR2 expressions were mostly on the equatorial line and in the sperm head region[71].

Studies in bulls have shown that adiponectin concentrations in plasma and abundance of its receptor mRNA expressions in spermatozoa positively correlated with the conception rates in the female counterparts[71]. Seminal adiponectin concentration along with the presence of its receptors in ram sperm was also found to associate with the sperm motility parameters[72]. In human, seminal adiponectin concentrations positively correlate with semen quality in terms of sperm count, sperm concentration, and sperm morphology[52]. The adiponectin and its receptors reportedly decrease followed by capacitation, which may suggest a direct role of adiponectin in the regulation of sperm motility[52].


  13. Conclusions Top


This review article has presented a concise updated concept on expressions and functions of adiponectin and its receptors in the male reproductive system. Through this review, it is clearly discussed that adiponectin and its receptors are profuse in the central and peripheral reproductive tissues, and thereby it may be speculated that they are essential for the testicular functions as well as in regulating the HPG axis which is the prime endocrine axis for reproduction. Studies in human and various other animal models have demonstrated that adiponectin has regulatory actions on spermatogenesis, steroidogenesis, sperm motility and even has anti- inflammatory properties to protect testicular cells form inflammatory mediators. Further research is required to unveil the extent to which adiponectin system mediates male reproductive functions and whether it can be targeted for therapeutic interventions in male infertility or subfertility.

Conflict of interest statement

The authors declare that there is no conflict of interest.



 
  References Top

1.
Trayhurn P, Beattie JH. Physiological role of adipose tissue: White adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 2001; 60(3): 329-339.  Back to cited text no. 1
    
2.
Sengupta P, Dutta S, Tusimin M, Karkada IR. Orexins and male reproduction. Asian Pac JReprod 2019; 8(5): 233-238.  Back to cited text no. 2
    
3.
Darbandi M, Darbandi S, Agarwal A, Sengupta P, Durairajanayagam D, Henkel R, et al. Reactive oxygen species and male reproductive hormones. Reprod Biol Endocrinol 2018; 16(1): 87.  Back to cited text no. 3
    
4.
Sengupta P, Dutta S, Krajewska-Kulak E. The disappearing sperms: Analysis of reports published between 1980 and 2015. Am J Men’s Health 2017; 11(4): 1279-1304.  Back to cited text no. 4
    
5.
Sengupta P, Borges Jr E, Dutta S, Krajewska-Kulak E. Decline in sperm count in European men during the past 50 years. Hum Exp Toxicol 2018; 37(3): 247-255.  Back to cited text no. 5
    
6.
Sengupta P, Nwagha U, Dutta S, Krajewska-Kulak E, Izuka E. Evidence for decreasing sperm count in African population from 1965 to 2015. Afr Health Sci 2017; 17(2): 418-427.  Back to cited text no. 6
    
7.
Sengupta P, Dutta S, Tusimin MB, Irez T, Krajewska-Kulak E. Sperm counts in Asian men: Reviewing the trend of past 50 years. Asian Pac J Reprod 2018; 7(2): 87-92.  Back to cited text no. 7
    
8.
Sengupta P. Reviewing reports of semen volume and male aging of last 33 years: From 1980 through 2013. Asian Pac J Reprod 2015; 4(3): 242-246.  Back to cited text no. 8
    
9.
[9} Sengupta P. Current trends of male reproductive health disorders and the changing semen quality. Int J Prev Med 2014; 5(1): 1.  Back to cited text no. 9
    
10.
[10]Sengupta P. Recent trends in male reproductive health problems. Asian J Pharm Clin Res 2014; 7(2): 1-5.  Back to cited text no. 10
    
11.
Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Comm 1999; 257(1): 79-83.  Back to cited text no. 11
    
12.
Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Ini J Obesity 2000; 24(7): 861.  Back to cited text no. 12
    
13.
Liu M, Liu F. Transcriptional and post-translational regulation of adiponectin. Biochem J 2010; 425(1): 41-52.  Back to cited text no. 13
    
14.
Nishida M, Funahashi T, Shimomura I. Pathophysiological significance of adiponectin. Med Mol Morphol 2007; 40(2): 55-67.  Back to cited text no. 14
    
15.
Waki H, Yamauchi T, Kamon J, Kita S, Ito Y, Hada Y, et al. Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology 2005; 146(2): 790-796.  Back to cited text no. 15
    
16.
Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270(45): 26746-26749.  Back to cited text no. 16
    
17.
Hada Y, Yamauchi T, Waki H, Tsuchida A, Hara K, Yago H, et al. Selective purification and characterization of adiponectin multimer species from human plasma. Biochem Biophys Res Comm 2007; 356(2): 487-493.  Back to cited text no. 17
    
18.
Wang Y, Lam KS, Yau M-h, Xu A. Post-translational modifications of adiponectin: Mechanisms and functional implications. Biochem J 2008; 409(3): 623-633.  Back to cited text no. 18
    
19.
Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 1998; 8(6): 335-340.  Back to cited text no. 19
    
20.
Wedellova Z, Kovacova Z, Tencerova M, Vedral T, Rossmeislova L, Siklova-Vitkova M, et al. The impact of full-length, trimeric and globular adiponectin on lipolysis in subcutaneous and visceral adipocytes of obese and non-obese women. PLoS One 2013; 8(6): e66783.  Back to cited text no. 20
    
21.
Swarbrick MM, Havel PJ. Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. Metab Syndr Related Dis 2008; 6(2): 87-102.  Back to cited text no. 21
    
22.
Chabrolle C, Tosca L, 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 2007; 133(4): 719-731.  Back to cited text no. 22
    
23.
Diot M, Reverchon M, Rame C, Froment P, Brillard JP, Brière S, et al. Expression of adiponectin, chemerin and visfatin in plasma and different tissues during a laying season in turkeys. Reprod Biol Endocrinol 2015; 13(1): 81.  Back to cited text no. 23
    
24.
Maleszka A, Smolinska N, Nitkiewicz A, Kiezun M, Chojnowska K, Dobrzyn K, et al. Adiponectin expression in the porcine ovary during the oestrous cycle and its effect on ovarian steroidogenesis. Int J Endocrinol 2014; 2014: 1-9  Back to cited text no. 24
    
25.
Combs TP, Marliss EB. Adiponectin signaling in the liver. Rev Endocr Metab Dis 2014; 15(2): 137-147.  Back to cited text no. 25
    
26.
Singh S, Häussler S, Gross JJ, Schwarz F, Bruckmaier R, Sauerwein H. Circulating and milk adiponectin change differently during energy deficiency at different stages of lactation in dairy cows. J Dairy Sci 2014; 97(3): 1535-1542.  Back to cited text no. 26
    
27.
Mellouk N, Rame C, Touzé JL, Briant E, Ma L, Guillaume D, et al. Involvement of plasma adipokines in metabolic and reproductive parameters in Holstein dairy cows fed with diets with differing energy levels. J Dairy Sci 2017; 100(10): 8518-8533.  Back to cited text no. 27
    
28.
Heinz JF, Singh SP, Janowitz U, Hoelker M, Tesfaye D, Schellander K, et al. Characterization of adiponectin concentrations and molecular weight forms in serum, seminal plasma, and ovarian follicular fluid from cattle. Theriogenology 2015; 83(3): 326-333.  Back to cited text no. 28
    
29.
Kubota N, Yano W, Kubota T, Yamauchi T, Itoh S, Kumagai H, et al. Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab 2007; 6(1): 55-68.  Back to cited text no. 29
    
30.
Wang R, Kuang M, Nie H, Bai W, Sun L, Wang F, et al. Impact of Food Restriction on the expression of the adiponectin system and genes in the hypothalamic-pituitary-ovarian axis of pre-pubertal ewes. Reprod Domest Anim 2016; 51(5): 657-664.  Back to cited text no. 30
    
31.
Cnop M, Havel P, Utzschneider K, Carr D, Sinha M, Boyko E, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: Evidence for independent roles of age and sex. Diabetologia 2003; 46(4): 459-469.  Back to cited text no. 31
    
32.
Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez- Chillaron JC, et al. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 2003; 52(2): 268-276.  Back to cited text no. 32
    
33.
Tanabe H, Fujii Y, Okada-Iwabu M, Iwabu M, Nakamura Y, Hosaka T, et al. Crystal structures of the human adiponectin receptors. Nature 2015; 520(7547): 312.  Back to cited text no. 33
    
34.
Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T. Adiponectin receptors: A review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab 2014; 28(1): 15-23.  Back to cited text no. 34
    
35.
Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005; 26(3): 439-451.  Back to cited text no. 35
    
36.
Mao X, Kikani CK, Riojas RA, Langlais P, Wang L, Ramos FJ, et al. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nature Cell Biol 2006; 8(5): 516.  Back to cited text no. 36
    
37.
Kos K, Harte AL, Da Silva NF, Tonchev A, Chaldakov G, James S, et al. Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus. J Clin Endocrinol Metab 2007; 92(3): 1129-1136.  Back to cited text no. 37
    
38.
Psilopanagioti A, Papadaki H, Kranioti EF, Alexandrides TK, Varakis JN. Expression of adiponectin and adiponectin receptors in human pituitary gland and brain. Neuroendocrinology 2009; 89(1): 38-47.  Back to cited text no. 38
    
39.
Cheng L, Shi H, Jin Y, Li X, Pan J, Lai Y, et al. Adiponectin deficiency leads to female subfertility and ovarian dysfunctions in mice. Endocrinology 2016; 157(12): 4875-4887.  Back to cited text no. 39
    
40.
Guillod-Maximin E, Roy A, Vacher C, Aubourg A, Bailleux V, Lorsignol A, et al. Adiponectin receptors are expressed in hypothalamus and colocalized with proopiomelanocortin and neuropeptide Y in rodent arcuate neurons. J Endocrinol 2009; 200(1): 93.  Back to cited text no. 40
    
41.
Kaminski T, Smolinska N, Maleszka A, Kiezun M, Dobrzyn K, Czerwinska J, et al. Expression of adiponectin and its receptors in the porcine hypothalamus during the oestrous cycle. Reprod Domest Anim 2014; 49(3): 378-386.  Back to cited text no. 41
    
42.
Kusminski C, McTernan P, Schraw T, Kos K, O’hare J, Ahima R, et al. Adiponectin complexes in human cerebrospinal fluid: Distinct complex distribution from serum. Diabetologia 2007; 50(3): 634-642.  Back to cited text no. 42
    
43.
Qi Y, Takahashi N, Hileman SM, Patel HR, Berg AH, Pajvani UB, et al. Adiponectin acts in the brain to decrease body weight. Nat Med 2004; 10(5): 524.  Back to cited text no. 43
    
44.
Cheng XB, Wen JP, Yang J, Yang Y, Ning G, Li XY. GnRH secretion is inhibited by adiponectin through activation of AMP-activated protein kinase and extracellular signal-regulated kinase. Endocrine 2011; 39(1): 6-12.  Back to cited text no. 44
    
45.
Wen JP, Liu C, Bi WK, Hu YT, Chen Q, Huang H, et al. Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons. J Endocrinol 2012; 214(2): 177.  Back to cited text no. 45
    
46.
Wen JP, Lv WS, Yang J, Nie AF, Cheng XB, Yang Y, et al. Globular adiponectin inhibits GnRH secretion from GT1-7 hypothalamic GnRH neurons by induction of hyperpolarization of membrane potential. Biochem Biophys Res Comm 2008; 371(4): 756-761.  Back to cited text no. 46
    
47.
Klenke U, Taylor-Burds C, Wray S. Metabolic influences on reproduction: Adiponectin attenuates GnRH neuronal activity in female mice. Endocrinology 2014; 155(5): 1851-1863.  Back to cited text no. 47
    
48.
Kiezun M, Smolinska N, Maleszka A, Dobrzyn K, Szeszko K, Kaminski T. Adiponectin expression in the porcine pituitary during the estrous cycle and its effect on LH and FSH secretion. Am J Physiol Endocrinol Metab 2014; 307(11): E1038-E1046.  Back to cited text no. 48
    
49.
Lu M, Tang Q, Olefsky JM, Mellon PL, Webster NJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LpT2 gonadotropes. Mol Endocrinol 2008; 22(3): 760-771.  Back to cited text no. 49
    
50.
Rodriguez-Pacheco F, Martinez-Fuentes AJ, Tovar S, Pinilla L, Tena- Sempere M, Dieguez C, et al. Regulation of pituitary cell function by adiponectin. Endocrinology 2007; 148(1): 401-410.  Back to cited text no. 50
    
51.
Sarmento-Cabral A, Peinado JR, Halliday LC, Malagon MM, Castaño JP, Kineman RD, et al. Adipokines (leptin, adiponectin, resistin) differentially regulate all hormonal cell types in primary anterior pituitary cell cultures from two primate species. Sci Rep 2017; 7: 43537.  Back to cited text no. 51
    
52.
Thomas S, Kratzsch D, Schaab M, Scholz M, Grunewald S, Thiery J, et al. Seminal plasma adipokine levels are correlated with functional characteristics of spermatozoa. Fertil Steril 2013; 99(5): 1256-1263. e3.  Back to cited text no. 52
    
53.
Martin LJ. Implications of adiponectin in linking metabolism to testicular function. Endocrine 2014; 46(1): 16-28.  Back to cited text no. 53
    
54.
Bjursell M, Ahnmark A, Bohlooly YM, William-Olsson L, Rhedin M, Peng XR, et al. Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes 2007; 56(3): 583-593.  Back to cited text no. 54
    
55.
Choubey M, Ranjan A, Bora PS, Baltazar F, Martin LJ, Krishna A. Role of adiponectin as a modulator of testicular function during aging in mice. Biochim Biophys Acta 2019; 1865(2): 413-427.  Back to cited text no. 55
    
56.
Ocon-Grove OM, Krzysik-Walker SM, Maddineni SR, Hendricks GL, Ramachandran R. Adiponectin and its receptors are expressed in the chicken testis: influence of sexual maturation on testicular ADIPOR1 and ADIPOR2 mRNA abundance. Reproduction 2008; 136(5): 627-638.  Back to cited text no. 56
    
57.
Pfaehler A, Nanjappa MK, Coleman ES, Mansour M, Wanders D, Plaisance EP, et al. Regulation of adiponectin secretion by soy isoflavones has implication for endocrine function of the testis. Toxicol Lett 2012; 209(1): 78-85.  Back to cited text no. 57
    
58.
Gui Y, Silha JV, Murphy LJ. Sexual dimorphism and regulation of resistin, adiponectin, and leptin expression in the mouse. Obes Res 2004; 12(9): 1481-1491.  Back to cited text no. 58
    
59.
Krajewska-Kulak E, Sengupta P. Thyroid function in male infertility. Front Endocrinol 2013; 4: 174.  Back to cited text no. 59
    
60.
Sengupta P, Dutta S. Thyroid disorders and semen quality. Biomed Pharmacol J 2018; 11(1): 01-10.  Back to cited text no. 60
    
61.
Irez T, Karkada IR, Dutta S, Sengupta P. Obestatin in male reproduction and infertility. Asian Pac J Reprod 2019; 8(5): 239-243.  Back to cited text no. 61
    
62.
Dutta S, Biswas A, Sengupta P, Nwagha U. Ghrelin and male reproduction. Asian Pac J Reprod 2019; 8(5): 227-232.  Back to cited text no. 62
    
63.
Yarrow JF, Beggs LA, Conover CF, McCoy SC, Beck DT, Borst SE. Influence of androgens on circulating adiponectin in male and female rodents. PLoS One 2012; 7(10): e47315.  Back to cited text no. 63
    
64.
Lanfranco F, Zitzmann M, Simoni M, Nieschlag E. Serum adiponectin levels in hypogonadal males: Influence of testosterone replacement therapy. Clin Endocrinol 2004; 60(4): 500-507.  Back to cited text no. 64
    
65.
Kadooka K, Sato M, Matsumoto T, Kuhara S, Katakura Y, Fujimura T. Pig testis extract augments adiponectin expression and secretion through the peroxisome proliferator-activated receptor signaling pathway in 3T3- L1 adipocytes. Cytotechnology 2018; 70(3): 983-992.  Back to cited text no. 65
    
66.
Choubey M, Ranjan A, Bora PS, Baltazar F, Krishna A. Direct actions of adiponectin on changes in reproductive, metabolic, and anti-oxidative enzymes status in the testis of adult mice. Gen Comp Endocrinol 2019; 279: 1-11.  Back to cited text no. 66
    
67.
Ahn SW, Gang GT, Tadi S, Nedumaran B, Kim YD, Park JH, et al. Phosphoenolpyruvate carboxykinase and glucose-6-phosphatase are required for steroidogenesis in testicular Leydig cells. J Biol Chem 2012; 287(50): 41875-41887.  Back to cited text no. 67
    
68.
Banerjee D, Mazumder S, Bhattacharya S, Sinha A. The sex specific effects of extraneous testosterone on ADP induced platelet aggregation in platelet-rich plasma from male and female subjects. Int J Lab Hematol 2014; 36(5): e74-e77.  Back to cited text no. 68
    
69.
Wu L, Xu B, Fan W, Zhu X, Wang G, Zhang A. Adiponectin protects Leydig cells against proinflammatory cytokines by suppressing the nuclear factor -κB signaling pathway. FEBS J 2013; 280(16): 3920-3927.  Back to cited text no. 69
    
70.
Kawwass JF, Summer R, Kallen CB. Direct effects of leptin and adiponectin on peripheral reproductive tissues: A critical review. Mol Hum Reprod 2015; 21(8): 617-632.  Back to cited text no. 70
    
71.
Kasimanickam VR, Kasimanickam RK, Kastelic JP, Stevenson JS. Associations of adiponectin and fertility estimates in Holstein bulls. Theriogenology 2013; 79(5): 766-777.  Back to cited text no. 71
    
72.
Kadivar A, Khoei HH, Hassanpour H, Golestanfar A, Ghanaei H. Correlation of adiponectin mRNA abundance and its receptors with quantitative parameters of sperm motility in rams. Int J Fertil Steril 2016; 10(1): 127.  Back to cited text no. 72
    



This article has been cited by
1 Irisin, Energy Homeostasis and Male Reproduction
Pallav Sengupta,Sulagna Dutta,Ivan Rolland Karkada,Roland Eghoghosoa Akhigbe,Suresh V. Chinni
Frontiers in Physiology. 2021; 12
[Pubmed] | [DOI]
2 Obesity and male infertility: Mechanisms and management
Kristian Leisegang,Pallav Sengupta,Ashok Agarwal,Ralf Henkel
Andrologia. 2020;
[Pubmed] | [DOI]
3 Interstitial Leydig Cell Tumorigenesis—Leptin and Adiponectin Signaling in Relation to Aromatase Expression in the Human Testis
Michal Duliban,Ewelina Gorowska-Wojtowicz,Waclaw Tworzydlo,Agnieszka Rak,Malgorzata Brzoskwinia,Izabella Krakowska,Jan K. Wolski,Malgorzata Kotula-Balak,Bartosz J. Plachno,Barbara Bilinska
International Journal of Molecular Sciences. 2020; 21(10): 3649
[Pubmed] | [DOI]
4 Hormones in male reproduction and fertility
Pallav Sengupta,Sulagna Dutta
Asian Pacific Journal of Reproduction. 2019; 8(5): 187
[Pubmed] | [DOI]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  2. Structural ch...3. Adiponectin r...4. Adiponectin m...5. Effect of adi...6. Adiponectin a...7. Adiponectin a...8. Adiponectin o...9. Regulation of...10. Adiponectin ...11. Adiponectin ...12. Adiponectin ...
  In this article
Abstract
1. Introduction
13. Conclusions
References

 Article Access Statistics
    Viewed1981    
    Printed138    
    Emailed0    
    PDF Downloaded237    
    Comments [Add]    
    Cited by others 4    

Recommend this journal