In our study the expression levels of

In our study, the expression levels of adiponectin and its receptors in the uteri, conceptuses, and throphoblasts were determined by the stage of early pregnancy. Therefore, it could be hypothesized that the adiponectin system is regulated by the local hormonal milieu. Hormonal regulation in the uterus and conceptuses during the peri-implantation period of porcine pregnancy has been studied extensively. The corpora lutea are essential for maintaining and establishing pregnancy, and they produce progesterone that stimulates secretory activity of the endometrium [37]. Estrogen (mainly estradiol), which is produced by conceptuses on Days 10 to 13 of gestation, is one of the signals for maternal recognition of pregnancy [38]. It has been suggested that estradiol increases PGE2 synthesis and the PGE2/PGF2α ratio [39]. The second estradiol peak occurs between Days 15 and 25 to 30 of gestation [40]. Various growth factors and cytokines are active in the uterine environment during the peri-implantation period, including FGF7, TGFβ, interleukin-1β, TNFα, IFND, and IFNG. Their expression is regulated by pregnancy hormones, and they modulate the expression of other genes in the uterus [41]. The changes in adiponectin system expression observed in our study during pregnancy are somewhat correlated with the described changes in the local hormonal milieu. The adiponectin system in the porcine uterus, placenta, and conceptuses could be regulated by some of the discussed steroids, prostaglandins, growth factors, cytokines, and many others factors. This statement could be supported by the studies of Kedenko et al. [42], in which they demonstrated that the adiponectin gene promoter region contains Batimastat for various types of nuclear receptors (PPARG2, LRH, and RXR), transcription factors (CEBPA, SREBP1c, TFAP2B, FOXO1, and SP1), and at least 3 coregulators of transcription factors (SIRT1, NCOR1, and NCOR2). However, further work is needed to confirm this hypothesis.
Acknowledgment This research was supported by National Science Centre, grant no: 2011/03/B/NZ9/04187.
Introduction As a major endocrine organ, adipose tissue secretes a number of biologically active adipokines such as adiponectin, leptin, TNFα, resistin and adipsin (Kadowaki and Yamauchi, 2005). Adiponectin was first identified from 3T3-L1 adipocytes in 1995 by Scherer et al. (Scherer et al., 1995). Adiponectin is composed of four distinct domains, including a signal peptide sequence at the N-terminus, a non-conserved variable region, a collagen-like domain, and a globular domain at the C-terminus (Scherer et al., 1995). Functional analysis shows that adiponectin plays an important role in multiple biological processes in humans (Shehzad et al., 2012). For example, adiponectin plays an important role in the regulation of fatty acid and glucose metabolism in skeletal, cardiac muscle and liver to maintain energy homeostasis. And adiponectin could promotes endothelial progenitor cell number and function (Karbowska and Kochan, 2006, Shibata et al., 2008). Adiponectin also has insulin-sensitizing, anti-diabetic, anti-atherogenic and anti-inflammatory properties (Kadowaki and Yamauchi, 2005, Tsubakio-Yamamoto et al., 2008). In addition, adiponectin has been shown to be involved in the regulation of reproduction and gonadotropic hormone synthesis/release in rat pituitaries (Rodriguez-Pacheco et al., 2007). In GT1-7 (subset strains of GT1 cell lines) cells, adiponectin inhibits GNRH secretion and suppresses Kiss1 mRNA transcription (Wen et al., 2012, Wen et al., 2008). Moreover, adiponectin decreases insulin-induced androstenedione and progesterone production (Kawwass et al., 2015, Lagaly et al., 2008). Adiponectin exerts its biological functions through three receptors: AdipoR1, AdipoR2 and T-cadherin (Kadowaki and Yamauchi, 2005). T-cadherin is a glycosylphosphatidylinositol-anchored extracellular protein (Hug et al., 2004). T-cadherin is mainly expressed in the heart and vasculature (Denzel et al., 2010), and acts as a co-receptor to facilitate adiponectin signaling by binding with HMW (High Molecular Weight) adiponectin (Hug et al., 2004). AdipoR1 and AdipoR2 are 7-transmembrane receptors, belonging to the PAQR (Progestin AdipoQ Receptor) protein family (Tang et al., 2005). The structure of AdipoR1 and AdipoR2, characteristic of N-terminus in internal and C-terminus in external, is opposite to the topology of GPCR (G protein-coupled receptors) (Yamauchi et al., 2003). The amino acid sequences of AdipoR1 and AdipoR2 show sequence homology of 67% (Yamauchi et al., 2003), and the physiological functions were divergent. AdipoR1 has a higher affinity to the globular adiponectin. And AdipoR2 shows an equal affinity to both full-length and globular adiponectin (Yamauchi et al., 2003). AdipoR1 is mainly expressed in skeletal muscle and liver and regulates glucose and lipid metabolism through AMPK (AMP-activated kinase) pathways (Kadowaki and Yamauchi, 2005, Yamauchi and Kadowaki, 2013). AdipoR2 is most abundantly expressed in white adipose tissue and liver, and involved in activation of PPARα (peroxisome proliferator-activated receptor alpha) pathways that regulate fatty-acid metabolism and inflammatory reaction (Kadowaki and Yamauchi, 2005).