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Adipokines play crucial roles in both reproductive and energy metabolic processes. This study aimed to compare the hormonal plasma profile of adiponectin, apelin, vaspin, chemerin, resistin, visfatin, and adipolin, and the expression of their receptors in the anterior pituitary (AP) between normal-weight Large White (LW) and fat Meishan (MS) pigs during different phases of the estrous cycle. We measured adipokine levels in the plasma and assessed their gene expression in the AP. We used Pearson's correlation analysis to examine potential links between adipokines levels, their receptors, and metabolic parameters (body weight; backfat thickness) and reproductive parameters (pituitary weight; age at puberty; levels of gonadotropins, steroid hormones; and gene expression of gonadotropin-releasing hormone receptor and gonadotropins in AP). The plasma levels of the evaluated adipokines fluctuated with phase and breed, except for visfatin and adipolin. Moreover, adipokine expression in AP varied significantly between breeds and estrous cycle phases, except for resistin receptor CAP1. Notably, we observed a positive correlation between plasma levels of adiponectin and its transcript in the AP only in MS pigs. Apelin gene expression correlated negatively with its receptor in MS, while we observed a breed-dependent correlation between chemerin gene expression and its receptor CMKLR1. We identified significant positive or negative correlations between adipokines or their receptor levels in plasma and AP as well as metabolic or reproductive parameters, depending on the breed. In conclusion, we have demonstrated breed-specific and estrous cycle-dependent regulation of adipokines in AP, underscoring their potential impact on metabolic and reproductive processes in swine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Reproductive success consists of a sequential events chronology, starting with the ovum fertilization, implantation of the embryo, placentation, and cellular processes like proliferation, apoptosis, angiogenesis, endocrinology, or metabolic changes, which taken together finally conduct the birth of healthy offspring. Currently, many factors are known that affect the regulation and proper maintenance of pregnancy in humans, domestic animals, or rodents. Among the determinants of reproductive success should be distinguished: the maternal microenvironment, genes, and proteins as well as numerous pregnancy hormones that regulate the most important processes and ensure organism homeostasis. It is well known that white adipose tissue, as the largest endocrine gland in our body, participates in the synthesis and secretion of numerous hormones belonging to the adipokine family, which also may regulate the course of pregnancy. Unfortunately, overweight and obesity lead to the expansion of adipose tissue in the body, and its excess in both women and animals contributes to changes in the synthesis and release of adipokines, which in turn translates into dramatic changes during pregnancy, including those taking place in the organ that is crucial for the proper progress of pregnancy, i.e. the placenta. In this chapter, we are summarizing the current knowledge about levels of adipokines and their role in the placenta, taking into account the physiological and pathological conditions of pregnancy, e.g. gestational diabetes mellitus, preeclampsia, or intrauterine growth restriction in humans, domestic animals, and rodents., (Copyright © 2024. Published by Elsevier Inc.)

In Brief: Adipolin (C1QTNF12) has been described as a regulator of metabolism and is linked with the pathophysiology of PCOS. In this study, for the first time, we show the expression of C1QTNF12 in granulosa cells and its positive effect on porcine granulosa cell proliferation and steroid synthesis., Abstract: Adipolin (C1QTNF12) is a recently discovered adipokine that plays an important role in glucose and insulin level regulation. Previous studies showed its reduced level in serum of women suffering from polycystic ovarian syndrome; however, whether C1QTNF12 regulates ovary function is still unknown. The aim of the study was first to determine the level of C1QTNF12 in the porcine ovarian follicles granulosa cells (Gc) and then its in vitro effect on proliferation and steroidogenesis as well as phosphorylation of several signalling pathways. Our results showed that the expression of C1QTNF12 was dependent on follicle size and was higher at the mRNA and protein level in Gc of small than large follicles from both prepubertal and mature animals. Similar pattern was observed for C1QTNF12 concentration in porcine follicular fluid. Additionally, we observed immunolocalisation of C1QTNF12 in Gc, theca cells and oocytes. We found that C1QTNF12 stimulated porcine Gc proliferation via the activation of protein kinase B (AKT). Moreover, C1QTNF12 enhanced progesterone, testosterone and oestradiol secretion by elevating STAR, CYP11A1, HSD3B and CYP19A1 mRNA expression and by activation of MAP3/1 pathway. Additionally, C1QTNF12 increased pMAP3/1-to-MAP3/1 protein expression ratio and enhanced IGF1-induced pTyr-IGF1Rβ-to-IGFR1β and pMAP3/1-to-MAP3/1 protein ratios. Taken together, C1QTNF12 could act directly on proliferation and steroid synthesis and serve as an important factor in in vivo ovarian follicle function, possibly regulating the course of folliculogenesis.

The prevalence of adult obesity has risen markedly in recent decades. The endocrine system precisely regulates energy balance, fat abundance and fat deposition. Interestingly, white adipose tissue is an endocrine gland producing adipokines, which regulate whole-body physiology, including energy balance and reproduction. Endocrine disruptor chemicals (EDCs) include natural substances or chemicals that affect the endocrine system by multiple mechanisms and increase the risk of adverse health outcomes. Numerous studies have associated exposure to EDCs with obesity, classifying them as obesogens by their ability to activate different mechanisms, including the differentiation of adipocytes, increasing the storage of triglycerides, or elevating the number of adipocytes. Moreover, in recent years, not only industrial deception and obesity have intensified but also the problem of human infertility. Reproductive functions depend on hormone interactions, the balance of which may be disrupted by various EDCs or obesity. This review gives a brief summary of common EDCs linked with obesity, the mechanisms of their action, and the effect on adipokine levels, reproduction and connected disorders, such as polycystic ovarian syndrome, decrease in sperm motility, preeclampsia, intrauterine growth restriction in females and decrease of sperm motility in males., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adipose tissue secretes multiple hormones termed adipokines, which are important regulators of many processes. There are four types of evidence supporting an association between adipokines and female fertility which are effects that occur: centrally at the pituitary; peripherally and locally at the ovary and reproductive tract; directly on the oocyte/embryo and during pregnancy. In this review, there was a focus on the description of adipokines (leptin, apelin, resistin, chemerin, adiponectin, vaspin and visfatin) on ovarian cell proliferation, cell cycle progression and apoptosis in comparison to effects on human and domestic animal ovaries including pigs, cattle and chickens. Knowledge about molecules which regulate the balance between proliferation and apoptosis so that these processes are optimal for ovarian function is essential for understanding the physiology and reducing the incidence of infertility. Furthermore, oogenesis, folliculogenesis, oocyte loss/selection and atresia are important processes for optimal ovarian physiological functions. There, however, is ovulation from only a few follicles, while the majority undergo atresia that is induced by apoptosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In pig, backfat deposition is strongly related to the growth and reproductive performance. However, the molecular regulatory mechanisms of adipose tissue are not clearly understood. Adipose tissue is now recognized as an important endocrine organ that secretes a variety of factors including adipokines. However, the regulation of expression pattern of these adipokines in both plasma and visceral white adipose tissue (WAT) in lean and fat pig is unclear. In the present study, we used two representative porcine breeds (Large White, LW; Meishan, MS) with contrasting backfat thickness and sexual maturity age. Using specific ELISA assays, we determined the plasma profile of eight adipokines, leptin, adiponectin, visfatin, apelin, chemerin, resistin, omentin and vaspin in LW and MS sows. By RT-qPCR and western-blot we also investigated the mRNA and protein levels of these adipokines and their cognate receptors (LEPR, ADIPOR1, ADIPOR2, CMKLR1, CCRL2, GPR1, APLNR, TLR4, ROR1, CAP1 and HSPA5) in the peri renal WAT, respectively. At both plasma and peri renal WAT level, we found that the amounts of leptin, chemerin, resistin and vaspin were higher whereas those of adiponectin and omentin were lower in MS than LW sows. Plasma and adipose tissue visfatin and apelin levels were not different between the two breeds. Moreover, we noted that the variations of peri renal WAT adipokines observed between MS and LW were similar at the protein and mRNA level except for chemerin and apelin suggesting post-transcriptional modifications for these two adipokines. Finally, among the eight adipokines studied, we showed that only the plasma concentrations of leptin and chemerin were positively and those of adiponectin, negatively associated with the thickness of fat and opposite correlation was found for the onset of puberty in both LW and MS animals. Taken together, these results support a potential involvement of adipokines in WAT regulation and its link with the onset of the puberty in sows., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the impact of the source of mesenchymal stem cells (MSCs) and their adipogenic derivatives on the relative abundances (RAs) noticed for mRNA transcripts of the selected adipokines (adiponectin and leptin) and their receptors. MSCs were isolated from bone marrow (BM) and subcutaneous adipose tissue (AT) samples collected post mortem from a total of four gilts (each at the age of 6 months). The stemness of the MSCs was proven via recognizing their abilities to differentiate into adipocytes, osteoblasts, and chondrocytes. By using real-time PCR (RT -qPCR), the quantitative levels of transcriptional activity pinpointed for the adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOR1), adiponectin receptor 2 (ADIPOR2), leptin (LEP), and leptin receptor (LEPR) genes were comparatively analyzed between non-differentiated AT -MSCs and BM-MSCs and their cell counterparts undergoing differentiation into adipocytes. A significantly higher RA for ADIPOR1 transcripts was identified in the AT-MSCs compared to the BM-MSCs and their adipogenic derivatives (P≤0.05). Moreover, the quantitative levels of LEPR transcripts were shown to increase significantly among adipocytes originating from differentiated BM-MSCs compared to undifferentiated BM-MSCs, AT -MSCs, and AT -MSC-derived adipocytes (P≤0.05). Nonetheless, there was no significant inter-group variability in the RAs of the ADIPOQ, ADIPOR2, or LEP mRNA transcripts (P>0.05). Cumulatively, the in vitro models focused on the identification and detailed exploration of transcriptomic signatures of undifferentiated pig BM- and AT -MSCs, and the molecular mechanisms underlying the adipogenic differentiation pathways of the above-indicated two distinct sources of stem cells were developed and optimized in the current investigation for the very first time. These ex vivo porcine models might confirm the expedited functional mobilization of ex situ-protected MSCs and their enhanced capacity to be transcriptionally reprogrammed into adipocytes due to physiopathological alterations in the expression profiles of adipokines and their receptors, which are prompted and progressed in obese and superobese women patients at the peri-pubertal period of ontogenesis. Finally, the models providing comprehensive molecular insights into ex situ-protected porcine BM- and AT -derived MSCs and their differentiated derivatives can be largely suitable for the biotechnologically assisted rescue and restitution of endangered representatives of rare native breeds of domestic pig. [ABSTRACT FROM AUTHOR]

In brief: Adipolin (C1QTNF12) has been described as a regulator of metabolism and is linked with the pathophysiology of PCOS. In this study, for the first time, we show the expression of C1QTNF12 in granulosa cells and its positive effect on porcine granulosa cell proliferation and steroid synthesis. Adipolin (C1QTNF12) is a recently discovered adipokine that plays an important role in glucose and insulin level regulation. Previous studies showed its reduced level in serum of women suffering from polycystic ovarian syndrome; however, whether C1QTNF12 regulates ovary function is still unknown. The aim of the study was first to determine the level of C1QTNF12 in the porcine ovarian follicles granulosa cells (Gc) and then its in vitro effect on proliferation and steroidogenesis as well as phosphorylation of several signalling pathways. Our results showed that the expression of C1QTNF12 was dependent on follicle size and was higher at the mRNA and protein level in Gc of small than large follicles from both prepubertal and mature animals. Similar pattern was observed for C1QTNF12 concentration in porcine follicular fluid. Additionally, we observed immunolocalisation of C1QTNF12 in Gc, theca cells and oocytes. We found that C1QTNF12 stimulated porcine Gc proliferation via the activation of protein kinase B (AKT). Moreover, C1QTNF12 enhanced progesterone, testosterone and oestradiol secretion by elevating STAR, CYP11A1, HSD3B and CYP19A1 mRNA expression and by activation of MAP3/1 pathway. Additionally, C1QTNF12 increased pMAP3/1-to-MAP3/1 protein expression ratio and enhanced IGF1-induced pTyr-IGF1Rß-to-IGFR1ß and pMAP3/1-to-MAP3/1 protein ratios. Taken together, C1QTNF12 could act directly on proliferation and steroid synthesis and serve as an important factor in in vivo ovarian follicle function, possibly regulating the course of folliculogenesis. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants. Some evidence shows that PAHs could be involved in human obesity. However, little is known about the distribution patterns of PAHs in human adipose tissue (AT) and the role of PAHs on adipogenesis/lipogenesis. The aims of this pilot study were to determine concentrations of 16 PAHs defined as high-priority pollutants in the plasma and adipose tissue of French and Polish bariatric patients, as well as their correlation with body mass index (BMI), plasma and AT adipokines expression levels. We finally investigated the role of naphthalene on cell proliferation, viability, and differentiation in 3T3-L1 preadipocytes. The concentration of most PAHs was similar in the three types of AT and it was significantly higher in AT as compared to plasma, suggesting bioaccumulation. Polish patients had higher PAH levels in AT than French ones. Only the concentration of naphthalene in AT was positively correlated with the BMI and serum or adipose chemerin, adiponectin and resistin expression, in French but not in Polish patients, who had significantly higher BMIs. Moreover, naphthalene exposure increased the cell proliferation of 3T3-L1 preadipocytes and lipogenesis, and increased the expression of genes involved in adipogenesis after cell differentiation. Taken together, PAHs and more particularly naphthalene could be an obesogenic molecule and increase the risk of obesity. [ABSTRACT FROM AUTHOR]

The corpus luteum is a small gland of great importance because its proper functioning determines not only the appropriate course of the estrous/menstrual cycle and embryo implantation, but also the subsequent maintenance of pregnancy. Among the well-known regulators of luteal tissue functions, increasing attention is focused on the role of neuropeptides and adipose tissue hormones—adipokines. Growing evidence points to the expression of these factors in the corpus luteum of women and different animal species, and their involvement in corpus luteum formation, endocrine function, angiogenesis, cells proliferation, apoptosis, and finally, regression. In the present review, we summarize the current knowledge about the expression and role of adipokines, such as adiponectin, leptin, apelin, vaspin, visfatin, chemerin, and neuropeptides like ghrelin, orexins, kisspeptin, and phoenixin in the physiological regulation of the corpus luteum function, as well as their potential involvement in pathologies affecting the luteal cells that disrupt the estrous cycle. [ABSTRACT FROM AUTHOR]

The apelinergic system, which includes the apelin receptor (APJ) as well as its two specific ligands, namely apelin and ELABELA (ELA/APELA/Toddler), have been the subject of many recent studies due to their pleiotropic effects in humans and other animals. Expression of these factors has been investigated in numerous tissues and organs—for example, the lungs, heart, uterus, and ovary. Moreover, a number of studies have been devoted to understanding the role of apelin and the entire apelinergic system in the most important processes in the body, starting from early stages of human life with regulation of placental function and the proper course of pregnancy. Disturbances in the balance of placental processes such as proliferation, apoptosis, angiogenesis, or hormone secretion may lead to specific pregnancy pathologies; therefore, there is a great need to search for substances that would help in their early diagnosis or treatment. A number of studies have indicated that compounds of the apelinergic system could serve this purpose. Hence, in this review, we summarized the most important reports about the role of apelin and the entire apelinergic system in the regulation of placental physiology and pregnancy. [ABSTRACT FROM AUTHOR]

Oocyte maturation is a critical stage in embryo production and female reproduction. The aims of this study were to determine: (i) the mRNA and protein expression of vaspin and its receptor 78-kDa glucose-regulated (GRP78) in porcine cumulus–oocyte complexes (COCs) by real-time PCR and Western blot analysis, respectively, and their localisation by immunofluorescence; and (ii) the effects of vaspin on in vitro oocyte maturation (IVM) and the involvement of mitogen ERK1/2 (MAP3/1)- and AMPKα (PRKAA1)-activated kinases in the studied processes. Porcine COCs were matured in vitro for 22 h or 44 h with vaspin at a dose of 1 ng/mL and nuclear maturation assessed by Hoechst 33342 or DAPI staining and the measurement of progesterone (P4) level in the maturation medium. We showed that vaspin and GRP78 protein expression increased in oocytes and cumulus cells after IVM. Moreover, vaspin enhanced significantly porcine oocyte IVM and P4 concentration, as well as MAP3/1 phosphorylation, while decreasing PRKAA1. Using pharmacological inhibitors of MAP3/1 (PD98059) and PRKAA1 (Compound C), we observed that the effect of vaspin was reversed to the control level by all studied parameters. In conclusion, vaspin, by improving in vitro oocyte maturation via MAP3/1 and PRKAA1 kinase pathways, can be a new factor to improve in vitro fertilisation protocols. [ABSTRACT FROM AUTHOR]

Adipokines influence energy metabolism and have effects on male reproduction, including spermatogenesis and/or Sertoli cell maturation; however, the relationship between these active proteins and androgens in testicular cells is limited. Here, we studied the impact of short-term exposure to flutamide (an anti-androgen that blocks androgen receptors) on the expression of chemerin, apelin, vaspin and their receptors (CCRL2, CMKLR1, GPR1, APLNR, GRP78, respectively) in adult rat testes. Moreover, the levels of expression of lipid metabolism-modulating proteins (PLIN1, perilipin1; TSPO, translocator protein) and intercellular adherens junction proteins (nectin-2 and afadin) were determined in testicular cells. Plasma levels of adipokines, testosterone and cholesterol were also evaluated. Gene expression techniques used included the quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB) and immunohistochemistry (IHC). The androgen-mediated effects observed post-flutamide treatment were found at the gonadal level as chemerin, apelin, and vaspin gene expression alterations at mRNA and protein levels were detected, whereas the cellular targets for these adipokines were recognised by localisation of respective receptors in testicular cells. Plasma concentrations of all adipokines were unchanged, whereas plasma cholesterol content and testosterone level increased after flutamide exposure. Differential distribution of adipokine receptors indicates potential para- or autocrine action of the adipokines within the rat testes. Additionally, changes in the expression of PLIN1 and TSPO, involved in the initial step of testosterone synthesis in Leydig cells, suggest that testicular cells represent a target of flutamide action. Increase in the gene expression of PLIN1 and TSPO and higher total plasma cholesterol content indicates enhanced availability of cholesterol in Leydig cells as a result of androgen-mediated effects of flutamide. Alterations in adherens junction protein expression in the testis confirm the flutamide efficacy in disruption of androgen signalling and presumably lead to impaired para- and autocrine communication, important for proper functioning of adipokines. [ABSTRACT FROM AUTHOR]

Adiponectin is the most abundant plasma adipokine. It mainly derives from white adipose tissue and plays a key role in the control of energy metabolism thanks to its insulin-sensitising, anti-inflammatory, and antiatherogenic properties. In vitro and in vivo evidence shows that adiponectin could also be one of the hormones controlling the interaction between energy balance and fertility in several species, including humans. Indeed, its two receptors—AdipoR1 and AdipoR2—are expressed in hypothalamic–pituitary–gonadal axis and their activation regulates Kiss, GnRH and gonadotropin expression and/or secretion. In male gonads, adiponectin modulates several functions of both somatic and germ cells, such as steroidogenesis, proliferation, apoptosis, and oxidative stress. In females, it controls steroidogenesis of ovarian granulosa and theca cells, oocyte maturation, and embryo development. Adiponectin receptors were also found in placental and endometrial cells, suggesting that this adipokine might play a crucial role in embryo implantation, trophoblast invasion and foetal growth. The aim of this review is to characterise adiponectin expression and its mechanism of action in male and female reproductive tract. Further, since features of metabolic syndrome are associated with some reproductive diseases, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia, endometriosis, foetal growth restriction and ovarian and endometrial cancers, evidence regarding the emerging role of adiponectin in these disorders is also discussed. [ABSTRACT FROM AUTHOR]