Role of the Peroxisome Proliferator-Activated Receptors, Adenosine Monophosphate-Activated Kinase, and Adiponectin in the Ovary

The mechanisms controlling the interaction between energy balance and reproduction are the subject of intensive investigations. The integrated control of these systems is probably a multifaceted phenomenon involving an array of signals governing energy homeostasis, metabolism, and fertility. Two fuel sensors, PPARs, a superfamily of nuclear receptors and the kinase AMPK, integrate energy control and lipid and glucose homeostasis. Adiponectin, one of the adipocyte-derived factors mediate its actions through the AMPK or PPARs pathway. These three molecules are expressed in the ovary, raising questions about the biological actions of fuel sensors in fertility and the use of these molecules to treat fertility problems. This review will highlight the expression and putative role of PPARs, AMPK, and adiponectin in the ovary, particularly during folliculogenesis, steroidogenesis, and oocyte maturation

Ghrelin in Female and Male Reproduction

Ghrelin and one of its functional receptors, GHS-R1a (Growth Hormone Secretagogue Receptor 1a), were firstly studied about 15 years. Ghrelin is a multifunctional peptide hormone that affects several biological functions including food intake, glucose release, cell proliferation… Ghrelin and GHS-R1a are expressed in key cells of both male and female reproductive organs in several species including fishes, birds, and mammals suggesting a well-conserved signal through the evolution and a role in the control of fertility. Ghrelin could be a component of the complex series of nutrient sensors such as adipokines, and nuclear receptors, which regulate reproduction in function of the energy stores. The objective of this paper was to report the available information about the ghrelin system and its role at the level of the hypothalamic-pituitary-gonadal axis in both sexes

Effect of adiponectin on bovine granulosa cell steroidogenesis, oocyte maturation and embryo development

<p>Abstract</p> <p>Background</p> <p>Adiponectin is an adipokine, mainly produced by adipose tissue. It regulates several reproductive processes. The protein expression of the adiponectin system (adiponectin, its receptors, AdipoR1 and AdipoR2 and the APPL1 adaptor) in bovine ovary and its role on ovarian cells and embryo, remain however to be determined.</p> <p>Methods</p> <p>Here, we identified the adiponectin system in bovine ovarian cells and embryo using RT-PCR, immunoblotting and immunohistochemistry. Furthermore, we investigated in vitro the effects of recombinant human adiponectin (10 micro g/mL) on proliferation of granulosa cells (GC) measured by [3H] thymidine incorporation, progesterone and estradiol secretions measured by radioimmunoassay in the culture medium of GC, nuclear oocyte maturation and early embryo development.</p> <p>Results</p> <p>We show that the mRNAs and proteins for the adiponectin system are present in bovine ovary (small and large follicles and corpus luteum) and embryo. Adiponectin, AdipoR1 and AdipoR2 were more precisely localized in oocyte, GC and theca cells. Adiponectin increased IGF-1 10(-8) M-induced GC proliferation (P < 0.01) but not basal or insulin 10(-8) M-induced proliferation. Additionally, adiponectin decreased insulin 10(-8) M-induced, but not basal or IGF-1 10(-8) M-induced secretions of progesterone (P < 0.01) and estradiol (P < 0.05) by GC. This decrease in insulin-induced steroidogenesis was associated with a decrease in ERK1/2 MAPK phosphorylation in GC pre-treated with adiponectin. Finally, addition of adiponectin during in vitro maturation affected neither the percentage of oocyte in metaphase-II nor 48-h cleavage and blastocyst day 8 rates.</p> <p>Conclusions</p> <p>In bovine species, adiponectin decreased insulin-induced steroidogenesis and increased IGF-1-induced proliferation of cultured GC through a potential involvement of ERK1/2 MAPK pathway, whereas it did not modify oocyte maturation and embryo development in vitro.</p

Unraveling the adipose tissue proteome of transition cows through severe negative energy balance

Fat mobilization in high-yielding dairy cows during early lactation occurs to overcome negative energy balance (NEB), caused by insufficient feed intake and the concomitant increased nutritional requirements. For this reason, adipose tissue represents an essential organ for healthy and performant lactation. However, only a few data are known about adipose tissue proteome and its metabolic status during peripartum. The aim of this study was to analyze the differential proteomics profiles of subcutaneous adipose tissue belonging to cows with different NEB scores (low NEB and severe NEB). Both groups were analyzed at three different time points (one month before calving, one and sixteen weeks after calving) that were related to different levels and rates of adipose tissue mobilization. The dataset highlighted the differential expression of the same four key proteins (annexin A2, actin-related protein 10, glyceraldehyde-3-phosphate dehydrogenase, and fatty acid-binding protein) involved in lipid metabolism during all time points and of other 22 proteins typical of the other comparisons among remaining time points. The obtained dataset suggested that the individual variability in adipose tissue metabolism/mobilization/energy availability could be linked to the different outcomes in levels of energy balance and related physical complications among dairy cows during peripartum

Chemerin signalling pathways in human granulosa cells

Chemerin signalling pathways in human granulosa cells. 2. Journées du GdR 3606 Repr

Irisin modulates glucose metabolism and inhibits steroidogenesis in bovine granulosa cells

International audienceIn brief Fertility in the dairy cow is low during the post-partum period of negative energy balance and high plasma irisin concentrations. This study shows irisin modulates granulosa cell glucose metabolism and impairs steroidogenesis. Abstract Fibronectin type III domain-containing 5 (FNDC5) is a transmembrane protein discovered in 2012 that is cleaved to release the adipokine-myokine, irisin. Originally described as an exercise hormone that browns white adipose tissue and increases glucose metabolism, irisin secretion also increases during periods of rapid adipose mobilization, such as the post-partum period in dairy cattle when ovarian activity is suppressed. The effect of irisin on follicle function is unclear and may be species-dependent. In this study, we hypothesized that irisin may compromise granulosa cell function in cattle using a well-established in vitro cell culture model. We detected FNDC5 mRNA and both FNDC5 and cleaved irisin proteins in follicle tissue and in follicular fluid. The abundance of FNDC5 mRNA was increased by the treatment of cells with the adipokine visfatin but not by other adipokines tested. The addition of recombinant irisin to granulosa cells decreased basal and insulin-like growth factor 1- and follicle-stimulating hormone-dependent estradiol and progesterone secretion and increased cell proliferation but had no effect on viability. Irisin decreased GLUT1 , GLUT3 , and GLUT4 mRNA levels in granulosa cells and increased lactate release in the culture medium. The mechanism of action is in part through MAPK3/1 but not Akt, MAPK14, or PRKAA. We conclude that irisin may regulate bovine folliculogenesis by modulating granulosa cell steroidogenesis and glucose metabolism

Chemerin concentration in egg white in layer and broiler hens during the laying period for 2 successive generations

ABSTRACT: The genetic selection progress in layers and broilers makes poultry production one of the fastest growing industries. Objectives of the breeding companies are the stability or the increase in the laying rate and the production of viable chicks. New biomarkers are necessary to improve reproductive and egg performances. Chemerin (Chem) produced by oviduct accumulates in egg white (EW). Here, we hypothesized that EW Chem concentration was dependent on the stage of laying and on the breed (layer vs. broiler). In addition, they could be associated to laying performance and fertility parameters. In breeding companies, we collected during 2 successive generations (G0 (mother) and G1 (daughter)) eggs from 100 layers and 100 broilers hens during 5 d at 3 stages: before, after laying peak and at the end of laying period. For each egg, the EW was sampled to measure Chem concentration by ELISA assay. In each generation at the end of laying period, magnums from oviduct, where the EG is formed, were collected in layers and broilers in order to investigate Chem differential expression by RT-qPCR between both breeds. Chem concentration in EW was dependent on the time of laying period and its profile was differently regulated in layers and broilers. Indeed, it increased at the end of laying in layers whereas it decreased after the laying peak in broilers. At the end of laying period, Chem concentration in EW was almost 2-fold higher in layers than in broilers and this was confirmed in both G0 and G1 generations at the Chem mRNA and protein levels in the magnum. For the 2 successive generations, Chem concentration in EW was negatively correlated with the laying rate and the fertility parameter in broiler hens whereas it was negatively correlated with the egg quality (weight of whole egg and weight of albumen) and positively with the fertility rate at some time of laying in layer hens. Taken together, the Chem concentration in EW could be a potential predictive tool for reproductive parameters in genetic selection

Exploration of chemerin system in human granulosa cells: a new insight for polycystic ovarian syndrome

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Effects of high levels of glucose on the steroidogenesis and the expression of adiponectin receptors in rat ovarian cells

<p>Abstract</p> <p>Background</p> <p>Reproductive dysfunction in the diabetic female rat is associated with altered folliculogenesis and steroidogenesis. However, the molecular mechanisms involved in the reduction of steroid production have not been described. Adiponectin is an adipocytokine that has insulin-sensitizing actions including stimulation of glucose uptake in muscle and suppression of glucose production in liver. Adiponectin acts via two receptor isoforms – AdipoR1 and AdipoR2 – that are regulated by hyperglycaemia and hyperinsulinaemia in liver and muscle. We have recently identified AdipoR1 and AdipoR2 in rat ovary. However, their regulation in ovaries of diabetic female rat remains to be elucidated.</p> <p>Methods</p> <p>We incubated rat primary granulosa cells in vitro with high concentrations of glucose (5 or 10 g/l) + or - FSH (10-8 M) or IGF-1 (10-8 M), and we studied the ovaries of streptozotocin-induced diabetic rats (STZ) in vivo. The levels of oestradiol and progesterone in culture medium and serum were measured by RIA. We used immunoblotting to assay key steroidogenesis factors (3beta HSD, p450scc, p450 aromatase, StAR), and adiponectin receptors and various elements of signalling pathways (MAPK ERK1/2 and AMPK) in vivo and in vitro. We also determined cell proliferation by [3H] thymidine incorporation.</p> <p>Results</p> <p>Glucose (5 or 10 g/l) impaired the in vitro production in rat granulosa cells of both progesterone and oestradiol in the basal state and in response to FSH and IGF-1 without affecting cell proliferation and viability. This was associated with substantial reductions in the amounts of 3beta HSD, p450scc, p450 aromatase and StAR proteins and MAPK ERK1/2 phosphorylation. In contrast, glucose did not affect the abundance of AdipoR1 or AdipoR2 proteins. In vivo, as expected, STZ treatment of rats caused hyperglycaemia and insulin, adiponectin and resistin deficiencies. Plasma progesterone and oestradiol levels were also reduced in STZ rats. However, the amounts of 3beta HSD and p450 aromatase were the same in STZ rat ovary and controls, and the amounts of StAR and p450scc were higher. Streptozotocin treatment did not affect adiponectin receptors in rat ovary but it increased AMPK phosphorylation without affecting MAPK ERK1/2 phosphorylation.</p> <p>Conclusion</p> <p>High levels of glucose decrease progesterone and oestradiol production in primary rat granulosa cells and in STZ-treated rats. However, the mechanism that leads to reduced ovarian steroid production seems to be different. Furthermore, adiponectin receptors in ovarian cells are not regulated by glucose.</p