scholarly journals PPARs and Female Reproduction: Evidence from Genetically Manipulated Mice

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Jichun Yang ◽  
Lihong Chen ◽  
Xiaoyan Zhang ◽  
Yunfeng Zhou ◽  
Dongjuan Zhang ◽  
...  

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors controlling many important physiological processes, including lipid and glucose metabolism, energy homeostasis, inflammation, as well as cell proliferation and differentiation. In the past decade, intensive study of PPARs has shed novel insight into prevention and treatment of dyslipidemia, insulin resistance, and type 2 diabetes. Recently, a large body of research revealed that PPARs are also functionally expressed in reproductive organs and various parts of placenta during pregnancy, which strongly suggests that PPARs might play a critical role in reproduction and development, in addition to their central actions in energy homeostasis. In this review, we summarize recent findings elucidating the role of PPARs in female reproduction, with particular focus on evidence from gene knockout and transgenic animal model study.

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Maurizio Vitti ◽  
Giovanna Di Emidio ◽  
Michela Di Carlo ◽  
Gaspare Carta ◽  
Andrea Antonosante ◽  
...  

Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed.


2002 ◽  
Vol 22 (8) ◽  
pp. 2607-2619 ◽  
Author(s):  
Taro E. Akiyama ◽  
Shuichi Sakai ◽  
Gilles Lambert ◽  
Christopher J. Nicol ◽  
Kimihiko Matsusue ◽  
...  

ABSTRACT Disruption of the peroxisome proliferator-activated receptor γ (PPARγ) gene causes embryonic lethality due to placental dysfunction. To circumvent this, a PPARγ conditional gene knockout mouse was produced by using the Cre-loxP system. The targeted allele, containing loxP sites flanking exon 2 of the PPARγ gene, was crossed into a transgenic mouse line expressing Cre recombinase under the control of the alpha/beta interferon-inducible (MX) promoter. Induction of the MX promoter by pIpC resulted in nearly complete deletion of the targeted exon, a corresponding loss of full-length PPARγ mRNA transcript and protein, and marked reductions in basal and troglitazone-stimulated expression of the genes encoding lipoprotein lipase, CD36, LXRα, and ABCG1 in thioglycolate-elicited peritoneal macrophages. Reductions in the basal levels of apolipoprotein E (apoE) mRNA in macrophages and apoE protein in total plasma and high-density lipoprotein (HDL) were also observed in pIpC-treated PPARγ-MXCre+ mice. Basal cholesterol efflux from cholesterol-loaded macrophages to HDL was significantly reduced after disruption of the PPARγ gene. Troglitazone selectively inhibited ABCA1 expression (while rosiglitazone, ciglitazone, and pioglitazone had little effect) and cholesterol efflux in both PPARγ-deficient and control macrophages, indicating that this drug can exert paradoxical effects on cholesterol homeostasis that are independent of PPARγ. Together, these data indicate that PPARγ plays a critical role in the regulation of cholesterol homeostasis by controlling the expression of a network of genes that mediate cholesterol efflux from cells and its transport in plasma.


PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Caroline I. Schnegg ◽  
Mike E. Robbins

Peroxisome proliferator-activated receptors (PPARα,δ, andγ) are ligand-activated transcription factors that regulate a wide range of cellular processes, including inflammation, proliferation, differentiation, metabolism, and energy homeostasis. All three PPAR subtypes have been identified in the central nervous system (CNS) of rodents. While PPARαand PPARγare expressed in more restricted areas of the CNS, PPARδis ubiquitously expressed and is the predominant subtype. Although data regarding PPARδare limited, studies have demonstrated that administration of PPARδagonists confers neuroprotection following various acute and chronic injuries to the CNS, such as stroke, multiple sclerosis, and Alzheimer's disease. The antioxidant and anti-inflammatory properties of PPARδagonists are thought to underly their neuroprotective efficacy. This review will focus on the putative neuroprotective benefits of therapeutically targeting PPARδin the CNS, and specifically, highlight the antioxidant and anti-inflammatory functions of PPARδagonists.


PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Anne Bugge ◽  
Susanne Mandrup

The peroxisome proliferator-activated receptors (PPARs) are central regulators of fat metabolism, energy homeostasis, proliferation, and inflammation. The three PPAR subtypes, PPAR, /, and activate overlapping but also very different target gene programs. This review summarizes the insights into PPAR subtype-specific transactivation provided by genome-wide studies and discusses the recent advances in the understanding of the molecular mechanisms underlying PPAR subtype specificity with special focus on the regulatory role of AF-1.


2012 ◽  
Vol 50 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Anna Maria Di Blasio ◽  
Michele Vignali ◽  
Davide Gentilini

Endocannabinoids are endogenous ligands of cannabinoid, vanilloid and peroxisome proliferator-activated receptors that activate multiple signal transduction pathways. Together with their receptor and the enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system that has been recently shown to play, in humans, an important role in modulating several central and peripheral functions including reproduction. Given the relevance of the system, drugs that are able to interfere with the activity of endocannabinoids are currently considered as candidates for the treatment of various diseases. In this review, we will summarise the current knowledge regarding the effects of endocannabinoids in female reproductive organs. In particular, we will focus on some newly reported mechanisms that can affect endometrial plasticity both in physiological and in pathological conditions.


Endocrines ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 22-34
Author(s):  
Yao Ye ◽  
Peng Lin ◽  
Junyan Zhu ◽  
Udo Jeschke ◽  
Viktoria von Schönfeldt

Among prostaglandins, Prostaglandin E2 (PGE2) (PGE2) is considered especially important for decidualization, ovulation, implantation and pregnancy. Four major PGE2 receptor subtypes, EP1, EP2, EP3, EP4, as well as peroxisome proliferator-activated receptors (PPARs), mediate various PGE2 effects via their coupling to distinct signaling pathways. This review summarizes up-to-date literatures on the role of prostaglandin E2 receptors in female reproduction, which could provide a broad perspective to guide further research in this field. PGE2 plays an indispensable role in decidualization, ovulation, implantation and pregnancy. However, the precise mechanism of Prostaglandin E2 (EP) receptors in the female reproductive system is still limited. More investigations should be performed on the mechanism of EP receptors in the pathological states, and the possibility of EP agonists or antagonists clinically used in improving reproductive disorders.


2006 ◽  
Vol 6 ◽  
pp. 1770-1782 ◽  
Author(s):  
Emanuela Esposito ◽  
Salvatore Cuzzocrea ◽  
Rosaria Meli

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. Three isotypes of PPARs have been identified: alpha, beta/delta, and gamma, encoded by different genes and distributed in various tissues. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and, thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert anti-inflammatory effects by inhibiting the induction of proinflammatory cytokines, adhesion molecules, and extracellular matrix proteins, or by stimulating the production of anti-inflammatory molecules. Moreover, PPARs modulate the proliferation, differentiation, and survival of immune cells. This review presents the current state of knowledge regarding the involvement of PPARs in the control of inflammatory response, and their potential therapeutic applications in several types of shock, as well as hemorrhagic, septic, and nonseptic shock.


PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Tsuyoshi Goto ◽  
Nobuyuki Takahashi ◽  
Shizuka Hirai ◽  
Teruo Kawada

Several herbal plants improve medical conditions. Such plants contain many bioactive phytochemicals. Terpenoids (also called “isoprenoids”) constitute one of the largest families of natural products accounting for more than 40,000 individual compounds of both primary and secondary metabolisms. In particular, terpenoids are contained in many herbal plants, and several terpenoids have been shown to be available for pharmaceutical applications, for example, artemisinin and taxol as malaria and cancer medicines, respectively. Various terpenoids are contained in many plants for not only herbal use but also dietary use. In this paper, we describe several bioactive terpenoids contained in herbal or dietary plants, which can modulate the activities of ligand-dependent transcription factors, namely, peroxisome proliferator-activated receptors (PPARs). Because PPARs are dietary lipid sensors that control energy homeostasis, daily eating of these terpenoids might be useful for the management for obesity-induced metabolic disorders, such as type 2 diabetes, hyperlipidemia, insulin resistance, and cardiovascular diseases.


2021 ◽  
Author(s):  
Nathalie di Clemente ◽  
Chrystèle Racine ◽  
Alice Pierre ◽  
Joëlle Taieb

Abstract Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance, was shown to be synthesized by the ovary in the eighties. This article reviews the main findings of the past 20 years on the regulation of the expression of AMH and its specific receptor AMHR2 by granulosa cells, the mechanism of action of AMH, the different roles it plays in the reproductive organs, its clinical utility and its involvement in the principal pathological conditions affecting women. The findings in respect of regulation tell us that AMH and AMHR2 expression is mainly regulated by Bone Morphogenetic Proteins, gonadotropins and estrogens. It has now been established that AMH regulates the different steps of folliculogenesis and that it has neuroendocrine effects. On the other hand, the importance of serum AMH as a reliable marker of ovarian reserve and as a useful tool in the prediction of the polycystic ovary syndrome (PCOS) and primary ovarian failure has also been acknowledged. Last but not least, a large body of evidence points to the involvement of AMH in the pathogenesis of PCOS.


Diabetes ◽  
2003 ◽  
Vol 52 (9) ◽  
pp. 2249-2259 ◽  
Author(s):  
P. J. Larsen ◽  
P. B. Jensen ◽  
R. V. Sorensen ◽  
L. K. Larsen ◽  
N. Vrang ◽  
...  

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