Emerging roles for LXRs and LRH-1 in female reproduction

Mouzat, Kévin; Baron, Silvère; Marceau, Geoffroy; Caira, Françoise; Sapin, Vincent; Volle, David H.; Lumbroso, Serge; Lobaccaro, Jean‐Marc

doi:10.1016/j.mce.2012.06.009

Cited by 29 publications

(24 citation statements)

References 133 publications

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“…Lipid metabolism also plays an evolutionarily conserved role during RS embryonic development and fertility (Barton et al, 2016; Sano et al, 2005). Cholesterol and β-oxidation of fatty acids are essential for meiosis, embryo development, and uterus function in both mice and humans (Downs et al, 2009; Dunning et al, 2010; Mouzat et al, 2013; Seli et al, 2014). In D. melanogaster , female feeding behavior, lipid accumulation in the oocyte, and diet nutrient coordination, lipid metabolism and oocyte development are controlled by the Ecdysone receptor (EcR) (Sieber and Spradling, 2015).…”

Section: Introductionmentioning

confidence: 99%

A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs

Zhang

Guo

Guerrero‐Hernández

et al. 2018

Preprint

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Understanding how stem cells and their progeny maintain and regenerate reproductive organs is of fundamental importance. The freshwater planarian Schmidtea mediterranea provides an attractive system to study these processes because its hermaphroditic reproductive system (RS) arises post-embryonically and when lost can be fully and functionally regenerated from the proliferation and regulation of experimentally accessible stem and progenitor cells. By controlling the function of a nuclear hormone receptor gene (nhr-1), we established conditions in which to study the formation, maintenance and regeneration of both germline and somatic tissues of the planarian RS. We found that nhr-1(RNAi) not only resulted in the gradual degeneration and complete loss of the adult hermaphroditic RS, but also in the significant downregulation of a large cohort of genes associated with lipid metabolism. One of these, Smed-acs-1, a homologue of Acyl-CoA synthetase, was indispensable for the development, maintenance and regeneration of the RS, but not for the homeostasis or regeneration of other somatic tissues. Remarkably, supplementing nhr-1(RNAi) animals with either bacterial Acyl-CoA synthetase or the lipid metabolite Acetyl-CoA rescued the phenotype restoring the maintenance and function of the hermaphroditic RS. Our findings uncovered a likely evolutionarily conserved role for nuclear hormone receptors and lipid metabolism in the regulation of stem and progenitor cells required for the long-term maintenance and regeneration of animal reproductive organs, tissues and cells.

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Section: Introductionmentioning

confidence: 99%

A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs

Zhang

Guo

Guerrero‐Hernández

et al. 2018

Preprint

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“…Many literatures have elucidated the function of Lrh1 / Nr5a2 / FTF / CYP7A via experimental studies [21-25]. …”

Section: Discussionmentioning

confidence: 99%

Identification of transcription factors and single nucleotide polymorphisms of Lrh1 and its homologous genes in Lrh1-knockout pancreas of mice

et al. 2014

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BackgroundTo identify transcription factors (TFs) and single nucleotide polymorphisms (SNPs) of Lrh1 (also named Nr5a2) and its homologous genes in Lrh1-knockout pancreas of mice.MethodsThe RNA-Seq data GSE34030 were downloaded from Gene Expression Omnibus (GEO) database, including 2 Lrh1 pancreas knockout samples and 2 wild type samples. All reads were processed through TopHat and Cufflinks package to calculate gene-expression level. Then, the differentially expressed genes (DEGs) were identified via non-parametric algorithm (NOISeq) methods in R package, of which the homology genes of Lrh1 were identified via BLASTN analysis. Furthermore, the TFs of Lrh1 and its homologous genes were selected based on TRANSFAC database. Additionally, the SNPs were analyzed via SAM tool to record the locations of mutant sites.ResultsTotal 15683 DEGs were identified, of which 23 was Lrh1 homology genes (3 up-regulated and 20 down-regulated). Fetoprotein TF (FTF) was the only TF of Lrh1 identified and the promoter-binding factor of FTF was CYP7A. The SNP annotations of Lrh1 homologous genes showed that 92% of the mutation sites were occurred in intron and upstream. Three SNPs of Lrh1 were located in intron, while 1819 SNPs of Phkb were located in intron and 1343 SNPs were located in the upstream region.ConclusionFTF combined with CYP7A might play an important role in Lrh1 regulated pancreas-specific transcriptional network. Furthermore, the SNPs analysis of Lrh1 and its homology genes provided the candidate mutant sites that might affect the Lrh1-related production and secretion of pancreatic fluid.

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“…Because of their roles in the regulation of numerous metabolic functions, LXRs could represent part of the molecular link between lipid disorders and infertility. Thus, many arguments led to deeply investigating LXRs in female reproductive function, namely: (1) the close relationship between cholesterol and ovarian physiology [4,10,11]; (2) the increasing body of literature describing the novel biological roles of LXRs in the regulation of steroid synthesis and inflammation, two processes necessary for follicle maturation and ovulation [12,13,14,15,16,17]; (3) the fact that oxysterols, which are the physiological ligands [18], play a potential role in the maturation of the oocytes [19,20]; (4) and the role of LXRs in spermatogenesis suggests common germ cell pathways regulated by LXRs [7,14,17]. …”

Section: Introductionmentioning

confidence: 99%

Liver X Receptors: A Possible Link between Lipid Disorders and Female Infertility

Dallel

Tauveron

Brugnon

et al. 2018

IJMS

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A close relationship exists between cholesterol and female reproductive physiology. Indeed, cholesterol is crucial for steroid synthesis by ovary and placenta, and primordial for cell structure during folliculogenesis. Furthermore, oxysterols, cholesterol-derived ligands, play a potential role in oocyte maturation. Anomalies of cholesterol metabolism are frequently linked to infertility. However, little is known about the molecular mechanisms. In parallel, increasing evidence describing the biological roles of liver X receptors (LXRs) in the regulation of steroid synthesis and inflammation, two processes necessary for follicle maturation and ovulation. Both of the isoforms of LXRs and their bona fide ligands are present in the ovary. LXR-deficient mice develop late sterility due to abnormal oocyte maturation and increased oocyte atresia. These mice also have an ovarian hyper stimulation syndrome in response to gonadotropin stimulation. Hence, further studies are necessary to explore their specific roles in oocyte, granulosa, and theca cells. LXRs also modulate estrogen signaling and this could explain the putative protective role of the LXRs in breast cancer growth. Altogether, clinical studies would be important for determining the physiological relevance of LXRs in reproductive disorders in women.

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Emerging roles for LXRs and LRH-1 in female reproduction

Cited by 29 publications

References 133 publications

A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs

A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs

Identification of transcription factors and single nucleotide polymorphisms of Lrh1 and its homologous genes in Lrh1-knockout pancreas of mice

Liver X Receptors: A Possible Link between Lipid Disorders and Female Infertility

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