Levels of liver X receptors in testicular biopsies of patients with azoospermia

Rondanino, Christine; Ouchchane, Lemlih; Chauffour, Candice; Marceau, Geoffroy; Déchelotte, P.; Sion, Benoı̂t; Pons-Rejraji, Hanae; Janny, L.; Volle, David H.; Lobaccaro, Jean-Marc A.; Brugnon, Florence

doi:10.1016/j.fertnstert.2014.04.033

Cited by 12 publications

(17 citation statements)

References 32 publications

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“…This transcriptional factor is expressed in Sertoli and germ cells, and was found deregulated in testicular biopsies of patients with azoospermia 65 . Consistently, its ligands (sterols) have been up-regulated in the case of oxidative stress and cell death 66 .…”

Section: Discussionmentioning

confidence: 99%

Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction

Buñay

Larriba

Moreno

et al. 2017

Sci Rep

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Humans are environmentally exposed not only to single endocrine-disrupting chemicals (EDCs) but to mixtures that affect their reproductive health. In reproductive tissues, microRNAs (miRNAs) are emerging as key targets of EDCs. Here, we analysed changes in the testis “miRNome” (and their biogenesis mechanism) in chronically exposed adult mice to a cocktail of five EDCs containing 0.3 mg/kg-body weight (BW)/day of each phthalate (DEHP, DBP, BBP) and 0.05 mg/kg-BW/day of each alkylphenol (NP, OP), from conception to adulthood. The testis “miRNome” was characterised using next-generation sequencing (NGS). Expression levels of genes involved in miRNA biogenesis were measured by RT-qPCR, as well as several physiological and cytological parameters. We found two up-regulated, and eight down-regulated miRNAs and thirty-six differentially expressed isomiRs along with an over-expression of Drosha, Adar and Zcchc11. A significant decrease of intratesticular estradiol but not testosterone was detected. Functional analysis showed altered spermatogenesis, germ cell apoptosis and negative correlation of miR-18a-5p with Nr1h2 involved in the deregulation of the steroidogenesis pathway. Here, we present the first association between miRNA/isomiRs deregulation, their mechanisms of biogenesis and histopathological and hormonal alterations in testes of adult mice exposed to a mixture of low-dose EDCs, which can play a role in male infertility.

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Section: Discussionmentioning

confidence: 99%

Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction

Buñay

Larriba

Moreno

et al. 2017

Sci Rep

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“…This is associated with a decrease of germ cell proliferation rate. Interestingly, it was shown that men with azoospermia present a significant decrease of Lxr β expression within the testis associated with fewer proliferating germ cells ( 93 ). Mice deficient for both LXRs isoforms present progressive testicular degeneration associated with germ cell depletion.…”

Section: The Testis Cholesterol Homeostasismentioning

confidence: 99%

“…This could explain the complete loss of germ cells in these mice and thus infertility. Recently, the implication of LXRs in the physiopathology of defective spermatogenesis in non-obstructive azoospermia (NOA) patients was investigated ( 93 ). Indeed, abnormalities observed in NOA patients look like those observed in Lxr −/− mice.…”

Section: The Testis Cholesterol Homeostasismentioning

confidence: 99%

Cholesterol: A Gatekeeper of Male Fertility?

et al. 2018

Self Cite

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Cholesterol is essential for mammalian cell functions and integrity. It is an important structural component maintaining the permeability and fluidity of the cell membrane. The balance between synthesis and catabolism of cholesterol should be tightly regulated to ensure normal cellular processes. Male reproductive function has been demonstrated to be dependent on cholesterol homeostasis. Here we review data highlighting the impacts of cholesterol homeostasis on male fertility and the molecular mechanisms implicated through the signaling pathways of some nuclear receptors.

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“…LXRα and LXRβ are expressed in the mouse and human testes [17,73,74] and an understanding of testicular LXRs has originated from studies using knockout mice where either LXR isoform ( Lxrα -/- or Lxrβ -/-) or both LXR isoforms ( Lxrαβ -/-) are ablated [38,68]. In the mouse, Leydig cells express mainly LXRα, and Sertoli cells express LXRβ, whilst both isoforms are expressed in germ cells [18].…”

Section: Lxrs Are Important For Maintenance Of Male Fertilitymentioning

confidence: 99%

Liver X Receptors and Male (In)fertility

Jarvis

Williamson

Bevan

2019

IJMS

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Liver X receptors (LXRs) are ligand-dependent transcription factors acting as ‘cholesterol sensors’ to regulate lipid homeostasis in cells. The two isoforms, LXRα (NR1H3) and LXRβ (NR1H2), are differentially expressed, with the former expressed predominantly in metabolically active tissues and the latter more ubiquitously. Both are activated by oxidised cholesterol metabolites, endogenously produced oxysterols. LXRs have important roles in lipid metabolism and inflammation, plus a number of newly emerging roles. They are implicated in regulating lipid balance in normal male reproductive function and may provide a link between male infertility and lipid disorders and/or obesity. Studies from Lxr knockout mouse models provide compelling evidence to support this. More recently published data suggest distinct and overlapping roles of the LXR isoforms in the testis and recent evidence of a role for LXRs in human male fertility. This review summarises the current literature and explores the likely link between LXR, lipid metabolism and male fertility as part of a special issue on Liver X receptors in International Journal of Molecular Sciences.

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Levels of liver X receptors in testicular biopsies of patients with azoospermia

Cited by 12 publications

References 32 publications

Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction

Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction

Cholesterol: A Gatekeeper of Male Fertility?

Liver X Receptors and Male (In)fertility

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