TY - JOUR
T1 - Reduced fertility and inability of oocytes to resume meiosis in mice deficient of the Lxr genes
AU - Steffensen, Knut R.
AU - Robertson, Kirsten
AU - Gustafsson, Jan Åke
AU - Andersen, Claus Yding
N1 - Funding Information:
The GW3965 LXR agonist was kindly provided by Dr. Tim Willson (GlaxoSmithKline). This study was supported by the Norwegian Research Council (K.R.S.) and the Swedish Science Council.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2006/8/15
Y1 - 2006/8/15
N2 - Cholesterol precursors act as activators of the nuclear hormone receptor, liver X receptor (LXR). One of these LXR-activating ligands is meiosis activating sterol (MAS), which also induces resumption of meiosis in oocytes from mice in vitro. Whether LXR participates in the regulation of oocyte maturation and whether the expression of either one of the two paralogues of LXR (α and β) affect fertility of mice has, however, not yet been clarified. Female mice lacking Lxra, Lxrb or both genes (Lxra-/-, Lxrb-/- and Lxrab-/-, respectively) conceive less frequently and have significantly fewer pups per litter as compared to wild type mice. Both Lxra and Lxrb mRNA were found to be expressed in mouse oocytes. The relative expression of, in particular, Lxrb was almost two orders of magnitude higher than in liver, brain and testis. A water-soluble LXR agonist caused naked oocytes, but not cumulus enclosed oocytes (CEO), from wild type mice to resume meiosis significantly more often than control oocytes. Follicle stimulating hormone (FSH) is a potent stimulator of meiosis in CEO from wild type mice, but was without effect in mice lacking both Lxr genes. Zymosterol, a MAS active substance, induced resumption of meiosis in oocytes from Lxrab-/- mice, but significantly less effectively than in oocytes from wild type mice. Taken together, LXRs seem to affect ovarian function, suggesting specific roles of cholesterol precursors in regulation of female reproduction.
AB - Cholesterol precursors act as activators of the nuclear hormone receptor, liver X receptor (LXR). One of these LXR-activating ligands is meiosis activating sterol (MAS), which also induces resumption of meiosis in oocytes from mice in vitro. Whether LXR participates in the regulation of oocyte maturation and whether the expression of either one of the two paralogues of LXR (α and β) affect fertility of mice has, however, not yet been clarified. Female mice lacking Lxra, Lxrb or both genes (Lxra-/-, Lxrb-/- and Lxrab-/-, respectively) conceive less frequently and have significantly fewer pups per litter as compared to wild type mice. Both Lxra and Lxrb mRNA were found to be expressed in mouse oocytes. The relative expression of, in particular, Lxrb was almost two orders of magnitude higher than in liver, brain and testis. A water-soluble LXR agonist caused naked oocytes, but not cumulus enclosed oocytes (CEO), from wild type mice to resume meiosis significantly more often than control oocytes. Follicle stimulating hormone (FSH) is a potent stimulator of meiosis in CEO from wild type mice, but was without effect in mice lacking both Lxr genes. Zymosterol, a MAS active substance, induced resumption of meiosis in oocytes from Lxrab-/- mice, but significantly less effectively than in oocytes from wild type mice. Taken together, LXRs seem to affect ovarian function, suggesting specific roles of cholesterol precursors in regulation of female reproduction.
KW - Liver X receptor
KW - Nuclear hormone receptors
KW - Oocyte maturation
KW - Oxysterols
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U2 - 10.1016/j.mce.2006.03.044
DO - 10.1016/j.mce.2006.03.044
M3 - Article
C2 - 16895745
AN - SCOPUS:33746903932
SN - 0303-7207
VL - 256
SP - 9
EP - 16
JO - Molecular and cellular endocrinology
JF - Molecular and cellular endocrinology
IS - 1-2
ER -