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Updated: Apr 3, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Identification of the Functions of Liver X Receptor-β in Sertoli Cells Using a Targeted Expression-Rescue Model
Salwan Maqdasy1, Fatim-Zohra El Hajjaji1, Marine Baptissart1
1Department of Génétique Reproduction et Développement (GReD) (S.M., F.-Z.E.H., M.B., A.O., F.B., A.T., I.T., D.V., J.-M.A.L., S.B.), Université Blaise Pascal, Centre de Recherche en Nutrition Humaine d'Auvergne (S.M., F.-Z.E.H., M.B., A.O., F.B., A.T., D.V., J.-M.A.L., S.B.), and Department of Assistance Médicale à la Procréation (F.B.), CECOS, Centre Hospitalier Universitaire Clermont Ferrand, Centre Hospitalier Universitaire Estaing, F-63000 Clermont-Ferrand, France; Centre National de la Recherche Scientifique (S.M., F.-Z.E.H., M.B., A.O., F.B., A.T., I.T., D.V., J.-M.A.L., S.B.) and INSERM (S.M., F.-Z.E.H., M.B., A.O., F.B., A.T., I.T., D.V., J.-M.A.L., S.B.), Unité Mixte de Recherche 6293, GReD, F-63177 Aubiere, France; Center for Diagnostics and Therapeutics (E.V.), Georgia State University, Atlanta, Georgia 30302-4010; Veterans Affairs Medical Center (E.V.), Decatur, Georgia 30033; Service d'Endocrinologie, Diabétologie, et Maladies Métaboliques (S.M., I.T.), Hôpital Gabriel Montpied, F-63003 Clermont-Ferrand, France; and Service de Médecine Nucléaire (S.M.), Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
Abstract:
Liver X receptors (LXRs) are key regulators of lipid homeostasis and are involved in multiple testicular functions. The Lxrα(-/-);Lxrβ(-/-) mice have illuminated the roles of both isoforms in maintenance of the epithelium in the seminiferous tubules, spermatogenesis, and T production. The requirement for LXRβ in Sertoli cells have been emphasized by early abnormal cholesteryl ester accumulation in the Lxrβ(-/-) and Lxrα(-/-);Lxrβ(-/-) mice. Other phenotypes, such as germ cell loss and hypogonadism, occur later in life in the Lxrα(-/-);Lxrβ(-/-) mice. Thus, LXRβ expression in Sertoli cells seems to be essential for normal testicular physiology. To decipher the roles of LXRβ within the Sertoli cells, we generated Lxrα(-/-);Lxrβ(-/-):AMH-Lxrβ transgenic mice, which reexpress Lxrβ in Sertoli cells in the context of Lxrα(-/-);Lxrβ(-/-) mice. In addition to lipid homeostasis, LXRβ is necessary for maintaining the blood-testis barrier and the integrity of the germ cell epithelium. LXRβ is also implicated in the paracrine action of Sertoli cells on Leydig cells to modulate T synthesis. The Lxrα(-/-);Lxrβ(-/-) and Lxrα(-/-);Lxrβ(-/-):AMH-Lxrβ mice exhibit lipid accumulation in germ cells after the Abcg8 down-regulation, suggesting an intricate LXRβ-dependent cooperation between the Sertoli cells and germ cells to ensure spermiogenesis. Further analysis revealed also peritubular smooth muscle defects (abnormal lipid accumulation and disorganized smooth muscle actin) and spermatozoa stagnation in the seminiferous tubules. Together the present work elucidates specific roles of LXRβ in Sertoli cell physiology in vivo beyond lipid homeostasis.
