title: Loss of PI3K p110αin the Adipose Tissue Results in Infertility and Delayed Puberty Onset in Male Mice.
abstract: Deletion of PI3K catalytic subunit p110αin adipose tissue (aP2-Cre/p110αflx/flx,α-/- hereafter) results in increased adiposity, glucose intolerance, and liver steatosis. Because this endocrine organ releases hormones like leptin, which are important in reproductive physiology, we investigated the reproductive phenotype ofα-/- males. Compared to controls,α-/- males displayed delayed onset of puberty accompanied by a reduction in plasma LH levels and testicular weight. At postnatal day 30,α-/- mice exhibited normal body weight but elevated fasted plasma leptin levels. Testicular leptin gene expression was increased, whereas expression of the cholesterol transporter StAR and of P450 cholesterol side chain cleavage enzyme was decreased. Adultα-/- males were infertile and exhibited hyperandrogenemia with normal basal LH, FSH, and estradiol levels. However, neither sperm counts nor sperm motility was different between genotypes. The mRNA levels of leptin and of 17-beta-dehydrogenase 3, and enzyme important for testosterone production, were significantly higher in the testis of adultα-/- males. The mRNA levels of ERα, an important regulator of intratesticular steroidogenesis, were lower in the testis of adult and peripubertalα-/- males. We propose that chronic hyperleptinemia contributes to the negative impact that disrupting PI3K signaling in adipocytes has on puberty onset, steroidogenesis, and fertility in males.
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, NY, USA.
authors.forename: Victoria L Boughton
authors.initials: VL
authors.lastname: Nelson
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, NY, USA; Graduate Program in Neuroscience, State University of New York at Stony Brook, Stony Brook, NY, USA.
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Negrón
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, NY, USA.
authors.forename: Inefta
authors.initials: I
authors.lastname: Reid
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, NY, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Thomas
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, NY, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, NY, USA; Department of Veterans Affairs Medical Center, Northport, NY, USA.
authors.forename: Richard Z
authors.initials: RZ
authors.lastname: Lin
authors.affiliation: Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, NY, USA.
authors.forename: Maricedes
authors.identifier: 0000-0003-0841-4032
authors.initials: M
authors.lastname: Acosta-Martínez
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D058534:Class I Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics*; D005640:Follicle Stimulating Hormone / Q000097:blood; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020738:Leptin / Q000097:blood / Q000235:genetics; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011628:Puberty, Delayed / Q000097:blood / Q000235:genetics* / Q000473:pathology; D013076:Sperm Count; D013081:Sperm Motility / Q000235:genetics; D013739:Testosterone / Q000096:biosynthesis
chemical_list: D020738:Leptin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015067:17-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+)); C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases