title: Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice.
abstract: The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Diane
authors.initials: D
authors.lastname: Rebourcet
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Junxi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Lyndsey
authors.initials: L
authors.lastname: Cruickshanks
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Smith
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Milne
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Anuruddika
authors.initials: A
authors.lastname: Fernando
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wallace
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Calum D
authors.initials: CD
authors.lastname: Gray
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Rod T
authors.initials: RT
authors.lastname: Mitchell
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Shaughnessy
authors.affiliation: Medical Research Council Centre for Reproductive Health (D.R., J.W., L.C., S.E.S., L.M., A.F., R.T.M., L.B.S.), University/BHF Centre for Cardiovascular Science (J.W., P.W.F.H.), and Clinical Research Imaging Centre (C.D.G.), University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom; Department of Orthopaedics (R.J.W.), University of Edinburgh, Edinburgh Eh16 4SB, United Kingdom; and Institute of Biodiversity, Animal Health, and Comparative Medicine (P.J.O.), University of Glasgow, Garscube Campus, Glasgow G61 1QH, United Kingdom.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Smith
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006062:Gonadotropins / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D055806:Microvessels / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000097:blood* / Q000378:metabolism*
chemical_list: D006062:Gonadotropins; D013739:Testosterone