title: Aging does not affect spermatogenic recovery after experimentally induced injury in mice.
abstract: Testes in aging mammals undergo a variety of age-related changes, such as reduction of size, lower sperm output, an increase in abnormal forms of sperm, and endocrine malfunctions. It has been suggested that the spermatogenic defects are due to loss and dysfunction of spermatogonial stem cells as well as deterioration of the tubule microenvironment. In the present study, we explore the depletion and recovery of spermatogenesis in young (3 month) and old (12 month) mice exposed to cooling, X-irradiation (5 Gy) or cytotoxic treatment using Busulfan (40 mg/kg). We aim to determine a potential age-related change of vulnerability to gonadotoxic treatments by describing the intensity of spermatogenic depletion and the degree of spermatogenic recolonization with qualitative and quantitative parameters on organ weights and histological parameters at two time points (2 weeks, depletion; 6 weeks, recovery). Our data reveal specific acute effects of cooling on multinucleation of germ cells but no other severe injury. Irradiation and Busulfan-treatment exerted the expected depletional wave of germ cells leading to severe testicular injury and spermatogenic failure. The recovery of spermatogenesis occurred in both treatment groups and both age groups to a similar extent. We therefore noted no prominent age-related differences in spermatogenic depletion and recovery in any treatment group. We conclude that in both age groups, the remaining spermatogonial stem cells are capable to induce spermatogenic recovery and the aging tubule microenvironment at 1 year has not become more vulnerable to irradiation, Busulfan-treatment or testicular cooling.
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of Medicine, W952 Biomedical Science Towers, 3500 Terrace Street, Pittsburgh 15261, Pennsylvania, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Ehmcke
authors.forename: Bhavika
authors.initials: B
authors.lastname: Joshi
authors.forename: Scott D
authors.initials: SD
authors.lastname: Hergenrother
authors.forename: Stefan
authors.initials: S
authors.lastname: Schlatt
mesh_terms: D000375:Aging / Q000502:physiology*; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D002066:Busulfan / Q000633:toxicity; D002467:Cell Nucleus / Q000648:ultrastructure; D003080:Cold Temperature / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D012708:Sertoli Cells / Q000502:physiology; D013076:Sperm Count; D013087:Spermatids / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013737:Testis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014965:X-Rays / Q000009:adverse effects
chemical_list: D000477:Alkylating Agents; D002066:Busulfan