title: Rhox13 is required for a quantitatively normal first wave of spermatogenesis in mice.
abstract: We previously described a novel germ cell-specific X-linked reproductive homeobox gene (Rhox13) that is upregulated at the level of translation in response to retinoic acid (RA) in differentiating spermatogonia and preleptotene spermatocytes. We hypothesize that RHOX13 plays an essential role in male germ cell differentiation, and have tested this by creating a Rhox13 gene knockout (KO) mouse. Rhox13 KO mice are born in expected Mendelian ratios, and adults have slightly reduced testis weights, yet a full complement of spermatogenic cell types. Young KO mice (at ~7-8 weeks of age) have a ≈50% reduction in epididymal sperm counts, but numbers increased to WT levels as the mice reach ~17 weeks of age. Histological analysis of testes from juvenile KO mice reveals a number of defects during the first wave of spermatogenesis. These include increased apoptosis, delayed appearance of round spermatids and disruption of the precise stage-specific association of germ cells within the seminiferous tubules. Breeding studies reveal that both young and aged KO males produce normal-sized litters. Taken together, our results indicate that RHOX13 is not essential for mouse fertility in a controlled laboratory setting, but that it is required for optimal development of differentiating germ cells and progression of the first wave of spermatogenesis.
authors.affiliation: Department of Anatomy and Cell BiologyBrody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Busada
authors.affiliation: Department of Anatomy and Cell BiologyBrody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Velte
authors.affiliation: Department of Anatomy and Cell BiologyBrody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Serra
authors.affiliation: Department of Anatomy and Cell BiologyBrody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cook
authors.affiliation: Department of Anatomy and Cell BiologyBrody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Niedenberger
authors.affiliation: Gamete Biology GroupReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Willis
authors.affiliation: Gamete Biology GroupReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Eugenia H
authors.initials: EH
authors.lastname: Goulding
authors.affiliation: Gamete Biology GroupReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Eddy
authors.affiliation: Department of Anatomy and Cell BiologyBrody School of Medicine at East Carolina University, Greenville, North Carolina, USA East Carolina Diabetes and Obesity Institute Brody School of Medicine at East Carolina UniversityGreenville, North Carolina, USA geyerc@ecu.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Geyer
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004822:Epididymis / Q000166:cytology*; D005260:Female; D005306:Fertilization / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013090:Spermatocytes / Q000166:cytology*; D013091:Spermatogenesis / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C532798:Rhox13 protein, mouse