title: Testicular somatic cells, not gonocytes, are the major source of functional activin A during testis morphogenesis.
abstract: Proper development of the seminiferous tubules (or testis cords in embryos) is critical for male fertility. Sertoli cells, somatic components of the seminiferous tubules, serve as nurse cells to the male germline, and thus their numbers decide the quantity of sperm output in adulthood. We previously identified activin A, the protein product of the activin βA (Inhba) gene, as a key regulator of murine Sertoli cell proliferation and testis cord expansion during embryogenesis. Although our genetic studies implicated fetal Leydig cells as the primary producers of testicular activin A, gonocytes are another potential source. To investigate the relative contribution of gonocyte-derived activin A to testis morphogenesis, we compared testis development in the Inhba global knockout mouse, which lacks activin A production in all cells (including the gonocytes), and a steroidogenic factor 1 (Sf1)-specific conditional knockout model in which activin A expression in testicular somatic cells is disrupted but gonocyte expression of activin A remains intact. Surprisingly, testis development was comparable in these two models of activin A insufficiency, with similar reductions in Sertoli cell proliferation and minor differences in testis histology. Thus, our findings suggest activin A from male gonocytes is insufficient to promote Sertoli cell proliferation and testis cord expansion in the absence of somatic cell-derived activin A. Evaluation of adult male mice with fetal disruption of activin A revealed reduced testis size, lowered sperm production, altered testicular histology, and elevated plasma FSH levels, defects reminiscent of human cases of androgen-sufficient idiopathic oligozoospermia.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL 61802, USA.
authors.forename: Denise R
authors.initials: DR
authors.lastname: Archambeault
authors.forename: Jessica
authors.initials: J
authors.lastname: Tomaszewski
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Childs
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Humphrey Hung-Chang
authors.initials: HH
authors.lastname: Yao
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D005640:Follicle Stimulating Hormone / Q000097:blood; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D012708:Sertoli Cells / Q000378:metabolism*; D013076:Sperm Count; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism
chemical_list: C422405:activin A; D028341:Activins; D005640:Follicle Stimulating Hormone