Analysis of the testicular phenotype of the follicle-stimulating hormone beta-subunit knockout and the activin type II receptor knockout mice by stereological analysis.
This study evaluated the role of FSH and activin A on testicular function using quantitative stereological analysis of testicular cell types in mice with targeted disruption of genes encoding the FSH beta-subunit and the activin type IIA receptor (ActRIIA). Using the optical dissector technique, the numbers of Sertoli cells and germ cells per testis were determined. Testis weights in homozygous males lacking the FSHbeta gene or the ActRIIA gene were decreased approximately 60% compared with wild-type or respective heterozygotes. Sertoli cell numbers decreased in both homozygous mice by 30-39%, and there was a comparable decline in germ cell numbers in both models. The degree of germ cell attrition increased in the later stages of spermatogenesis from a 46% reduction of spermatogonia to a 60% decrease in round spermatids. As the FSH levels are decreased in both models, the cellular lesion in both is most likely due to the FSH deficiency. Although the decrease in the Sertoli cell complement represents one cause of lower germ cell numbers, the ability of Sertoli cells to nurture germ cells is compromised by the lower FSH levels, as shown by a decrease in the round spermatid to Sertoli cell ratios in both homozygous models. We conclude that the defects in FSH beta-subunit gene knockout and ActRIIA knockout mice are related to diminished FSH action on both Sertoli cell proliferation and the capacity of Sertoli cells to nurture germ cells.
Wreford
N G
NG
Department of Anatomy and Cell Biology, Monash University, Melbourne, Australia.
Rajendra Kumar
T
T
Matzuk
M M
MM
de Kretser
D M
DM
D030301:Activin Receptors, Type II; D000818:Animals; D002452:Cell Count; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000502:physiology*; D037201:Follicle Stimulating Hormone, beta Subunit; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010641:Phenotype; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology*; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology; D013076:Sperm Count; D013094:Spermatozoa / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000502:physiology*
D037201:Follicle Stimulating Hormone, beta Subunit; D017978:Receptors, Growth Factor; D005640:Follicle Stimulating Hormone; D030301:Activin Receptors, Type II