Delay in sexual maturity of the follicle-stimulating hormone receptor knockout male mouse.
In the highly organized and complex process of mammalian spermatogenesis, the development of an undifferentiated diploid germ cell into a fully differentiated and mature spermatozoon is orchestrated in a time frame unique for each species including man. If the various hormonal signals including environmental cues that play a critical part in initiating these events are not properly executed, various deficiencies including delay in sexual maturity or puberty are likely. In this study we have followed testicular development and spermatogenesis in the FSH receptor knockout (FORKO) mice from Day 7 onward by using histology and quantitative DNA flow cytometry. The drastic reduction in testicular weight and shrinkage of seminiferous tubules that occurred at this early age persisted into the adult stage in the FORKOs, suggesting inhibition of the initial developmental processes. The round spermatids that were clearly abundant on Day 21 in the wild-type and heterozygous males were few and present only in some tubules of the FORKOs. There were no elongated spermatids in FORKO males on Day 35. The sperm produced by Day 49 FORKOs were already aberrant, a feature that persisted into adulthood in these animals. As all these changes occurred in a background of normal circulating testosterone levels, we may conclude that the delay in testicular development is a consequence of the loss of FSH-receptor signaling. The delay in sexual maturity of FORKOs was accompanied by reduction in fertility as evidenced by mating studies. Based on these data we suggest that the FORKO mouse might be a useful experimental model to define the molecular mechanisms that underlie the delay in puberty.
Krishnamurthy
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The Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7.
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Morales
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Sairam
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D000818:Animals; D001835:Body Weight; D002452:Cell Count; D004247:DNA / Q000032:analysis; D004822:Epididymis / Q000033:anatomy & histology / Q000254:growth & development; D005434:Flow Cytometry; D015870:Gene Expression; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D011962:Receptors, FSH / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012671:Seminiferous Tubules / Q000033:anatomy & histology; D012708:Sertoli Cells; D012741:Sexual Maturation; D013076:Sperm Count; D013087:Spermatids / Q000166:cytology; D013091:Spermatogenesis; D019089:Stem Cell Factor / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000254:growth & development; D013739:Testosterone / Q000097:blood
D011962:Receptors, FSH; D019089:Stem Cell Factor; D013739:Testosterone; D004247:DNA