Qualitative and quantitative decline in spermatogenesis of the follicle-stimulating hormone receptor knockout (FORKO) mouse

Sertoli cells express functional receptors for FSH, one of the two pituitar y hormones that regulate spermatogenesis in mammals. We recently produced g enetic mutant (FORKO) mice that lack FSH receptor, in order to examine the effects on testicular function and fertility. Mutant males exhibited weight loss of testis, epididymis, and seminal vesicle as well as low levels of t estosterone. Except for reduced seminiferous tubular diameter, no gross cha nges were apparent upon histological examination. Analysis of testicular ge rm cells by flow cytometry revealed a significant increase in the percentag e of 2C cells (spermatogonia and non-germ cells) and a significant decrease in the percentage of HC cells (elongated spermatids) of FORKO males. The a bsolute number of homogenization-resistant elongated spermatids was also si gnificantly reduced in the mutant males. A P-fold increase in c-kif-positiv e 2C cells was recorded in the mutant mates. Elongated spermatids of FORKO males showed a dramatic increase in propidium iodide binding suggesting red uced nuclear compaction. The increase in size of the sperm head in mutants, as well as susceptibility to dithiothreitol-induced decondensation, sugges ts the inadequate condensation of sperm chromatin. Sperm chromatin structur e assay, a technique that reflects DNA stability, revealed that sperm from FORKO males are susceptible to acid denaturation, indicating the poor quali ty of sperm. These data allow us to conclude that genetic disruption of FSH receptor signaling in the rodent induces major changes that might contribu te to reduced fertility.