Qualitative and Quantitative Decline in Spermatogenesis of the Follicle-Stimulating Hormone Receptor Knockout (FORKO) Mouse1

Abstract

Sertoli cells express functional receptors for FSH, one of the two pituitary hormones that regulate spermatogenesis in mammals. We recently produced genetic 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 testosterone. Except for reduced seminiferous tubular diameter, no gross changes were apparent upon histological examination. Analysis of testicular germ cells by flow cytometry revealed a significant increase in the percentage of 2C cells (spermatogonia and non-germ cells) and a significant decrease in the percentage of HC cells (elongated spermatids) of FORKO males. The absolute number of homogenization-resistant elongated spermatids was also significantly reduced in the mutant males. A 2-fold increase in c-kit-positive 2C cells was recorded in the mutant males. Elongated spermatids of FORKO males showed a dramatic increase in propidium iodide binding suggesting reduced nuclear compaction. The increase in size of the sperm head in mutants, as well as susceptibility to dithiothreitol-induced decondensation, suggests the inadequate condensation of sperm chromatin. Sperm chromatin structure assay, a technique that reflects DNA stability, revealed that sperm from FORKO males are susceptible to acid denaturation, indicating the poor quality of sperm. These data allow us to conclude that genetic disruption of FSH receptor signaling in the rodent induces major changes that might contribute to reduced fertility.

Germ cell abnormalities in streptozotocin induced diabetic mice do not correlate with blood glucose level

“…The cells were washed and stained with propidium Iodide (25 μg/ml, with RNAse-40 μg/ml) and DNA content was analyzed in flow cytometer (BD FACS Calibur, San Jose, USA). The data were analyzed using Cell Quest Pro software [13].…”

Fertility and spermatogenesis are altered in α1b-adrenergic receptor knockout male mice

“…It is thus unlikely that this gonadotropin favorably influences the completion of meiosis and the initiation of spermiogenesis via Sertoli cells in the infertile a1b-AR-KO males. This contrasts with data obtained in other transgenic models (Krishnamurthy et al 2000, Allan et al 2001. Besides the drastic deficit in testosterone production in the a1b-AR infertile male mice, a deleterious effect of high testicular concentrations of inhibin B on spermatogenesis (van Dissel-Emiliani et al 1989) cannot be excluded.…”

La signalisation FSH a-t-elle un sexe ?

“…Chez le mâle Chez la femelle Chaîne β de la FSH Mâles fertiles, taille testiculaire réduite [28] Femelles infertiles, blocage du développement folliculaire au stade pré-antral, anovulation [28] R-FSH Degré variable d'altéra-tion de la fertilité, spermatogenèse désorganisée, rendement spermatique réduit [3,4] Femelles infertiles, blocage du développement folliculaire au stade pré-antral, anovulation [3] A B vivo, dans les cellules de Sertoli, un mutant de CREB non phosphorylable. Il en résulte une spermatogenèse perturbée avec une apoptose des spermatocytes, ce qui suggère que CREB est nécessaire à la production d'un facteur dérivé des cellules de Sertoli utile à la survie des cellules germinales [6].…”

“…Les femelles sont complètement infertiles, elles n'ont pas d'ovulation car le développement de leurs follicules est bloqué à un stade précoce, avant la formation de l'antrum ( Figure 1B). En revanche, les mâles restent fertiles malgré une spermatogenèse désorganisée et une diminution de la sécrétion d'androgènes [3,4]. Ces différences phénotypiques s'expliquent-elles par une fonction biologique distincte de la FSH chez le mâle et chez la femelle ?…”