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Second, concurrent perfusions of mice from many other knockout models studied in our laboratory by identical procedures never resulted in dilated spaces of the type seen in the FORKO mice, indicating that these spaces are not related to the fixative or the method used to perfuse FORKO mice. Third, dilated cytoplasmic areas in different generations of germ cells were never observed in the FOR-KO mice. The dilations were exclusively restricted to cytoplasm of Sertoli cells, suggestive of something specific about the relationship of the knockout to these particular cells. Fourth, in all cases, there were no signs of bloating of the mitochondria, Golgi apparatus, or lysosomes of germ cells or Sertoli cells, perturbations that are commonly seen in poorly fixed immersed testes. Thus, the dilations of the Sertoli cell cytoplasm appear to be a direct consequence of the absence of FSH-R signaling in these cells. The fact that these spaces appear to be filled with fluid, as indicated by the absence of the finely flocculent ground substance seen in wild-type mice (Fig. 11), suggests that FSH-R signaling could potentially regulate water balance in the Sertoli cell.