Effects of the adjudin-FSH mutant conjugate on the testis, kidney, liver, and small intestine. Adjudin-FSH mutant conjugate (50 µg containing ~0.5 µg of adjudin/kg b.wt.) was administered to adult rats (~300 g b.wt., n = 8 per time point) intraperitoneally via a 28-gauge needle. Rats were sacrificed at 2, 4, 6, and 12 weeks thereafter for histological analysis by hematoxylin & eosin staining. A, cross-section of the testis from normal rats (control) without treatment. B, by 2 weeks after treatment, almost all elongating/elongated spermatids were depleted from the seminiferous epithelium. C, by 4 weeks, ~98% of the tubules examined were devoid of spermatids and spermatocytes, and the tubule diameter was reduced by ~35%. D, magnified view of the boxed area in C, showing a tubule that contained only Sertoli cells, spermatogonia, and a few spermatocytes. E, by 6 weeks, germ cells began to repopulate the seminiferous epithelium. F, by 12 weeks, ~90% of tubules were indistinguishable from those of the control testes. G to I, cross-sections of kidney (G), liver (H), and small intestine (I) 4 weeks after treatment. No histological changes were detected in these organs at this time or at 6 or 12 weeks after treatment versus control rats. In addition, no histological changes were detected in skeletal muscle versus control rats at 4, 6, or 12 weeks after treatment (data not shown). Bars in A to C and E to I, 150 µm; D, 40 µm. J, changes in testes weights (organ pair) after treatment. K, summary of the fertility test (n = 4 rats) results. The fertility efficacy of control rats was arbitrarily set at 100%. [Reproduced from A male contraceptive targeting germ cell adhesion. Nat Med 12:1323–1328. Copyright © 2006 Nature Publishing Group. Used with permission.]