Absence of RAD21L and REC8 arrest mouse spermatogenesis in early prophase I. (A) dKO-kls mice show a 70% reduction in testes size compared with wild type. Similar reductions are observed in Rad21l^−/− and Rec8^−/− males. (B) Mutation of both Rad21l and Rec8 elicits an arrest of spermatogenesis at stage IV characterized by intermediate spermatogonia (arrows) in a representative section of a seminiferous tubule. Massive apoptosis of spermatocytes (condensed nuclei indicated by asterisks) and absence of mature spermatozoa/spermatids are observed in the dKO-kls tubules. A similar arrest is observed in seminiferous tubules from singly mutant Rad21l and Rec8 mice. (C) Immunolabeling for SYCP3 in spermatocytes from a wild-type mouse at early and late leptonema and spermatocytes arrested at a leptotene-like stage from a dKO-kls mouse. (D) dKO-kls spermatocytes arrested at the leptotene-like stage show absence of chromosomal synapsis. Double immunolabeling for SYCP3 and SYCP2 or SYCP1 shows SYCP3/SYCP2 aggregates without synapsis as indicated by the lack of SYCP1 labeling in double mutant spermatocytes. Spermatocytes from Rad21l^−/− (zygotene-like arrest), Rec8^−/− (zygotene-like arrest), and wild-type (zygotene stage) mice show AEs and synapsed LEs with stretches of SYCP1. Bars: (A) 5 mm; (B) 25 µm; (C and D) 100 µm.