Figure 7.

BRDT Inhibition with JQ1 Causes a Reversible Contraceptive Effect in Male Mice

(A) Adult males were pretreated for 6 weeks with vehicle control (n = 7) or JQ1 (50 mg/kg QD; n = 3) and then caged continuously with two females each while continuing 50 mpk QD for month 1 and escalating to 75 mpk QD for month 2. JQ1 treatment was stopped at the end of month 2 of mating. Graphical representation of pups born in each month to the females reveals a contraceptive effect evident in months 1–3 (data represent mean ± SEM; ^∗p < 0.001) and durable restoration of fertility at month 4.

(B) Adult males were pretreated for 6 weeks with vehicle (n = 7) or JQ1 (50 mg/kg QD; n = 4) and then caged continuously with two females each while continuing 50 mg/kg QD for month 1, escalating to 75 mg/kg QD for month 2, and further escalating to 50 mg/kg BID for month 3. JQ1 treatment was stopped at the end of month 3 of mating. Graphical representation of pups born in each month to the caged females reveals a complete contraceptive effect evident in months 3–5 (data represent mean ± SEM; ^∗p < 0.001) and durable restoration of fertility at month 6.

(C–E) Graphical representation of (C) testis mass (mg), (D) sperm count, and (E) sperm motility of adult control males (n = 3) and JQ1-treated males (n = 3) following a 4 month recovery from the low-dose regimen shown in (A) (data represent mean ± SEM; NS, not significant).

(F–H) Graphical representation of (F) testis mass, (G) sperm count, and (H) sperm motility of adult control males (n = 4) and JQ1-treated males after 3 weeks of 50 mg/kg BID treatment (n = 2), as well as following 10 days (n = 2), 30 days (n = 2), and 60 days (n = 2) of recovery from the high-dose (B) regimen (data represent mean ± SEM; ^∗p < 0.05).

(I and J) Microscopic analysis of seminiferous tubules from (I) control and (J) JQ1-treated males following 4 months of recovery reveals compete histological recovery.

(K) Litter sizes and pups born following JQ1 cessation are normal.

See also Figure S4.