Figure 3.
BRDT Inhibition with a Testis-Permeable Small Molecule Reduces Testis Size and Sperm Counts and Motility
(A) Pharmacokinetic analysis of JQ1 in plasma (black lines) and testis (red lines) following a single administration of JQ1 (50 mg/kg IP) to male mice. Data represent the mean ± SD.
(B) Gross analysis of testes from 9-week-old mice that received control or JQ1 (50 mg/kg daily) for 3 weeks.
(C) Testis weights from mice treated with control or JQ1 (50 mg/kg QD) for 3–6 weeks, 6–9 weeks, or 6–12 weeks of age. Data represent the mean ± SEM and are annotated with P values obtained from a two-tailed t test (∗p < 0.05).
(D) Graphical representation of sperm counts obtained from the entire epididymides of males treated with JQ1 or control from 6–9 weeks of age or the tail of the epididymis of males treated from 6–12 weeks of age with vehicle or JQ1 (50 mg/kg QD). Data represent the mean ± SEM (∗p < 0.05).
(E) Motility of mature sperm obtained from the cauda epididymis of adult males treated with JQ1 (50 mg/kg daily) from 6–12 weeks of age. Data represent the mean ± SEM (∗p < 0.0001).
(F) Pharmacokinetic analysis of JQ1 in plasma (black lines) and testis (red lines) following twice-daily (BID) administration of JQ1 (50 mg/kg IP) to male mice. Data represent the mean ± SD.
(G) Testis weights (mg) from mice treated with control or JQ1 (50 mg/kg BID) from 9–12 weeks of age. Data represent the mean ± SEM (∗p < 0.05).
(H) Sperm counts obtained from the cauda epididymis of males treated from 9–12 weeks of age with vehicle or JQ1 (50 mg/kg BID). Data represent the mean ± SEM (∗p < 0.05).
(I) Motility of mature sperm obtained from the cauda epididymis of adult males treated with JQ1 (50 mg/kg BID) or vehicle from 9–12 weeks. Data represent the mean ± SEM (∗p < 0.001).
(J) Cross-sectional area of seminiferous tubules from JQ1-treated mice (50 mg/kg QD for 3–6 weeks or 6–12 weeks, or 50 mg/kg BID for 9–12 weeks, as shown) or control (∗p < 0.05).
(K, L, and M) Male mice treated with JQ1 or vehicle from 6–12 weeks exhibit statistically similar serum levels of (K) testosterone, (L) luteinizing hormone (LH), and (M) follicle-stimulating hormone (FSH).