Figure 6. The action of NO during the critical infantile period is required for establishing a sexually mature phenotype.

(a) Age at vaginal opening or (c) puberty and (d) adult estrous cyclicity in Nos1^+/+, Nos1^+/- and Nos1^-/- female mice untreated (a: n=7,11,6; c: n=5,6,8; d: n=5,6,6) or treated with iNO (grey-shaded area, a: n=6,7,6; c: n=6,7,6; d: n=7,8,5) or Sildenafil (blue-shaded area, a: n=4,7,7; c: n=4,7,7; d: n=4,5,7) during the infantile period. Nos1^+/+ values are compared to those of Nos1^+/- and Nos1^-/- mice for each group of measurements [one-way ANOVA with Dunnett’s post-hoc test for a (untreated) or Kruskal-Wallis with Dunn’s post-hoc test were used as detailed in Table S2]. Red asterisks: comparison between mice of the same genotype but subjected to different treatments (a: one-way ANOVA with Dunnett’s post-hoc test, b,d: Kruskal-Wallis with Dunn’s post-hoc test). (b) Age at balanopreputial separation in Nos1^+/+, Nos1^+/- and Nos1^-/- male mice untreated (n=4,9,3) or treated with Sildenafil (blue-shaded area, n=3,13,5). Nos1^+/+ values are compared to those of Nos1^+/- and Nos1^-/- mice for each group of measurements (Kruskal-Wallis test with Dunn’s post-hoc test). Red asterisks: comparison between mice of the same genotype but subjected to different treatments (unpaired t-test).

(e-h) Age at vaginal opening (e) and puberty (f) (unpaired t-test; n=10,9), and adult estrous cyclicity (g) (Mann-Whitney U test; n=8,7) after daily injections of vehicle or L-NAME during the infantile period.

(h) LH levels in diestrus and proestrus female mice subjected or not to LNAME treatment during the infantile period (Mann-Whitney U test; n=5,5). ** P = 0.008.

Values indicate means ± SEM. N>3 independent litters. *P<0.05; **P<0.01; *** P<0.001.