Somatic and reproductive outcomes in mice treated with cyclophosphamide in pre-pubertal age

Figures & data

Figure 1.  Study design. The animals were divided into placebo and test groups. The effect of CTX was assessed as a function of both dose and age of exposure. Animals were euthanized and tissue was harvested and examined.

Table 1. BMI, femur length and weight, uterine and ovarian weight, means and confidence intervals (95% CI) in the control and CTX-exposed groups.

	GROUPS 1	GROUPS 2	p value
BMI (g/cm^2) (A) Euthanasia at age 56 days (B) Euthanasia at age 95 days	23.8 (20.7-26.9), n = 6 25.5 (21.8-29.3), n = 6	25.9 (24.3-27.5), n = 13 24.9 (21.9-27.9), n = 9	ns ns
Femur length (mm) (A) Euthanasia at age 56 days (B) Euthanasia at age 95 days	14.0 (14.0-14.0) 15.8 (15.1-16.5)	13.3 (13.0-13.5) 14.0 (13.6-14.4)	p < 0.01 p < 0.002
Femur weight (mg) (A) Euthanasia at age 56 days (B) Euthanasia at age 95 days	64.5 (60.9-68.1) 66.5 (65.5-67.5)	63.6 (60.4-66.7) 48.0 (42.9-53.1)	ns p < 0.009
Uterine weight (mg) (A) Euthanasia at age 56 days (B) Euthanasia at age 95 days	58.0 (55.3-60.7) 65.4 (62.4-68.4)	52.4 (47.3-57.6) 49.1 (42.4-55.8)	ns p < 0.005
Ovarian weight (mg) (A) Euthanasia at age 56 days (B) Euthanasia at age 95 days	n/a 10.1 (8.2-11.9)	n/a 4.1 (3.4-4.8)	p < 0.001

Table 2. Follicle stimulating hormone (FSH) means and confidence intervals (95% CI) in controls and the three mouse groups identified by the FSH cut-off values.

	GROUP 1 FSH < 15 mIU/mL (95% CI)	GROUP 2-Normal-FSH FSH < 15 mIU/mL (95% CI)	GROUP 2-DOR 15 < FSH < 30 mIU/mL (95% CI)	GROUP 2-POI FSH > 30 mIU/mL (95% CI)
FSH (mIU/mL) (A) Euthanasia at age 56 days (B) Euthanasia at age 95 days	5.8^ab (3.6-7.9), n = 6 7.9^ab (7.0-8.8), n = 6	9.9 (8.1-11.8), n = 5 8.7 (5.5-11.8), n = 3	20.8^c (18.5-23.2), n = 5 17.1^c (17.0-17.2), n = 3	41.0 (33.9-98.3), n = 3 75.7 (53.1-98.3), n = 3

DOR: decreased ovarian reserve; POI: primary ovarian insufficiency

^a: p < 0.05, Group 1 vs. Group 2 DOR; ^b: p < 0.05, Group1 vs. POI; ^c: p < 0.05, DOR vs. POI

Table 3. Femur length and weight, uterine and ovarian weight, means and confidence intervals (95% CI) in the three groups identified by the FSH cut-off values.

	GROUP 2-NI-FSH FSH<I5 IU/mL (95% Cl)	GROUP 2-DOR 15<FSH<30 IU/mL (95% Cl)	GROUP 2-POl FSH>30 IU/mL (95% Cl)	□ G1 (controls) ▪ G2 (FSH <15) A	□ G2 DOR □ G2 POI B
Femur length (nun)
(A) Euthanasia at age 56 days	13.7 (13.4-13.9), n=5	13.0(12.8-13.2). n=5	13.3(13.0-13.7). n=3
(B) Euthanasia at age 95 days	115(115-11.5), n=3	14.3 (14.0-14.7), n=3	14.3(14.0-14.7). n=3
Femur weight (mg)
(A) Euthanasia at age 56 days	67.0(61.5-72.5)	63.8 (60.5-67.0)	61.0(59.5-62.5)
(B) Euthanasia at age 95 days	50.7 (43.7-57.7)	48(41.5-54.5)	45.3 (43.0-47.6)
Uterine weight (mg)
(A) Euthanasia at age 56 days	58.0 (53.2-62.8)	51.8 (45.5-58.1)	48.5(48.1-48.9)
(B) Euthanasia at age 95 days	65.5 (62.3-68.7)	40.3 (39.3-41.3)	49.3 (48.6-50.1)
Ovarian weight (mg)
(A) Euthanasia at age 56 days	n/a	n/a	life
(B) Euthanasia at age 95 days	4.1 (3.0-5.2)	4.4 (4.0-4.9)	3.5 (3.0-4.0)

^a: p < 0.05, Group 1 vs. Group 2 FSH < 15 IU/mL;

^b: p < 0.05, Group 1 vs. Group 2 DOR;

^c : p < 0.05, Group1 vs. Group 2 POI;

^d: p < 0.05, DOR vs. POI