EFFECTS OF MATERNAL TREATMENT WITH DEXAMETHASONE ON MALE REPRODUCTIVE FUNCTIONS IN THE F1 AND F2 OFFSPRINGS OF WISTAR RATS

Abstract

Maternal treatment with dexamethasone in threatening preterm delivery leads to high basal corticosterone level. This level may interfere with hormones of hypothalamic-pituitary-gonadal axis in the offspring. However, there is paucity of information on the effects of maternal dexamethasone administration on reproductive functions of offsprings. This study was designed to investigate the effects of maternal treatment with dexamethasone on male reproductive functions in the F1 and F2 offsprings. Forty-five pregnant Wistar rats (180-200 g) were divided into 9 groups (n=5). Groups 1 and 6 were administered 0.02 mL/100g/day normal saline (control) throughout pregnancy and lactation respectively. Groups 2, 3, 4 and 5 were administered 100 μg/kg/day dexamethasone at different gestational days 1-7, 8- 14, 15-21 and 1-21 respectively. Groups 7, 8 and 9 were administered 100 μg/kg/day dexamethasone at lactation days 1-7, 1-14 and 1-21 respectively. All the treatments were administered subcutaneously. The F2 offsprings were generated by cross-breeding each of the F1 treatment groups with their control females. The male offsprings (F1 and F2) were sacrificed at 12 weeks of age. Serum Gonadotropin Releasing Hormone (GnRH), Follicle Stimulating Hormone (FSH), Luetinizing Hormone (LH), testosterone and corticosterone were measured using enzyme linked immunosorbent assay. Testicular Superoxide Dismutase (SOD) activity was estimated using spectrophotometry while sperm counts, motility and morphology were assessed by light microscopy. Data were analysed using ANOVA and Tukey’s post hoc test at p=0.05. Serum corticosterone, testosterone, FSH, LH and GnRH in control offsprings were 5.2±1.2 ng/mL, 10.0±1.1 nmoL/L, 5.9±0.4 mLU/mL, 5.7±0.4 mLU/mL, and 3.0±0.2 pg/mL respectively in F1 and 14.9±2.1 ng/mL, 4.9±0.3 nmoL/L, 9.0±1.4 mLU/mL, 5.9±0.9 and 7.0±0.3 pg/mL respectively in F2. Dexamethasone exposure during prenatal days 15-21 and 1-21 significantly raised serum corticosterone (33.7±4.2, 38.6±4.0 ng/mL), GnRH (10.2±2.1, 10.9±1.9 pg/mL), and FSH (6.5±0.2, 7.9±0.3 mLU/mL) respectively but reduced serum testosterone (4.1±1.1, 4.3±1.0 nmoL/L) and LH (3.9±0.1, 3.5±0.1 mLU/mL) respectively when compared with F1 control. However, in the F2 offsprings, dexamethasone reduced serum corticosterone (3.5±0.9, 5.9±0.8 ng/mL), testosterone (2.3±0.2, 2.2±0.4 nmoL/L), FSH (3.9±0.5, 2.4±0.5 mLU/mL) and GnRH (1.2±0.1, 1.5±0.2 pg/mL) respectively when compared with the F2 control. Treatment with dexamethasone at lactation days 1-7, 1-14 and 1-21 also significantly raised the serum corticosterone (15.6±2.1, 18.8±1.9, 19.3±2.1 ng/mL) but reduced serum testosterone (4.5±1.3, 3.4±1.1, 2.5±0.2 nmoL/L), FSH (4.9±0.1, 3.3±0.2, 2.3±0.0 mLU/mL) and LH (2.2±0.1, 1.3±0.1, 0.8±0.1 mLU/mL) respectively when compared with the F1 control. There was a significant reduction in SOD level in dexamethasone-treated groups at prenatal days 1-7, 8-14, 15-21 and 1-21 (13.0±2.0, 10.9±1.0, 8.0±1.4, 4.8±2.3 U/mg/mL respectively) as well as in lactation days 1-7, 1-14 and 1-21 (18.3±1.0, 10.5±0.7, 2.4±0.0 U/mg/mL respectively) when compared with the F1 control (30.7±4.2 U/mg/mL). Dexamethasone treatment at prenatal days 15-21 and 1-21 significantly reduced sperm motility in the F1 and F2 offsprings, but increased the value of abnormal sperm in the F1 and F2 offsprings when compared with respective control groups. Maternal dexamethasone treatment in rats during late gestation and through lactation may disrupt reproductive functions by altering the activity at hypothalamic-pituitary-gonadal axis. These effects may be transferred to the F2 offsprings.