[Establishment and evaluation of a rat model of late-on-set hypogonadism using D-galactose]

To explore the feasibility and duration of establishing a model of late-on-set hypogonadism (LOH) in rats using D-galactose (D-gal) and the optimal concentration of D-gal in modeling.

Thirty-five 8-week-old male SD rats were randomly divided into seven groups of an equal number to receive intraperitoneal injection of normal saline (normal control) or D-gal at 480 mg/kg/d (high-dose), 240 mg/kg/d (medium-dose) and 120 mg/kg/d (low-dose) for 6 or 8 weeks respectively. Another five 18-month-old SD rats were taken as positive controls. After modeling, the animals were subjected to tail suspension test and mating test, weighed, and then sacrificed for examination of the levels of fasting blood glucose (FBG) and serum testosterone (T), testis index and semen parameters, determination of the expressions of the BMAL1 and NR1D1 proteins in the testis tissue by Western blot, and observation of the pathological and ultrastructural changes in the testis tissue under the light microscope and transmission electron microscope.

Compared with the normal controls, the serum T level was significantly decreased in the 6-week medium-dose D-gal (6WMD), 6-week high-dose D-gal (6WHD), 8WMD, 8WHD and positive control groups (P < 0.05), and so were sperm concentration and the percentage of progressively motile sperm (PMS) in the 8WHD and positive control groups (P < 0.05), and the numbers of captures and ejaculations in all the model rats and positive controls (P < 0.05), while the body weight was markedly increased in the 8-week low-dose D-gal (8WLD), 8WMD and 8WHD groups (P < 0.05), and so were the tail suspension time in the 6WHD, 8WHD, 8WMD, 8WLD and positive control groups (P < 0.05) and the FBG level in all the model rats and positive controls (P < 0.05). The expression of the BMAL1 protein was significantly decreased in the 6WHD, 8WLD, 8WMD, 8WHD and positive control groups (P < 0.05), and so was that of NR1D1 in the 8WMD, 8WHD and positive control groups (P < 0.05). Compared with the positive controls, no statistically significant differences were observed in the serum T level in the 6WHD and 8WHD groups (P > 0.05), the testis index in the 8WMD and 8WHD groups (P > 0.05), sperm concentration, percentage of FMS, time of tail suspension and numbers of captures and ejaculations in the 8WHD group (P > 0.05), the level of FBG in the 6WMD, 6WHD, 8WLD, 8WMD and 8WHD groups (P > 0.05), the expression of BMAL1 in the 6WHD, 8WLD, 8WMD and 8WHD groups (P > 0.05), and that of NR1D1 in the 6WLD, 8WMD and 8WHD groups (P > 0.05). Pathological and ultrastructural changes in the testis tissue were observed in all the model rats and positive controls, most significantly in the 8WHD and positive control groups.

It is feasible to establish an LOH model in male SD rats by intraperitoneal injection of D-gal, most recommendably at the centration of 480 mg/kg/d for 8 weeks.