Intrauterine hyponutrition reduces fetal testosterone production and postnatal sperm count in the C57BL/6N

There has been growing interest in the relationship between maternal undernutrition and reproductive disorders in male offspring. In the present study, we determined the effects of maternal calorie restriction throughout the critical period for in utero development of the male reproductive system, termed the “masculinization programming window” on the reproductive system of mice. The intratesticular testosterone concentration of the fetuses of calorie-restricted (R) dams was lower than in control fetuses at 17.5 days post coitum. In addition, there was global down-regulation of genes encoding steroidogenic enzymes and a low sperm count in the offspring of R dams (R-offspring) at 6 weeks of age. Microarray analysis of the testes of the offspring identified dysregulation of several genes that might explain the derangement in spermatogenesis in the R-offspring. Thus, the present study provides insights into the impact of maternal undernutrition on the male reproductive system in mice. The deleterious effects probably originate in lower androgen exposure during the “masculinization programming window.” We used two groups of female mice with vaginal plugs. One group of mice were fed a powdered regular chow diet ad libitum throughout the pregnant course (control females) (C-females), and the other group of mice were fed 50% of the mean daily intake of the C-females from 6.5 days post coitum (dpc) (calorie-restricted females) (R-females). Pregnant C- and R-females gave birth to control offspring (C-offspring) and calorie-restricted offspring (R-offspring), respectively. After determining genetic sex, male mice only were utilized for the subsequent examinations. Male C-offspring were raised by their mothers, whereas male R-offspring were cross-fostered and raised by unrelated C-females. After weaning, male C- and R-offspring were fed a regular chow diet ad libitum. At 6 weeks (42 days) of age, they were sacrificed. Testes were immediately removed for subsequent studies including microarray analysis. RNA samples obtained from the testes of C- and R-offspring were utilized for microarray analysis using single-color SurePrint G3 mouse GE 8×60K v2 Microarrays. We extracted genes satisfying the combined criterion for true positive expression differences of a fold difference of > 1.5 or < 0.66 and a false discovery rate (q value) of < 0.05. n = 5 for C or R offspring.