Maternal protein undernutrition during lactation reduces body weight gain and adiposity and delays pubertal onset in male Wistar offspring.

BACKGROUND

Maternal protein restriction during lactation affects the metabolic and reproductive development of offspring by modulating the hypothalamic-pituitary-testicular (HPT) axis.

OBJECTIVE

The regulation of the HPT axis during peripuberty remains poorly understood, as does the impact of maternal protein restriction on this process. In this study, we investigated the impact of maternal protein restriction during lactation on the function of the HPT axis in male Wistar rats from peripuberty to young adulthood.

METHODS

From postnatal day (PND) 0 (birth) to PND21 (weaning), the dams were fed either a normal-protein diet (NP; 20.5% protein) or a low-protein diet (LP; 4% protein). Male offspring were evaluated at PND 35, 45, and 55 (peripubertal stages) and PND 90 (young adulthood). Assessments included body weight (BW), adiposity, pubertal timing, serum testosterone concentration and hypothalamic and testicular gene expression (RT‒qPCR).

RESULTS

Compared with NP offspring, LP offspring exhibited delayed pubertal onset and reduced BW during puberty. At PND 35, LP offspring showed improved glucose tolerance, reduced testicular weight, and lower expression of sex steroid receptors (Esr1, Esr2, Gper1, and Ar) in the hypothalamus. In the testes, LP offspring expressed lower levels of estrogen receptor alpha (Esr1), luteinizing hormone receptor (Lhcgr), a Sertoli cell marker (Lgals1), and the spermatogenic genes spermatocity (Rhcg) and spermatids (Lrrc34). In contrast, they had higher aromatase expression (Cyp19a1) and higher estrogen receptor beta expression than their age-matched NP offspring did. At PND 45, hypothalamic Kiss1 expression was higher, whereas LP offspring presented lower testicular expression of genes involved in steroidogenesis and spermatogenesis, including Ar, Gper1, Cyp19a1, and Rhcg, accompanied by decreased serum testosterone levels. By PND 55, the expression of hypothalamic tachykinin precursor 3 (Tac3) was increased, whereas that of estrogen receptor genes (Esr1, Esr2, and Gper1) and the androgen receptor (Ar) was decreased. In the testes, Lgals1 expression was increased, whereas the expression of the spermatogenesis-related genes Fshr and Kit was reduced compared with that in the NP offspring. In young adulthood, body weight, adiposity, and serum sex hormone levels remained lower in the LP group, and no significant changes in hypothalamic or testicular gene expression were detected.

CONCLUSION

In summary, severe maternal protein restriction during lactation delays the onset of male puberty and induces age-dependent alterations in hypothalamic and testicular gene expression, leading to dysregulation of the HPT axis during the peripubertal period.