Prenatal caﬀeine and glucocorticoid−IGF1 axis-mediated testicular dysplasia
The negative effects of prenatal caffeine exposure (PCE) in relation to testicular development via intrauterine growth retardation are well known. However, the underlying mechanism was not understood.
Pei et al. investigated the effects of low and high dose (30 and 120 mg/kg per day) exposure to caffeine in pregnant rats (intragastric administration from gestational day 9 to 20). In vivo findings showed that high dose PCE resulted in testicular dysplasia and dysfunction in male fetuses, with increased serum corticosterone and decreased insulin-like growth factor 1 (Igf1) expression and histone-3 lysine-14 acetylation (H3K14ac) at its promoter region. After birth, the serum corticosterone concentration gradually decreased in the PCE (120 mg/ kg per day) offspring, whereas the expression and H3K14ac level of Igf1 gradually increased, with obvious catch-up growth and testicular development compensation. In vitro studies suggested that the effects of caffeine on Igf1 expression were indirect and caused via elevated corticosteroid exposure rather than caffeine.
Understanding an underlying mechanism of PCE-induced testicular dysfunction via the glucocorticoid−IGF1 axis may help prevent and treat testicular development abnormalities in the future.
Read the full article in Journal of Endocrinology 242 M17−M32