Acute iron overload leads to hypothalamic-pituitary-gonadal axis abnormalities in female rats

Iron plays a critical role in a mammal's physiological processes. However, iron tissue deposits have been shown to act as endocrine disrupters. Studies that evaluate the effect of acute iron overload on hypothalamic-pituitary-gonadal (HPG) axis health are particularly sparse. This study demonstrates that acute iron overload leads to HPG axis abnormalities, including iron accumulation and impairment in reproductive tract morphology. Female rats were treated with iron-dextran (Fe rats) to assess their HPG morphophysiology. The increasing serum iron levels due to iron-dextran treatment were positively correlated with higher iron accumulation in the HPG axis and uterus of Fe rats than in control rats. An increase in the production of superoxide anions was observed in the pituitary, uterus and ovary of Fe rats. Morphophysiological reproductive tract abnormalities, such as abnormal ovarian follicular development and the reduction of serum estrogen levels, were observed in Fe rats. In addition, a significant negative correlation was obtained between ovary superoxide anion and serum estrogen levels. Together, these data provide in vivo evidence that acute iron overload is toxic for the HPG axis, a finding that may be associated with the subsequent development of the risk of reproductive dysfunction.