Effects of prenatal exposure to genistein on learning and memory function in Sprague Dawley rat offspring

Abstract

Learning and memory, primarily governed by the hippocampus, involves acquiring, retaining, and recalling information. The hippocampus creates and modulates memories, regulates hypothalamic functions, and influences emotions. Key plasticity processes, long-term potentiation (LTP) and long-term depression (LTD), respectively strengthen and weaken synaptic connections to support memory. However, genetic, environmental, and dietary factors can disrupt these functions. Phytoestrogens, natural oestrogen receptor activators found in foods like soy, may act as endocrine disruptors. Genistein, a common phytoestrogen structurally similar to estradiol, binds to oestrogen receptors in the hippocampus, potentially altering memory processes. Infants are particularly vulnerable, as genistein can cross the placenta and blood-brain barrier. Although genistein is generally beneficial, its prenatal effects on learning and memory are not fully understood, with some effects only observable in adulthood. This study examines genistein’s prenatal impact on learning and memory in rat offspring, assessing behaviour, hippocampal synaptic structure, and protein levels related to memory processes. Pregnant female Sprague Dawley rats were treated with either the vehicle, cottonseed oil (Control group) or Genistein at 5 mg/kg (G5 group) or 10 mg/kg (G10 group) by oral gavage from gestational day (GND) 7 to GND 21; thereafter, both dams, and later offspring postweaning received the vehicle until postnatal day (PND) 84. Thereafter, two behavioural experiments, the Morris water maze (MWM), and the novel object recognition (NOR) were performed to assess spatial learning and memory, and recognition memory respectively. Following euthanasia, the hippocampus was collected and assessed for synaptic ultrastructural changes by transmission electron microscopy as well as quantification of synaptophysin and cAMP response element-binding (CREB) proteins by western blotting. Behavioural assessments indicate that genistein showed no effect on spatial memory among male and female offspring, but male offspring receiving a lower dose showed a reduced learning ability compared to controls. Administration of genistein did not have an effect on recognition memory in both male and female offspring. Analysis of hippocampal synapses showed that genistein had minimal impact on hippocampal synaptic structures, except for a reduced active zone length in females at lower doses, suggesting decreased signal transmission efficiency. Additionally, MIS formation pointed to disruptions in LTP mechanisms, while both synaptophysin and CREB expression remained unaffected. This suggests that while lower doses of genistein showed some effectiveness, its impact on memory remains unclear due to minimal effects at the ultrastructural level.