The effects of prenatal genistein exposure on anxiety-like and depressive-like behaviour in Sprague Dawley rat offspring

Abstract

Genistein is a natural endocrine-disrupting chemical (EDC), found in soy-based foods. It can interact with oestrogen receptors (ERs) and mimic and/or can disrupt the functioning of endogenous oestrogen. Genistein has been shown to have population and context-dependent positive or negative physiological effects on the nervous system. The effects of soy on behaviour has been limited to investigation of high or low intake in Asian or Western populations, respectively, with limited understanding on behavioural effects in populations which consume average amounts of soy. Prenatal stress impacts foetal development and is often linked to permanent impairments in adulthood. An overactive stress response due to long-term stress exposure leads to behavioural abnormalities, including the development of depression and anxiety. Oestrogen plays an integral role in differential manifestation of male and female stress responses and behaviour, and disruptions to this system could lead to severe psychological outcomes. Therefore, this study aimed to identify the effects of prenatal exposure to a natural oestrogenic EDC, genistein, on anxiety-like and depressive-like behaviours in male and female Sprague Dawley rat offspring. This was achieved using the behavioural paradigms, the sucrose preference test (SPT) and the elevated plus maze (EPM), which investigate rodent depressive-like and anxiety-like behaviours, respectively. This study also included biochemical testing for the stress response marker corticosterone (CORT) and the indirect behavioural marker, brain-derived neurotrophic factor (BDNF) levels and its precursor (proBDNF) in prefrontal cortex (PFC) tissue. Pregnant Sprague Dawley rats were exposed at either genistein at 5 mg/kg (G5) or 10 mg/kg (G10) or vehicle (control; C), during the 14-day prenatal period (GND 7-21). Behavioural tests (SPT and EPM) and biochemical analyses were conducted on female and male offspring in adulthood (PND 86- 89). Results revealed sex-related differences in the baseline parameters observed for control animals with respect to PFC proBDNF and BDNF concentrations and anhedonia behaviours. They also indicated that genistein prevented BDNF formation in males at 5 mg/kg. Additionally, the findings showed that prenatal exposure to genistein, at 10 mg/kg, reduced BDNF levels, only in male offspring, an indirect marker of depression. The results also revealed that 10 mg/kg of prenatal genistein exposure increased exploratory behaviour in male offspring, i.e. reduced anxiety-like behaviour, with prenatal genistein exposure attenuating the sex differences found in the anxiety-like behaviours of male and female offspring. This study has contributed to the established influence of genistein on depression and anxiety by highlighting a sex differential effect of genistein when exposed during the vulnerable prenatal period. With the framework in mind from this study’s findings, a future direction for research includes assessing genistein’s dose of efficacy in inducing advantageous versus disadvantageous effects on male and female depression- and anxiety-related behaviours as well as their indirect markers and further exploring the biochemical/neurobiological mechanisms underlying the observed effects.