Perinatal stress effects on later anxiety and hormone secretion in male mandarin voles

The estradiol (E2), estrogen receptor-α (ERα), testosterone (T), and androgen receptor (AR) can contribute to anxiety, but whether they are associated with the reversion of prenatal adverse outcomes remains unclear. Here, we tested the interactive effects of prenatal maternal restraint stress and early postnatal short-term maternal separation on adult male mandarin vole (Microtus mandarinus) behavior and changes in E2, T, and their receptors. The results showed that PS adult males (PS/NH) exhibited an increase in anxiety-like behavior in open-field and elevated plus-maze tests than the other 3 groups, including adult male offspring controls (PC/NH), adult male offspring controls with short-term maternal separation (PC/H), and PS adult males with short-term maternal separation (PS/H). The increase in anxiety-like behavior was associated with significantly lower E2 and T serum levels, had significantly more ERα immunoreactive neurons (ERα-IRs) in some brain regions, as well as significantly fewer AR immunoreactive neurons (AR-IRs) in some brain regions than the other 3 groups. We found it interesting that the PC/H and PS/H were similar to the PC/NH in that they did not produce anxiety-like behavior. However, early postnatal short-term maternal separation reversed prenatally induced changes in E2 and T serum levels and altered ERα-IRs and AR-IRs in the brain. These data suggest that changes in anxious adults may be governed by early environmental factors and their interactions because changes in E2 and T serum levels and the distribution of ERα and AR in the brain result in behavioral changes related to less anxiety into adulthood.