Numerous cohort studies on the “Dutch famine,” in which pregnant women were exposed to a severe food shortage, have indicated a linkage between famine exposure during early pregnancy and a heightened risk of schizophrenia (SCZ) onset among offspring. These findings endorsed the Developmental Origins of Health and Disease (DOHaD) theory. However, the underlying mechanisms remain unclear. In this study, we exposed fertilized mice to a 16-hour overnight fast on embryonic day 1 (E1), E3, and E5, to mimic early pregnancy famine exposure. Offspring were examined for phenotypes in adulthood. Using 10-week-old offspring or older, we investigated the dendritic spine density of pyramidal neurons in the medial prefrontal cortex (mPFC) (5-8 offspring/group) and SCZ-related behavioral phenotypes (prepulse inhibition test, open field test, elevated plus maze test, forced swim test, and tube test) (10-12 offspring/group). Furthermore, immunofluorescent analysis was conducted to evaluate the neuronal and glial morphologies in the mPFC using specific markers (6-7 offspring/group). Male offspring of fasted dams exhibited significantly decreased spine density and SCZ-related behavioral deficits, including impaired sensory-motor gating, increased anxiety level, enhanced active coping strategy to acute stress, and escalated social dominance. These phenotypes resemble schizophrenia and are accompanied by increased microglial density and hyper-ramified microglia in the mPFC. Overall, maternal fast exposure during early pregnancy can induce SCZ-related phenotypes in male offspring, associated with microglia proliferation and hyper-ramification, providing a new animal model to understand the pathophysiology of SCZ from the DOHaD perspective.