<p>Hypoxia during pregnancy leads to impaired development of the fetal nervous system and is one of the main causes of infant mortality. Disruption of intracellular signaling processes under hypoxia is one of the leading mechanisms of neurotoxic effects on the developing fetus; however, there are no studies identifying which specific signaling pathways are critical for the development of neurodamage caused by hypoxia induced by methionine overload. In this study, the levels of signaling molecules and transcription factors responsible for proliferation, apoptosis, and hypoxic-ischemic adaptation—namely HIF1α, VEGFβ, TGFβ, STAT3, p53, JNK1, JNK2, p38 MAPK, and ERK1/2—were analyzed in the whole brains of rat fetuses at two developmental stages, the 14th and 20th days of pregnancy, occurring under experimental methionine-induced hypoxia. On day 14 of pregnancy, the levels of all examined markers in the fetal brain, including the hypoxia marker HIF1α, did not change in the methionine-loaded group compared to controls, except for JNK2, whose content sharply decreased. By day 20 of pregnancy, the fetal brains of the experimental group showed selective activation of the “stress ensemble” TGFβ/JNK2/HIF1α/VEGF, without changes in the activation levels or total content of the signaling molecules STAT3, p53, ERK1/2, and p38 MAPK. This two-phase response reflects the development of a neurotoxic environment in the fetal brain, formed by both oxidative and hypoxic stress at different developmental stages. JNK2 protein kinase may act as a modulator switching between adaptive and pathological stress responses. The TGFβ/JNK2/HIF1α/VEGF signaling pathway mediates the pathological effects of hypoxic stress and potentially represents an important target for therapy of neurodamage in the fetus and newborn.</p>