Evidence for circadian rhythms in human trophoblast cell line that persist in hypoxia

Circadian clock governs daily rhythmicity of a number of physiological processes such as reproductive functions. The existence of circadian clocks in the placenta is not clearly established. In order to investigate whether human placenta may function as circadian oscillator, we utilized HTR-8/SVneo cells derived from human first-trimester trophoblast. In serum-shocked cells we found circadian expressions for the clock genes Per2 and Dec1 as well as for Dbp, a canonical clock-controlled gene. We obtained similar results for Vegf, a circadian output involved in the control of placental vasculogenesis and trophoblast functions. Interestingly, circadian oscillations persisted and even enhanced in cells experimentally rendered hypoxic with CoCl(2). These results could be explained since the hypoxic milieu of the first-trimester placenta is considered the optimal condition for normal placentation. These data collectively support a possible role for the differential rhythmic expression of Vegf, influenced by circadian clock, in the adjustment of placental vascularization and trophoblast functions to the specific requirements of the different gestational ages.