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Hemozoin (HZ) is a waste product of hemoglobin digestion by Plasmodium and has been implicated in several pathological processes, including inflammation, oxidative stress, endothelial dysfunction, and immune dysregulation. Studying the effects of HZ on the human placenta is essential to understanding the impact of malaria infection during pregnancy. The present study explored the impact of HZ produced by Plasmodium and β-hematin, referred to here as natural HZ (nHZ) and synthetic HZ (sHZ), respectively, on human placental explants exposed in vitro ., Methodology: nHZ was derived from Plasmodium falciparum cultures and isolated using magnetic MACS® Separation Columns (Miltenyi Biotec, Auburn, CA) [1]. sHZ was synthesized from hemin closure in an aqueous solution. Both nHZ and sHZ were characterized by infrared spectroscopy and scanning electron microscopy. Human placental explants (HPE) were exposed to 5 and 10 μg/mL of nHZ and sHZ for 24 h, and tissue integrity was studied using histological and immunohistochemical techniques., Results: The studies have demonstrated that the exposition of both the nHZ and sHZ to placental tissue are comparable and cause effects in increased STB detachment, dysregulation of collagen distribution in the villous stroma, and increase in the frequency of cell apoptosis. This contributes to the understanding of the pathophysiology of malaria in pregnancy using synthetic products such as β-hematin., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)