S. G. Vari¹*, O. Shevchuk², A. Boychuk³, S. Kramar⁴,
Z. Nebesna⁴, Y. Yakymchuk⁵, L. Kobylinska⁶, V. Chernyshenko⁷,
D. Korolova⁷, A. Gaspar-Suranyi⁸, T. Altorjay⁸, R. Gaspar⁹

¹International Research and Innovation in Medicine Program, Cedars-Sinai Medical Center, Los Angeles, California, USA;
²Department of Pharmacology and Clinical Pharmacology, I. Horbachevsky Ternopil National Medical University, Ukraine;
³Department of Obstetrics and Gynecology, I. Horbachevsky Ternopil National Medical University, Ukraine;
⁴Department of Histology and Embryology, I. Horbachevsky Ternopil National Medical University, Ukraine;
⁵Department of Therapeutics and Family Medicine, I. Horbachevsky Ternopil National Medical University, Ukraine;
⁶Department of Biochemistry, Danylo Halytsky Lviv National Medical University, Ukraine;
⁷Department of Protein Structure and Function, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
⁸Department of Obstetrics and Gynecology, Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
⁹Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
*e-mail: sandor.vari@cshs.org

Received: 13 June 2023; Revised: July 2023;
Accepted: July 2023; Available on-line: 11 July 2023

COVID-19 infection, preeclampsia and gestational diabetes mellitus in pregnancy cause similar changes in the placenta and influence development of the fetus between conception and birth in gestation. Proper uterine and placental vascularization is essential for normal fetal development. The transplacental exchange is regulated and maintained by the placental endothelium. During placental implantation, the trophoblast differentiates into two distinct layers, the inner cytotrophoblast and outer syncytiotrophoblast, which are key elements of the human placental barrier. Proinflammatory cytokines exacerbate ischemic events and create an upward spiral of an inflammatory reaction in the placenta. Placental pathology in gestational COVID-19 shows desquamation and damage of trophoblast and chronic histiocytic intervillositis. Similar lesions also occur in gestational diabetes mellitus and preeclampsia. The systemic inflammatory response of the mother, the increased inflammation in the placenta and cytokine production by placental trophoblasts should be monitored throughout pregnancy. Placental angiogenesis can be evaluated by serum vascular endothelial growth factor, Annexin A2, placental growth factor or sclerostin. Tissue damage can be assessed by measuring levels of serum lactate dehydrogenase and myeloperoxidase. Blood flow can be monitored with three-dimensional Doppler and pathological changes can be documented with paraffin-embedded tissue sections stained with hematoxylin and eosin, and electron microscope images as well as immunohistochemistry tests for vascular endothelial growth factor, placental growth factor, sclerostin and Annexin A2. The damage of maternal and fetal vascular perfusion (villitis and fibrin deposition) is a common mechanism of gestational diseases. The placenta lesions liberate anti-endothelial factors that lead to anti-angiogenic conditions and are the common mechanism of maternal placental vascular malperfusion in gestational diseases.