Preeclampsia severe, megaloblastic macrocitic anemia, infection by zika virus and marginal insertion of umbilical cord affected to patient of 26 years old who showed fetal death to 22 weeks of pregnancy. Light microscopy was applied to the study of her placenta. Stem villi were observed with syncytial hyperplasia, congested vessels, dilated regions in their trajectory, changes in the thickness of the syncytium or interruptions, scanty development of muscular layer in stromal vessels, immature intermediate villi with aneurysms, mature intermediate villi with scarcity of terminal villi, terminal villi with interrupted syncytium and bad development of ramifications of the placental villi which impede the normal interchange of gases or nutrients. These complications of the pregnancy have provoked severe degenerative changes in the placental villous tree that affected the immature and mature intermediate villi with scarcity of terminal villi which have contributed with the death early of the fetus.
Preeclampsia. Macrocitic anemia. Zika virus. Marginal insertion
The placenta can be affected by changes that occurs in the mother or in the formation of their structure. Maternal diseases and eccentric or marginal cord insertion are factors that can to change the histo-architecture of the placental villi (1). Preeclampsia severe, megaloblastic macrocitic anemia, infection by zika virus (Zikv) at 14 weeks of pregnancy and marginal insertion of the umbilical cord affected to pacient of 26 years old who showed fetal death to 22 weeks of pregnancy. It has been described that during preeclampsia the following placental lesions have been mentioned in the literature: infarcts, intervillous thrombi, abruptio, decidual necrosis, abnormal cord insertion, Tenney-Parker changes and retarded growth (2). With hematological disorders the placenta can to present Tenney-Parker changes, infarcts, increased fibrin, abruptio, and villous edema (3). Increased fibrinoid deposition intravillous or perivillous, trophoblastic necrosis, stroma with dilated and replete vessels, endothelial necrosis, sclerosis, stromal disorder by hidropic edema, calcification and terminal villi deficiency were observed when there are placental perfusion bad (4). The effect of anemia on the placenta results in compensatory placental hypertrophy or highly significant placental enlargement in some cases (5). Chronic hypoxia can to provoke capillaries more numerous, thinner and villous length reduced (6). Zika virus produces in stem villi peripheric degenerative changes with collapsed vessels, Tenney-Parker changes or conglomerate of syncytial knots, immature intermediate villi and fibrinoid deposition with macrophages together in Hoffbauer channels, necrosis of the syncytium and stromal fibrosis. Koylocytic cell, destroyed villi, damage in the wall of the vessels and mature intermediate villi with scarcity of terminal villi were also found (7). Marginal insertions may be more susceptible to vessel rupture or compression (8) and have been associated with fetal growth retardation and stillbirth when placental maturation is unevenly accelerated because of low utero placental blood flow (9). Peripheral insertion is related with thrombosis, and these can lead to mural necrosis of vessels with calcification (10). This type of chorionic insertion is associated with fewer penetrating arteries, fewer cotyledons and abnormal umbilical artery blood flow (11). To describe the changes provoked by these four factors on the structure of the placental tissue with light microscope is our proposal.
Material and Methods
Two groups of population of placental villi were taken of placenta study and placenta normal. The group study proceed from hospitable institution whose placenta was obtained to the 22 weeks of pregnancy. Woman pregnancy of 26 years old in come to the hospital with renal insufficiency, preeclampsia severe, megaloblastic macrocitic anemia, infection by Zikv at 14 weeks of pregnancy and with eccentric insertion of the umbilical cord observed after delivery. Zikv was confirmed by nucleic acids detection by RT-PCR. The serology of patient with placenta study was negative for hepatitis B, C, cytomegalovirus, Epstein Barr virus, rubella and toxoplasmosis. The newborn was born alive at 22 weeks and died 4 hours after. The infected woman pregnancy persisted with Zikv infection during five days and had knowledge of informed consent and approval by the ethical committe of the hospitable institution for the realization of this investigation according to the Helsinki declaration. The placenta normal was obtained at 38 weeks of patient with an increase of weight of 10 kg without antecedent of disease. Of each placenta were taken five small specimens of the maternal surface selected at random from the region central parabasal in the vertical plane. Three slides by specimen were prepared for light microscopy and 30 histological slides in total were stained with H&E for their observation.
Stem villi near of decidual region are observed with notable syncytial hyperplasia. Stromal vessels are replete of erythrocytes and others are emptyed (Fig.1). Any stem villi showed congested vessel with dilated region in their trajectory (Fig. 2). Small stem villi exhibit changes in the syncytium and their stromal region is noted in degeneration (Fig. 3). Immature intermediate villi were observed with aneurysms in their vessels which are observed dilated (Fig. 4). Interruptions of the syncytium in small stem villi can be seen with frecuency and scanty development of muscular layer in stromal vessels (Fig. 5). Bad development of small stem villi with dilated vessels occupying almost all the stromal region are noted (Fig. 6). Small stem villi was seen with degenerated syncytium and dilated vessels in stromal region emptyed (Fig. 7). Terminal villi also were seen with interruption of the syncytium and stromal erythrocytes being extruded to the intervillous space (Fig. 8). A general observation of the placental villi permit to us to see bad development of the stem villi (Fig. 9).
During preeclampsia the typical feature of the placental villi is of preterm maturation with long, twisted, partly branched terminal villi that are aggregated around the hidden mature intermediate villi. Severe alteration of terminal villous capillarization occurs showing local variations of non-branching to prevalent branching angiogenesis. Small cross sections of highly capillarized terminal villi can be seen in this complication (1). In our case the activity of zika virus could to be provoking the interruption of the syncytium in these terminal villi. The transfer of throphoblast is increased during preeclampsia probably produced by biochemical changes in the basal membrane that support their structure. Insufficiency arterial uteroplacental in preeclampsia leads to placental isquemic villi by thrombosis of spiral artery (12). Both events have affected with severity the stem villi. Alterations of the placenta are much more extensive during preeclampsia as syncytial knots, infarcts, abruption, proliferation of cytotrophoblast and basal membrane increased which explain the syncytial hyperplasia observed (13). Congested and dilated vessels are consequence of high blood pressure by disorder hypertensive in these patients. Zika virus contains molecules that produces a destructive effect on the placental structure (7) and leads to apoptosis induction (14). Zika viral proteins NS2A, NS2B and NS3 induce apoptosis and protein NS1 possibly damages the endothelial cells through anti-NS1 antibodies (15). Stromal region which was observed almost emptyed in some placental villi showed this viral activity. Some stromal vessels have exploded by high blood pressure provoking severe degenerative changes. The combined effect of Zikv and high bood pressure have produced a general disorganization of the structure of the stem villi. Severe damage in the vessels of stem villi also has been observed in placenta infected by viruses of the togaviridae family which belong the Chikungunya virus (16). In general the viruses appears affect the structure of vessels as has been showed in others works where the placental villi was infected by HIV-HPV (17) or by Cytomegalovirus infection (1). Lysis of the syncytial plasma membrane by the Zikv could produce holes on it and the entrance of fluids to the stromal region since the intervillous space disorganize it. Zika viral proteins functioning as proteases can to lysis the stroma of placental villi (7). Bad development of stem villi, madure intermediate villi with scarcity of terminal villi and interrupted syncytium are morphological abnormalities not considered for the good functioning of the placental villi in the processes of interchange of gases or nutrients (1). Aneurysmal prolongations in the vessels of immature intermediate villi is a consequence of high blood pressure. The scanty development of muscular layer in stromal vessels is caused by the marginal insertion that can to produce cotyledons that have one artery and one vein, with bad perfusion, associated to megaloblastic macrocitic anemia and low arterial blood flow (11). Scarcity of terminal villi with interruption of their syncytium have contributed in part with the death of the fetus at 22 weeks of pregnancy. In conclusion, a serie of complications during pregnancy as preeclampsia, megaloblastic macrocitic anemia, infection by Zikv and marginal insertion of umbilical cord have provoked severe degenerative changes in the placental villous tree that affected the immature intermediate villi, madure intermediate villi and terminal villi which have contributed with the death early of the fetus.
- Benirschke K, Kaufmann P. Pathology of the Human Placenta. 4ed. New York: SpringerVerlag, 2000.
- Soma H, Yoshida K, Mukaida T, Tabuchi Y. Morphologic changes in the hypertensive placenta. Contrib Gynecol Obstet. 1982; 9:58-75.
- Dunn DT, Poddar D, Serjeant BE, Serjeant GR. Fetal haemoglobin and pregnancy in homozygous sickle cell disease. Br J Haematol. 1989;72 (3):434-438.
- Castejón O, Molinaro M, Rivas A, Scucces M, Quiroz V, Graterol I. La vellosidad placentaria en caso de anemia drepanocítica. Rev Obstet Ginecol Venez. 2003; 63(2): 107-114.
- Beischer NA, Sivasamboo R, Vohra S, Silpisornkosal S, Reid S. Placental hypertrophy in severe pregnancy anaemia. J Obstet Gynaecol Br Commonw. 1970; 77(5):398-409.
- Jackson MR, Mayhew TM, Haas JD. Effects of High Altitude on the vascularization of Terminal Villi in Human Placenta. In trophoblast Research, Vol 3, P. Kaufmann and RK Miller eds, pp 351- 360. New York: Plenum, 1988.
- Castejón OC. Zika virus affects the placental villi. BMR Medicine. 2016; 3 (1): 1-6.
- Cordero DR, Helfgott AW, Landy HJ, Reik RF, Medina C, O'Sullivan MJ. A non-hemorrhagic manifestation of vasa previa: a clinicopathologic case report. Obstet Gynecol. 1993; 82 (4 Pt 2 Suppl):698-700.
- Salafia CM, Vintzileos AM. Why all placentas should be examined by a pathologist in 1990. Am J Obstet Gynecol. 1990; 163(4 Pt 1):1282-1293.
- Lewis S, Perrin E. Pathology of the placenta. 2da Edición. New York: Churchill Livingstone, 1999.p.124.
- Nordenvall M, Ullberg U, Laurin J, Lingman G, Sandstedt B, Ulmsten U. Placental morphology in relation to umbilical artery blood velocity waveforms. Eur J Obstet Gynecol Reprod Biol. 1991; 40(3):179-190.
- Redman CWG, Sargent IL, Starkey PM. La placenta humana: Guía para perinatólogos. Barcelona: Masson SA, 1995. pp. 340, 354-355.
- Fox H. The placenta in maternal disorder. In pathology of the placenta. London: WB Sauders, 1978. pp. 214-222.
- Frumence E, Roche M, Krejbich-Trotot P, ElKalamouni C, Nativel B, Rondeau P, Missé D, Gadea G, Viranaicken W, Desprès P. The South Pacific epidemic strain of Zika virus replicates efficiently in human epithelial A549 cells leading to IFN-β production and apoptosis induction.Virology. 2016; 493: 217-226.
- Wong SS, Poon RW, Wong SC. Zika virus infection-the next wave after dengue? J Formos Med Assoc. 2016; 115(4):226-242.
- Castejón OC. The placenta in a case of pregnant woman infected by Chikungunya virus. J Virol Retrovirol. 2016; 2(1): 1-4.
- Castejon OC, Lopez GAJ. The placenta infected by HIV and HPV. Electron J Biomed. 2013; 3: 28- 35.