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Member Information
Samuel Parry, MD
Assistant Professor, Department of Obstetrics and Gynecology
Office Phone: 215-573-4916
Office Fax:
Email: parry@mail.med.upenn.edu
Website(s):
Education: MD 1990, Columbia University College of Physicians and Surgeons
Keywords: placenta, trophoblast cells, HIV-1 infections, transcytosis
Research and/or Clinical Interests:
We are studying the mechanisms by which HIV-1 crosses the placenta from the maternal to fetal circulation.
Summary:
Vertical transmission of human immunodeficiency virus (HIV) occurs primarily as the fetus passes through the maternal birth canal. However, transplacental passage of HIV from the maternal to the fetal circulation occurs throughout pregnancy and eludes many of the treatment protocols that have been developed to prevent vertical transmission. Consequently, the factors that mediate transplacental passage of HIV must be elucidated before vertical transmission of HIV can be further reduced, particularly in under-developed regions where the prevalence of seropositivity is highest and current prophylactic strategies against vertical transmission are not available. We hypothesize that the villous trophoblast layer of the human placenta has evolved to resist transplacental transmission of infectious pathogens. However, the placenta appears to be permissive to particular strains of HIV. Therefore, the objectives of our research are: 1) to determine if strains of HIV can infect and cross the syncytiotrophoblast layer, and 2) to investigate the factors that permit the transplacental transmission of particular HIV strains. We are performing transcytosis experiments using confluent villous trophoblast cells cultured on semi-permeable membranes and various HIV-1 isolates from neonatal infections. We use PCR and immunostaining techniques to determine which viral strains can infect and cross the trophoblast layer. Additionally we will attempt to prevent transmission of viral strains to which the trophoblast is otherwise permissive by pretreating the cells with antiviral cytokines or antibodies that block viral receptors. We anticipate that these experiments will provide the first comprehensive analysis of the interactions between HIV and placental trophoblast cells. The mechanisms by which the placenta resists infection by HIV may be incorporated into novel strategies to prevent transmission of HIV.
Representative Publications:
Parry S, Holder J, Strauss III JF. Mechanisms of trophoblast-virus interaction. J Reprod Immunol 1997;37:25-34.
Parry S, Strauss III JF. Premature rupture of the fetal membranes. N Engl J Med 1998;338:663-9.
Parry S, Holder J, Halterman MW, Weitzman M, Davis AR, Federoff H, Strauss III JF. Transduction of human trophoblast cells by replication-deficient recombinant viral vectors: promoting cellular differentiation affects virus entry. Am J Pathol 1998;152:1521-9.
Parry S, Macones GA, Roth NW, Desperito TJ, Marzullo A, Morgan MA. Antiphospholipid antibodies in chronic hypertension: the value of screening during pregnancy. Am J Perinatol 1998;15:527-31.
Parry S, Koi H, Strauss III JF. Gene and viral delivery to the trophoblast. Adv Drug Delivery Rev 1999;38:69-80.
Roberts AK, Monzon-Bordonaba F, VanDeerlin PG, Holder J, Macones GA, Morgan MA, Strauss III JF, Parry S. A polymorphism within the promoter of the tumor necrosis factor-a gene is associated with an increased risk of preterm premature rupture of the fetal membranes. Am J Obstet Gynecol 1999;180:1297-302.
Parry S, Severs C, Sehdev HM, Macones GA, White LM, Morgan MA. Ultrasound prediction of fetal macrosomia: its effect on labor management. J Reprod Med 2000;45:17-22.
Koi H, Zhang J, Makrigiannakis A, Getsios S, MacCalmam CD, Kopf GS, Strauss III JF, Parry S. Differential expression of the coxsackievirus and adenovirus receptor regulates adenovirus infection of the placenta. Biol Reprod 2001;64:1001-9.
Angus SR, Segel SY, Hsu CD, Locksmith GJ, Clark P, Sammel MD, Macones GA, Strauss III JF, Parry S. Amniotic fluid matrix metalloproteinase-8 indicates intra-amniotic infection. Am J Obstet Gynecol 2001;185:1232-8.
Koi H, Zhang J, Parry S. The mechanisms of placental viral infection. Ann NY Acad Sci 2001;943:148-156.
Ferrand PE, Parry S, Sammel M, Macones GA, Kuivaniemi H, Romero R, Strauss III JF. A polymorphism in the matrix metalloproteinase-9 (MMP-9) promoter is associated with increased risk of preterm premature rupture of membranes (PPROM) in African Americans. Molec Hum Reprod 2002;8:494-501.
Arechavaleta-Velasco F, Koi H, Strauss III JF, Parry S. Viral infection of the trophoblast: time to take a serious look at its role in abnormal implantation and placentation? J Reprod Immunol 2002;55:113-21.
Fujimoto T, Parry S, Urbanek M, Sammel M, Macones G, Kuivaniemi H, Romero R, Strauss III JF. A single nucleotide polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter influences amnion cell MMP-1 expression and risk for preterm premature rupture of the fetal membranes. J Biol Chem 2002;277:6296-302.
Ferrand PE, Fujimoto T, Chennathukuzhi V, Parry S, Macones GA, Sammel M, Kuivaniemi H, Romero R, Strauss, III JF. The CARD15 2936insC Mutation and TLR4 896 A>G Polymorphism in African Americans and Risk of Preterm Premature Rupture of Membranes (PPROM).Molec Hum Reprod 2002;8:1031-4.
Koi H, Zhang J, Makrigiannakis A, Getsios S, MacCalman CD, Strauss III JF, Parry S. The syncytiotrophoblast is a barrier to maternal-fetal transmission of herpes simplex virus. Biol Reprod 2002;67:1572-9.
Arechavaleta-Velasco F, Ogando D, Parry S, Vadillo-Ortega F. Production of matrix metalloproteinase-9 in lipopolysaccharide-stimulated human amnion occurs through an autocrine and paracrine proinflammatory cytokine-dependent system. Biol Reprod 2002;67:1952-8.
Arechavaleta-Velasco F, Marchiano D, Díaz-Cueto L, Parry S. Matrix Metalloproteinase-8 is expressed in human chorion during labor. Am J Obstet Gynecol, in press.
Ali AS, Khandelwal M, Zhao J, Mehmet AH, Sammel MD, Parry S. Neutrophils are stimulated by syncytiotrophoblast microvillous membranes to generate superoxide radicals in women with preeclampsia. Am J Obstet Gynecol, in press.
