Research Interests:
Mechanisms of trophoblast-virus interactions
Congenital viral infection is associated with fetal anomalies, postnatal infection, and intrauterine fetal death. Although tansplacental passage of virus is a critical aspect of these infections, few investigators have characterized placental viral infection and what role placental trophoblast cells have in passage of virus from the maternal to the fetal circulation. To define the mechanisms by which placental trophoblast cells influence viral infection, we are studying the interaction of recombinant viral vectors (adenovirus, herpes simplex virus, and human immunodeficiency virus) and wild-type viruses with choriocarcinoma cell lines and primary trophoblast cells. Our findings suggest that trophoblast cellular differentiation leads to alterations in the mechanisms of virus uptake that may discourage or facilitate maternal-fetal transmission. Future experiments will characterize the expression of human immunodeficiency virus receptors within the placenta and the ability of human immunodeficiency virus to infect trophoblast cells. Additionally, we will begin to describe the pathologic sequelae that result from placental viral infection.

Genetic markers for idiopathic preterm delivery
Preterm birth is the leading cause of perinatal deaths among infants without anomalies in the United States. Unfortunately, more than one half of spontaneous preterm deliveries occur in women with no discernible risk factors, including low socioeconomic status, a history of preterm birth, reproductive tract infections, and the presence of fetal fibronectin in cervicovaginal secretions. We are investigating whether genetic factors that govern host inflammatory responses, including polymorphisms within the tumor necrosis factor-A (TNF-A) and interleukin-1 (IL-1) genes, are associated with idiopathic preterm birth. We recently conducted a case-control study of women admitted to our labor floor to determine the frequencies of allelic variants of TNF-A and IL-1 gene polymorphisms. Our results suggest that the rarer allele of a TNF-A polymorphism, which is associated with increased production of TNF-a protein, is significantly more common among women delivering preterm. This study provides the first evidence of a genetic predisposition for preterm birth. We intend to confirm the assocciation of DNA markers (the TNF-A gene) with preterm birth by examining the ability of the TNF-A marker to predict which women with preterm contractions are more likely to deliver preterm, and by combining this genetic marker with environmental factors to best determine a patient's risk for preterm birth. Additionally, we will investigate the affects of TNF-A allelic variants on TNF-a production and extracellular matrix degradation in reproductive tissues. Most importantly, we will begin transmission disequilibrium testing to determine if linkage exists between the TNF-A marker and a candidate gene for preterm delivery.

Recent Representative Publications:
Ferrand PE, Parry S, Sammel M, Macones GA, Kuivaniemi H, Romero R, Strauss III JF. (2002). 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 8: 494-501.

Ferrand, PE, Fujimoto T, Chennathukuzhi V, Parry S, Macones GA, Sammel M, Kuivaniemi H, Romero R, Strauss, III JF. (2002). The CARD15 2936insC Mutation and TLR4 896 A>G Polymorphism in African American and Risk of Preterm Premature Rupture of Membranes (PPROM). Molec Hum Reprod 8: 1031-1034.

Fujimoto T, Parry S, Urbanek M, Sammel M, Macones G, Kuivaniemi H, Romero R, Strauss III JF. (2002). 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 277:6296-6302.

Koi H, Zhang J, Makringiannakis A, Getsios S, MacCalman CD, Strauss, III JF, Parry S. (2002). The syncytiotrophoblast is a barrier to maternal-fetal transmission of herpes simplex virus. Biol Reprod 67:1572-1579.

O'Brien PJ, Koi H, Parry S, Brass LF, Strauss, III JF, Wang LP, Tomaszewski JE, Christenson LK. (2003). Thrombin receptors and protease-activated receptor-2 in human placentation. Am J. Pathol 163:: 1245-1254.

Segel SY, Miles AM, Clothier B, Parry S, Macones GA. (2003). Duration of antibiotic therapy after preterm premature rupture of fetal membranes. Am J Obstet Gynecol 189: 799-802.

Ali AS, Khandelwal M, Zhao J, Mehmet AH, Sammel MD, Parry S. (2004). Neutrophils are stimulated by syncytiotrophoblast microvillous membranes to generate superoxide radicals in women with preeclampsia. Am J Obstet Gynecol 190:252-258.

Arechavaleta-Velasco F, Marchiano D, Diaz-Cueto L, Parry S. (2004). Matrix Metalloproteinase-8 is expressed in human chorion during labor. Am J Obstet Gynecol 190: 843-850.

Macones GA, Parry S, Elkousy M, Clothier, B, Ural S, Strauss, III JF. (2004). The maternal TNF-2 allele and bacterial vaginosis: preliminary evidence of gene environment interaction in the etiology of spontaneous preterm birth. Am J Obstet Gynecol 190: 1504-1508.

Wang H, Parry S, Macones G, Sammel MD, Ferrand PE, Kuivaniemi H, Tromp G, Halder I, Shriver MD, Romero R, Strauss III JF. (2004). Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM). Hum Molec Genet 13: 2659-2669.

Chou D, Ma Y, Zhang J, McGrath CM, Parry S. (2006). Cytomegalovirus infection of trophoblast cells elicits an inflammatory response: A possible mechanism of placental dysfunction. Am J Obstet Gynecol 194: 535-41

Parry S., Zhang, J. (2007). Multidrug resistance proteins affect drug transmission across the placenta. Am J Obstet Gynecol 196: 476 e1-6.

Arechavaleta-Velasco F, Gomez L, Ma J, Zhao, McGrath C, Sammel MD, Nelson DB, Parry S. Adverse
reproductive outcomes in urban women with adeno-associate virus-2 infections in early pregnancy. Human
Reproduction (10); 1-8 October 2007