Perinatal toxicology is the focus of this laboratory. How viruses, metals, anti-HIV therapy, and vitamins (A, B12, C and E) affect normal development of the embryo/ fetus are being investigated. In particular, the role of the placenta as the anchor, controller, and conduit during pregnancy as well as a site for toxic action is examined.

      HIV. Why do only 25-40% of the babies of HIV positive mothers become infected? Why not all the babies? What controls infectivity of the fetus in utero? These are questions being explored in patients who are pregnant and HIV positive. In vitro models of human placenta are used to study how the placenta may modulate HIV infection in utero. Certain strains of HIV-1 can selectively infect the human placenta, while others do not. Molecular technics are being used PCR, ISPCR to determine which cells are being infected. With these models we can test how anti-HIV therapies may best prevent the vertical transmission of HIV as well as produce toxicity in the human placenta. Further studies of the environmental interactions of ethanol exposure and HIV infection are in progress.

      Placental Toxicology. Cadmium can be a placental toxin in rodents by producing fetal death and placental necrosis. Using an in vitro dually perfused human placenta model showed that cadmium also produced necrosis. The response of the cell to cadmium toxicity may be regulated by metallothionein and calmodulin. Different isoforms of metallothionein are being identified via cDNA isolation and in situ hybridization for determination of metallothionein distribution and inducibility in placentae from women exposed during pregnancy to environmental metals

      Implantation Biology. Pregnancy loss due to implantation failures is being examined using an in vitro model consisting of both human trophoblast and endometrium to study the biology of attachment and invasion as well as the influence of hormones, immune factors, and xenobiotics.

Miller RK, Genbacev O, Turner MA, Aplin JD, Caniggia I, Huppertz B. 2005. Human placental explants in culture: approaches and assessments. Placenta. Jul;26(6):439-448. Review.

Dertinger SD, Camphausen K, Macgregor JT, Bishop ME, Torous DK, Avlasevich S, Cairns S, Tometsko CR, Menard C, Muanza T, Chen Y, Miller RK, Cederbrant K, Sandelin K, Ponten I, and Bolcsfoldi G. 2004. Three-color labeling method for flow cytometric measurement of cytogenetic damage in rodent and human blood. Environ Mol Mutagen. 44(5):427-435.

Hoeger KM, Kochman L, Wixom N, Craig K, Miller RK, and Guzick DS. 2004. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril. Aug;82(2):421-429.

Dertinger SD, Chen Y, Miller RK, Brewer KJ, Smudzin T, Torous DK, Hall NE, Olvany KA, Murante FG, and Tometsko CR. 2003. Micronucleated CD71-positive reticulocytes: a blood-based endpoint of cytogenetic damage in humans. Mutat Res. 2003 Dec 9;542(1-2):77-87.

Miller RK, Mace K, Polliotti B, DeRita R, Hall W, and Treacy G. 2003. Marginal transfer of ReoPro (Abciximab) compared with immunoglobulin G (F105), inulin and water in the perfused human placenta in vitro. Placenta. Aug;24(7):727-738.

Polliotti BM, Fry AG, Saller DN, Mooney RA, Cox C, and Miller RK. 2003. Second-trimester maternal serum placental growth factor and vascular endothelial growth factor for predicting severe, early-onset preeclampsia. Obstet Gynecol. Jun;101(6):1266-1274

Yacobi S, Ornoy A, Blumenfeld Z, and Miller RK. 2002. Effect of sera from women with systemic lupus erythematosus or antiphospholipid syndrome and recurrent abortions on human placental explants in culture. Teratology. Dec;66(6):300-308.

Polliotti BM, Gnall-Sazenski S, Laughlin TS, and Miller RK. 2002. Inhibitory Effects of Human Chorionic Gonadotropin (hCG) Preparations on HIV Infection of Human Placenta in vitro. Placenta. Apr;23 Suppl A:S102-106.

Shepard TH, Brent RL, Friedman JM, Jones KL, Miller RK, Moore CA, and Polifka JE. 2002. Update on new developments in the study of human teratogens. Teratology. Apr;65(4):153-161.

Dertinger SD, Torous DK, Hall NE, Murante FG, Gleason SE, Miller RK, and Tometsko CR. 2002. Enumeration of micronucleated CD71-positive human reticulocytes with a single-laser flow cytometer. Mutat Res. 2002 Mar 25;515(1-2):3-14.

Woods JR Jr, Cavanaugh JL, Norkus EP, Plessinger MA, and Miller RK. 2002. The effect of labor on maternal and fetal vitamins C and E. Am J Obstet Gynecol. 2002 Nov;187(5):1179-1183.