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Placental Proteins, Drug Transport, and Fetal Development

Bethesda, Maryland
August 27 & 28, 2003

NIDA Organizer(s): Pushpa V. Thadani, Ph.D. & Rao Rapaka, Ph.D.

Meeting Purpose and Intent

Use of drugs of abuse during pregnancy is a major public health concern because of potential adverse effects on the fetus and the risk to maternal health. Since the placenta is the primary link between the mother and the conceptus and is essential for fetal growth and development, abnormalities in placental formation and function resulting from drug use and abuse could have a major influence on pregnancy outcome. Pregnancy complications such as preeclampsia, placenta previa and placental abruption seen in the general population, which are associated with adverse or poor fetal outcomes, frequently occur in women who abuse drugs during pregnancy, which represents a major public health concern. The clinical literature to date reports that infants born of mothers who used drugs, licit and illicit, have impaired somatic growth and development as well as neurobehavioral deficits. Other studies show that cocaine, marijuana, heroin and other abused drugs can cross the placental barrier. However, at present little information is available on the impact of abused drugs on placental biology alone or in combination with other 'host' factors such as poor prenatal care, stress, infection, and poor maternal nutrition, which are common co-morbid factors in drug abusing women.

Recent advances in the field of placental biology and the limited investigation of drugs of abuse related to placental development prompted the National Institute on Drug Abuse (NIDA) to assemble a group of biomedical researchers to discuss cutting-edge research with the mission of translating these findings to clinical application and to identify technologies that could facilitate research on the effects of drugs of abuse on placental function. The research areas covered in the conference included the development of the placenta, its role in immune-endocrine interactions during pregnancy, its function in the transfer of molecules (transporter systems), and the influence of infectious agents and xenobiotics on placental biology.


Brief Discussion of Meeting Outcome

Since the objective of this workshop was to identify gaps in our knowledge and topics for future research and how current technology could advance NIDA's mission, the discussion centered on emerging research in the drug abuse field related to placental physiology. Although existing data clearly suggest that drugs of abuse do produce alterations in placental function that can adversely affect the fetus, a number of key issues require attention. Workshop participants identified the following deficiencies in our knowledge base and made recommendations for a research agenda to address these deficiencies. Additional studies were recommended to:

  1. Gain information as to how 'host' factors including genetic variation, recreational drug use, infection and malnutrition influence the placental barrier and its function;
  2. Determine how the embryo/fetus is protected in different compartments;
  3. Characterize the cellular and molecular processes involved in the transport of drugs and other molecules by various transport systems;
  4. Study interactions of the endocrine and immune systems, both from a maternal and fetal perspective, as well as related to placental development and the impact of drugs of abuse;
  5. Elucidate the effects of drugs of abuse on growth and angiogenic factors using animal and model cell systems;
  6. Develop new technology to examine drug distribution and pharmacokinetics in vivo in small animals;
  7. Identify biomarkers in biological fluids (serum, urine, saliva) and placental tissue that can be used to assess drug exposure in pregnant women using newer tools of genomics and proteomics.

It was believed that ultimately, studies addressing these needs would generate information that would advance our understanding as to how the development of the placenta is affected by drugs of abuse alone or in combination with other host factors, and how these effects relate to the growth and development of the fetus and postnatal health.


Expected Follow-up

Publicize the report and encourage researchers to submit proposals.


Brief Description of Resulting Publications

The conference report was published in Am. J. Obstet. Gynecol. in 2004, volume 191(6): 1858-1862. "National Institute on Drug Abuse Conference Report on Placental Proteins, Drug Transport, and Fetal Development" Pushpa V. Thadani, Jerome F. Strauss, Sudhansu K. Dey, et al.



August 27, 2003

8:30 a.m. Pushpa Thadani, Ph.D. (Chair)
Rao Rapaka, Ph.D. (Co-Chair)

Welcome and Introduction
8:40 a.m. Nora Volkow, M.D.
Director, National Institute on Drug Abuse
9:00 a.m. Jerome Strauss, M.D., Ph.D.
9:30 a.m. James Cross, D.V.M, Ph.D.
Molecular Mechanisms Underlying the Development of the Placenta
10:15 a.m. Daniel Linzer, Ph.D.
Placental Hormones and The Control of Hematopoiesis
11:00 - 11:30 a.m. Break
11:30 a.m. Kenneth Audus, Ph.D.
Placental Drug Metabolism and Adaptation to Drug Exposure in Pregnancy
12:15 p.m. Jashvant Unadkat, Ph.D.
Maternal & Placental P-Glycoprotein Expression, Activity & Regulation During Pregnancy
1:00 - 2:00 p.m. Lunch on your own
2:00 p.m. Vadivel Ganapathy, Ph.D.
Relevance of Placental Monoamine and Organic (C and A) Transporters to Drug of Abuse
2:45 p.m. Donald Novak, M.D.
Maternal: Fetal Amino Acid Flux Share and Share Alike?
3:15 p.m. Yoel Sadovsky, M.D.
Gene Expression in Normal and Abnormal Placenta
4:00 - 4:15 p.m. Break
4:15 p.m. Sudhansu Dey, Ph.D.
Cannabinoid Signaling During Early Pregnancy
5:00 - 5:30 p.m. General Discussion
5:30 p.m. Adjourn

August 28, 2003

8:30 a.m. Michael Soares, Ph.D.
The Maternal-Fetal Interface, Invasive Trophoblast Cells, and Pregnancy-Specific Cytokines
9:15 a.m. Adrian Erlebacher, M.D., Ph.D.
Immune-Endocrine Interactions in A Murine Model of Early Pregnancy Loss
10:00 a.m. Karen Coats, Ph.D.
Proinflammatory Cytokine Expression in the Full-term Placentae of FIV Infected and Uninfected Cats
10:45 - 11:15 a.m. Break
11:15 a.m. Virginia Anderson, M.D.
Transplacental Effects of Viral Agents and Abused Substances on Placental Function and Fetal Development
12:00 noon Richard Miller, Ph.D
Substance abuse, environmental toxins and fetal & postnatal Development
12:45 - 1:45 p.m. Lunch on your own
1:45 p.m. Carolyn Salafia, M.D.
Changes in Gross Placental Morphology Associated with Substance Use
2:30 - 4:00 p.m. Pushpa Thadani, Ph.D., Rao Rapaka, Ph.D.,
Jerome Strauss, M.D., Ph.D., Sudhansu Dey, Ph.D.

General Discussion, Summary & Future Research Directions
4:00 p.m. Adjourn


Participants List

Virginia M. Anderson, M.D.
Associate Professor
Department of Pathology
SUNY Downstate Medical Center
Basic Science Building, Room 4-5

450 Clarkson Avenue, Mail Box 25
Brooklyn, NY 11203
Phone # 718-270-4575
Fax # 718-270-3313
Kenneth L. Audus, Ph.D.
Professor and Chairman of Pharmaceutical Chemistry
The University of Kansas

2095 Constant Avenue
Lawrence, KS 66047-3729
Phone # 785-864-3609
Fax # 785-864-5736
Karen S. Coats, Ph.D.
Associate Professor
Department of Biological Sciences
Mississippi State University

PO Box
Mississippi State, MS 39762
Phone # 662-325-8252
Fax #
James C. Cross, D.V.M., Ph.D.
Departments of Biochemistry and Molecular Biology and Obstetrics and Gynecology
The University of Calgary

Room 2221 Health Sciences Center
3330 Hospital Drive, N.W.
Calgary, Alberta
Canada T2N 4N1
Phone # 403-220-6876 / 7243
Fax # 403-270-0737
Sudhansu K. Dey, Ph.D.
Department of Pediatrics and Cell and Developmental Biology and Pharmacology,
Division of Reproductive and Developmental Biology,
Vanderbilt University School of Medicine

Nashville, TN 37232-0146
Phone # 615-322-8642
Fax #
Adrian Erlebacher, M.D., Ph.D.
Harvard University School of Public Health
Public Health Campus

Boston, MA 02460
Phone # 617-432-0924
Fax # 617-432-0084
Vadivel Ganapathy, Ph.D.
Professor and Vice Chairman
Department of Biochemistry and Molecular Biology
Medical College of Georgia

Augusta, GA 30912
Phone # 706-721-7652
Fax # 706-721-6608
Daniel I. Linzer, Ph.D.
Dean, Weinberg College of Arts and Science
Department of Biochemistry, Molecular Biology and Cell Biology
Northwestern University

633 Clark Street
Evanston, Illinois
Phone # 847-491-3276
Fax # 847-467-1757
Richard K. Miller, Ph.D.
Professor and Associate Chair
Department of Obstetrics and Gynecology
University of Rochester
School of Medicine and Dentistry

Room 5-7550
601 Elmwood Avenue
Rochester, NY 14642-8668
Phone # 585-275-2520
Fax # 585-756-5721
Donald A. Novak, M.D.
Associate Professor
Department of Pediatrics
University of Florida

Gainesville, FL 32611
Phone # 352-392-6410
Fax # 352-846-2147
Yoel Sadovsky, M.D.
Associate Professor
Departments of Obstetrics and Gynecology and Cell Biology and Physiology
Division of Maternal Fetal Medicine and Ultrasound
Washington University School of Medicine

Box 8064
4566 Scott Avenue
St. Louis, MO 63110
Phone # 314-747-0937
Fax # 314-747-1256
Michael Soares, Ph.D.
Institute of Maternal-Fetal Biology
University of Kansas Medical Center

3901 Rainbow Blvd
Kansas City, KS 66160
Phone # 913-588-5691
Fax # 913-588-8287
Jerome F. Strauss, III, M.D., Ph.D.
Center for Research on Reproduction and Women's Health and Department of Obstetrics and Gynecology
University of Pennsylvania Medical Center

1355 Clinical Research Building
421 Curie Boulevard
Philadelphia, PA 19104-6142
Phone # 215-898-0147
Carolyn Salafai, M.D.
EarlyPath Clinical and Research Consultation Services
Assistant in Clinical Psychiatry
Department of Psychiatry
Columbia University College of Physicians and Surgeons

New York, NY
Phone # 914-834-2598/2476
Fax #
Jashvant Unadkat, Ph.D.
Department of Pharmaceutics and Research Affiliate
University of Washington

Box 357610
Seattle, WA 98195
Phone # 206-543-9434
Fax # 206-543-3204

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