2nd Annual Sage Conference
March 8-11, 2001
Winston-Salem, North Carolina

A proceeding was published following this meeting. E-mail info@womenshealthresearch.org to order a hardcopy of this report or click here to view the PDF.

Meeting Summary

The Society for Women’s Health Research held its second annual conference on Sex and Gene Expression (SAGE II) on March 8-11, 2001. SAGE II was a forum for basic research scientist and clinicians to share data and ideas, and foster collaborations relating to the molecular and cellular biology of sex differences. Graduate students, postdoctoral fellows, and distinguished scientists from institutions, hospitals, government, and pharmaceutical industry were among the eighty participants. This interdisciplinary gathering of scientists interested in sex and gene expression was made possible by generous grants from Aventis Pharmaceuticals, Inc. and The David & Lucille Packard Foundation.

SAGE II commenced with welcoming remarks from Phyllis Greenberger, M.S.W., President and CEO, and Sherry Marts, Ph.D., Scientific Director, of the Society for Women’s Health Research. Florence Haseltine, M.D., Ph.D., co-founder of the Society, Denise Faustman, M.D., Ph.D., incoming chair of the Society’s Board, and Julia Amadio, M.B.A., from Aventis Pharmaceuticals spoke briefly about the history of the Society and the importance of sex-based research in the advancement of women’s health.

The first panel of the conference, moderated by Timothy Bestor, Ph.D., from Columbia University, focused on sex differences in development. Dr. Bestor presented data on DNA methyltransferase-1 (DNMT-1) and its influence on genomic imprinting, the process by which selective genes are silenced depending on their maternal or paternal origin. Dr. Bestor reported that a DNMT-1 deletion mutation removes all DNMT1 protein from the mouse oocyte, resulting in developmental abnormalities of future generations. These data suggest that DNMT-1 protein provides maintenance DNA methylation, critical for genomic imprinting and early development.

Panelist Jacquetta Trasler, M.D., Ph.D., from McGill University, stated that 30 million sites in the mammalian genome are methylated at non-random sequence- and sex-specific sites. Dr. Trasler is interested in the 40 or so imprinted genes that show sex-specific methylation. She presented data suggesting that paternal and maternal alleles of certain genes are imprinted at different times during early development, findings that could have an impact on reproductive alternatives.

Panelist Ellen Silbergeld, Ph.D., from University of Maryland, reported that lead may cause reproductive toxicity by binding to human protamines, cysteine-rich zinc binding proteins that pack and protect mammalian sperm DNA. Lead bound at zinc sites in protamine may change the structure of the protein and affect its binding to DNA.

In a panel focusing on sex differences in cognitive development, moderator Marc Tetel, Ph.D., from University of Massachusetts, Amherst, reported on nuclear receptor coactivators, proteins that enhance transcriptional activity of steroid hormones. Dr. Tetel pointed out that steroid hormones influence memory and cognition, and act in the brain to regulate development and behavior. Dr. Tetel presents data showing that steroid receptor coactivator-1 (SRC-1) and CREB binding protein (CBP) is essential for estrogen receptor function in the rat brain.

Judith Ross, M.D., from Thomas Jefferson University presented her work on Turner’s Syndrome, a human genetic disorder associated with the absence of the second X chromosome in females. Dr. Ross reported that estrogen deficiency not only contributes to ovarian failure but also to cognitive deficits, indicating that cognitive function in Turner’s Syndrome has both a genetic and hormonal influence.

Sheri Berenbaum, Ph.D., from Southern Illinois University discussed sex differences in human cognitive and social behavior and how these differences are affected by sex hormones present during prenatal development. Much of her evidence comes from studying girls with congenital adrenal hyperplasia (CAH), an endocrine disorder affecting females who were exposed to elevated androgens during the prenatal period. CAH females have higher spatial ability and are more interested in boy’s toys and activities than girl’s toys. However, she states that women and girls with CAH identify happily as females. Dr. Berenbaum is currently investigating the neural and psychological mechanisms that mediate these behavioral effects, and suspects these mechanisms to be complex.

The next set of speakers explained their use of maternally inherited mitochondrial DNA (mtDNA) and paternally inherited Y chromosome to understand population genetics, human evolution and disease. Douglas Wallace, Ph.D., from Emory University School of Medicine kicked off the session with a lecture entitled, "Mitochondrial Variation in Human Evolution and Disease." Molecular analysis of the mtDNA permitted Dr. Wallace and colleagues to reconstruct ancient human migrations and to identify clinically relevant mtDNA mutations, such as those found to cause Leber’s Hereditary Optic Neuropathy. Dr. Wallace reported the existence of 39 mtDNA genomes, representing the major mtDNA lineages. He also stated that all human mtDNA belong to a single tree, originating in Africa approximately 150,000 years ago.

Mark Seielstad, Ph.D., from Harvard University School of Public Health, moderator of the population genetics panel, presented data on the use of mtDNA and the Y chromosome to understand the female verse male differences in population structure, and the effect of these differences on mitochondrial and Y-chromosome variation. He found that in the populations he studied, women migrated longer distances than men, probably due to cultural circumstances requiring wives to move to their husband's homeland.

David Goldstein, Ph.D., from University College of London uses mtDNA and the Y chromosome to study demographic histories of males and females. He reported that males and females from populations in Europe, Eurasia, and Africa have different demographic histories, and that no simple generalization can be made.

Mark Stoneking, Ph.D., from Max Planck Institute for Evolutionary Anthropology uses mtDNA and Y-chromosome to understand the origins of Polynesians. Dr. Stoneking presented his “slow-boat” model hypothesizing that Polynesian ancestors migrated from Asia/Taiwan through Melanesia into Polynesia. He suggests that Polynesian ancestors mixed extensively with Melanesians, leaving behind their genes and incorporating many Melanesian genes.

The panel on mitochondrial diseases included moderator Douglas Wallace, John Shoffner, M.D., from the Scottish Rite Children’s Hospital, and Gary Gibson, Ph.D. from Weill Medical College of Cornell University. Dr. Wallace presented information on the relationship between oxidative stress, apoptosis, and mitochondrial oxidative phosphorylation, the process that provides cells with vital energy in the form of ATP. He states that cells short on energy and high on stress undergo apoptosis, a cell death pathway used to prevent the initiation of disease.

Dr. Shoffner research focuses on the clinical and genetic aspects of oxidative phosphorylation diseases, most of which are caused by mtDNA mutations. Dr. Shoffner concentrated his talk on Leigh’s Disease, one of the almost 100 known mitochondrial disorders, and the easiest mitochondrial disorder to recognize. Dr. Shoffner presented cases of Leigh’s Disease, illustrating the diagnostic and genetic counseling complexities of oxidative phosphorylation diseases.

Dr. Gibson’s research focuses on the interaction of oxidative metabolism with brain function and dysfunction in disease and aging. Dr. Gibson presented his research on mitochondrial abnormalities in Alzheimer’s Disease (AD), the world’s most common form of dementia. Gibson stated that both men and women are equally affected by AD but the number of women with AD is higher because women out-live men on average. Gibson reported that mutations of mitochondrial proteins that lead to AD make cells more sensitive to oxidative stress, resulting in plaques, tangles, and loss of memory.

Donald Pfaff, Ph.D. from Rockefeller University presented a plenary lecture entitled Neuroendocrine Mechanisms Underlying Hormonal Effects on Arousal: Molecular and Genetic Approaches. Dr. Pfaff’s lecture included studies of environmental, neural, hormonal and genetic contributions to fluctuations in arousal. He believes this research will enrich our understanding of women’s health, especially as it regards basic elements of cognitive function, feelings and mood.

The last panel of the conference focused on the interaction of genotype and the environment in complex diseases. Moderator Craig Hooper, Ph.D., from Centers for Disease Control presented data indicating that cardiovascular disease (CD) may be influenced by genetics, sex, and ethnicity. He reported that exogenous hormones such as estrogen can also influence disease development, and that CD may be initiated or accelerated by other diseases such as diabetes and obesity.

Molly Bray, Ph.D., from University of Texas-Houston presented her research on the genetic and environmental interactions in cardiovascular disease, obesity, hypertension, and diabetes. She is currently characterizing 25 variant loci for environmental effects, such as diet, obesity, physical activity, smoking, menopause status, and hormone use. The loci were chosen from candidate genes thought to be involved in lipid and energy metabolism, blood pressure regulation, and the control of body mass and composition.

Frits Rosendaal, M.D., from Leiden University Medical Center talked about how the interaction between genes and the environment, such as exogenous hormones, may predispose women to venous thrombosis, the blockage of a vein by a blood clot, typically occurring in the leg. Rosendaal reported that women are at increased risk of venous thrombosis during and after pregnancy, or if they are on oral contraceptives or hormone replacement therapy.

Huntington Willard, Ph.D. from University Hospitals of Cleveland and Case Western Reserve University gave the closing plenary lecture on X-inactivation, the process of transcriptionally silencing most genes on one of the two X chromosomes in the female. Dr. Willard’s group has set out to determine the X inactivation profile of all the genes on the X chromosome, an undertaking that he believes will provide relevant information for clinical cytogenetics and counseling, as well as insight into X chromosome organization and the genetics of sexual dimorphism.

In addition to panel and plenary sessions, the conference had three poster sessions, Issues in Early Development, Sex-Specific Genetics and Mitochondrial Diseases, and Sex and Gene Expression: Focus on Complex Diseases. The planning committee judged the posters and awarded Theodore Rasmussen, Ph.D. with the award for best poster, and Laura Carruth, Ph.D. and Mark Hiller, Ph.D., with honorable mention. Congratulations to the winners and thanks to all the participants.

SAGE II brought together an interdisciplinary mix of scientists, creating an interactive, informative, and interesting environment for the exchange of information relating to the molecular and cellular basis of sex differences. Such a forum is sure to strengthen the field of sex-based biology and women’s health and to change the face of medicine.