Ran Goshen

Parental imprinting of the human H19 gene

It has only recently become clear that genetic imprinting plays an important role in human embryogenesis and in processes leading to the development of pediatric cancers and other human diseases. Using a unique human tissue, the androgenetic complete hydatidiform mole, we established that the maternally inherited allele of the imprinted H19 gene is expressed. Our results also show that the paternal allele of the human IGF‐II gene, a gene suspected to be parentally imprinted in humans, is expressed.

The role of estrogen support during the luteal phase of in vitro fertilization-embryo transplant cycles: a comparative study between progesterone alone and estrogen and progesterone support

OBJECTIVE To evaluate the possible role for estrogen supplementation to the P luteal phase support of GnRH agonists (GnRH-a)- and hMG-induced IVF-ET cycles. SETTING In vitro fertilization unit in a tertiary care university hospital. DESIGN A prospectively randomized study. PATIENTS One hundred consecutive patients undergoing ET after IVF were assigned into one of two luteal supplementation regimens. INTERVENTIONS In all patients enrolled in the study, ovulation was induced using the midluteal regimen for pituitary down regulation with GnRH-a followed by follicular stimulation with hMG. The first group received IM P 50 mg/d, as luteal phase support, starting the day of ET. The second group received the same dosage of P, combined with oral E2 valerate, 2 mg/d. Serum levels of P and E2 were monitored every 4 days for 16 days after ET. MAIN OUTCOME MEASURES Pregnancy rates (PRs) and live birth rates per ET. RESULTS No significant difference in E2 or P levels throughout the cycle was observed between groups. Similar PRs per ET and the live birth rates were also observed between group A and B (28% versus 26.5% and 78.6% versus 76.1%, respectively). CONCLUSION No advantage was found in the addition of E2 valerate to P luteal phase support of GnRH-a- and hMG-induced IVF-ET cycles.

A growing relationship between genomic imprinting and tumorigenesis

The association between aberrations of the human genome and the development of cancer is well established. Gene imprinting, defined as gene expression based on the gamete of origin, has previously been shown to be involved in this process by the loss of tumor suppressor gene regulation. We suggest that the activation of imprinted proto-oncogenes and growth factors may also play a vital role in tumorigenesis. Mechanistically, this can occur when the gene is removed from its imprinted sequence area, thus escaping repression. Synteny between the human and mouse genome provides the opportunity for targeted studies of imprinted genes suspected to be involved in cancer.

Down's syndrome as a model for the decisive role of maternal lineage in human evolution

The study of human evolution and the mechanism of this process can be approached from physical anthropology, which examines phenotypic expression and molecular evolution, which investigates genotypic change. Alternatively, we suggest that human evolutional process can also be explained using present day examples of abberations in evolution. Thus, from both genotypic and phenotypic perspectives, we address the question of whether Downs syndrome is an instructive example to look into the decisive role of maternal lineage in human evolution.

Morphologic Characteristics of the Interaction Between Normal Cytotrophoblasts and Their Malignant Counterpart in the Development of Trophoblastic Neoplasia

Objectives: To define the biology of the tumor-host cell interaction with regard to cellular kinetics and morphologic changes during cell-cell interaction in an in vitro model of trophoblastic neoplasia. Methods: Using a coculture in vitro system ofcytotrophoblasts and choriocarcinoma cells, we investigated the cellular kinetics and the morphologic changes in these interacting cells. A fully automatic time-lapse image system was used to record phase contrast images of the cocultured cells in a tissue culture chamber. To examine cytoskeletal structure, immunofluorescent-labeled antibodies against intermediate filaments were used. Slides were examined with a confocal laser scanning microscope and subjected to computed analysis. Results: The choriocarcinoma cells attract normal cytotrophoblasts using what resembles pseudopodia to engulf the latter cells and thus form slow-growing colonies. In this process, new hybrid cells are formed, which can be differentiated from their original contributors by morphologic characteristics. Conclusion: This phenomenon supports our previous biochemical and molecular data on the role of cell-cell interaction in the complex process of cytotrophoblast transformation and the development of gestational trophoblastic neoplasia.

The role of genomic imprinting in implantation**Supported by the U.S. Binational Science Foundation and by the Joint Research Fund of the Hebrew University and Hadassah, Jerusalem, Israel.

OBJECTIVES To outline the possible role of the imprinted genes in early human embryogenesis and implantation. DATA IDENTIFICATION Literature review. STUDY SELECTION Studies examining the issues of genomic imprinting, implantation, gestational trophoblastic diseases, placental gene expression, and trophoblast invasion. RESULTS Certain genes have been shown to be expressed either in the embryo or in the uterine decidua before implantation. Some of these have been shown to be parentally imprinted, that is, expressed either from their paternal or maternal origin. The paternally expressed genes are linked to placental proliferation and invasiveness. CONCLUSIONS Clinical and basic data from different disciplines indicate that genomic imprinting may be crucial to the process of implantation.