Fourth World Conference on Early Pregnancy CONTINUUM BETWEEN IMPLANTATION AND PERINATAL EVENTS

Embryo Maternal Dialogue:
Linking Pregnancy Recognition and Proliferation Control

Eytan R. Barnea, MD, FACOG

SIEP Chairman, The Society for the Investigation of Early Pregnancy

Presentation

Embryo-maternal dialogue starts shortly after conception and it is exerted both at a local level and through systemic signaling. Locally, the embryo travelling through the fallopian tube is recognized and tolerated by the mother, consequently, it is not attacked or rejected by the maternal immune system. Specific pre-implantation factors (PIF), discovered by us, are likely to exert such an immune effect. We found that PIF, an embryo derived peptide, affects cellular immune response in vitro. Such immune signaling is also detectable in peripheral sera within few days after fertilization and prior to implantation and is likely also to aid in preparing the endometrium for implantation. Upon implantation, local embryo-endometrial communication becomes direct and highly amplified. The endometrium, while a privileged site, is not an absolute requirement for implantation since systemic pregnancy recognition occurs also in cases of extra-uterine pregnancy. Following few cell divisions, separation between embryonic and extra-embryonic structures take place. The embryo is the carrier of the genome while the surrounding structures provide support while the trophoblast is responsible for the implantation process. Once the embryo?s immune privilege is secured, embryogenesis proper can initiate. Promoters of embryo development has been widely investigated however, knowledge of those compounds that safeguard against abnormal proliferation is limited.

We have further identified a class of embryo-derived novel proteins / peptides, developmental proteins (DPs) that are present in the embryo prior to the development of a local mature immune system. Their role is to create the required balance between proliferation and its control. DPs control abnormal cell proliferation, in a nontoxic manner while not interfering with normal embryonal development. They prevent abnormal growth by eliminating abnormal cells caused by mutations or adverse environment (carcinogens, toxins, viruses, and ionic radiation). DPs may also function by redirecting growth towards functionality through differentiation. DPs appear to act through a specific receptor negating growth factors? effect. Within 2 minutes, they promote tumor suppressors and inhibit tumor promoters, stopping DNA synthesis by 24 hours, followed by programmed cell death, apoptosis - a process well recognized in the developing embryo - by 48 hours. When an embryo becomes incompatible with life, DPs may overcome proliferation promoters by causing embryonic growth arrest. Additionally, for the defective embryo to be rejected, PIF-like compounds must decline as well. Consequently, the immune system by now not altered, consequently pregnancy rejection can be completed, since the immune privilege of the embryo has been lost.

The ongoing final characterization of these embryo-derived compounds (PIF and DPs) will help both in diagnosing and treating early pregnancy disorders, or abnormal proliferation due to cancer or viral infection.

Speaker Declaration: Dual Commitment

Dr. Eytan R. Barnea is founder and chairman of SIEP, the Society for the Investigation of Early Pregnancy (not-for-profit) which publishes EPBM, Early Pregnancy: Biology and Medicine journal (Index Medicus, Medline). As Chief Scientist to enVision biomedical and BioSpectrum, Inc. he is principal investigator/award recipient of the DARPA, the Department of Defense agency R&D grant on Developmental Proteins (DPs) to Counteract Biological Warfare (BW). As Chief Scientist to BioIncept, Inc. he has received from CONRAD, the Contraceptive Research and Development Program administered by the EVMS with coordinated efforts by USAID, NIH, CDC, WHO, a grant for the Antibodies Against Preimplantation Factor (PIF) and their Contraceptive Potential. Several additional grants have been submitted and / or are being thought and additional alliances with major developmental institutions are being implemented.

Dr. Barnea was awarded several patents by the US Patent office and worldwide and is involved in the development of the potential medical treatments thereinof ensuing:

Gestational Agents for Controlling Cell Proliferation (DPs)

Preimplantation Factor (PIF) (w/ C.B. Coulam)

For personal use. Only reproduce with permission from SIEP.