Seminal transforming growth factor (TGF) beta, maternal immune tolerance and pregnancy outcome

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This study aims to determine the extent to which semen is important in initiating the maternal immune response to the fetus and placenta during pregnancy. We postulate that exposure to paternal proteins in sperm and other factors present in the semen may have a cumulative, beneficial effect in 'educating' the female immune system to respond in the correct way to the embryo when pregnancy occurs. To investigate this, the behaviour and movements of white blood cells responding to semen will be studied during the period after mating, in which the uterus prepares for and accommodates to pregnancy. In particular, the study will focus on the roles of a specific chemical messenger substance in semen, called transforming growth factor (TGF)-beta, which triggers the molecular changes leading to maternal immune tolerance. A deeper understanding of these events will have an important impact in human and veterinary medicine where implantation failure is a major cause of reproductive loss and inadequate placental growth poses a threat to the health of the conceptus both in utero and into adult life.