Genetic conflicts in human pregnancy.

Abstract

Pregnancy has commonly been viewed as a cooperative interaction between a mother and her fetus. The effects of natural selection on genes expressed in fetuses, however, may be opposed by the effects of natural selection on genes expressed in mothers. In this sense, a genetic conflict can be said to exist between maternal and fetal genes. Fetal genes will be selected to increase the transfer of nutrients to their fetus, and maternal genes will be selected to limit transfers in excess of some maternal optimum. Thus a process of evolutionary escalation is predicted in which fetal actions are opposed by maternal countermeasures. The phenomenon of genomic imprinting means that a similar conflict exists within fetal cells between genes that are expressed when maternally derived, and genes that are expressed when paternally derived. During implantation, fetally derived cells (trophoblast) invade the maternal endometrium and remodel the endometrial spiral arteries into low-resistance vessels that are unable to constrict. This invasion has three consequences. First, the fetus gains direct access to its mother's arterial blood. Therefore, a mother cannot reduce the nutrient content of blood reaching the placenta without reducing the nutrient supply to her own tissues. Second, the volume of blood reaching the placenta becomes largely independent of control by the local maternal vasculature. Third, the placenta is able to release hormones and other substances directly into the maternal circulation. Placental hormones, including human chorionic gonadotropin (hCG) and human placental lactogen (hPL), are predicted to manipulate maternal physiology for fetal benefit. For example, hPL is proposed to act on maternal prolactin receptors to increase maternal resistance to insulin. If unopposed, the effect of hPL would be to maintain higher blood glucose levels for longer periods after meals. This action, however, is countered by increased maternal production of insulin. Gestational diabetes develops if the mother is unable to mount an adequate response to fetal manipulation. Similarly, fetal genes are predicted to enhance the flow of maternal blood through the placenta by increasing maternal blood pressure. Preeclampsia can be interpreted as an attempt by a poorly nourished fetus to increase its supply of nutrients by increasing the resistance of its mother's peripheral circulation.