**2. Physiology of Pregnancy**

Pregnancy induces a number of alterations to maternal physiology for maintaining the correct course of pregnancy and it involves a cascade of processes commencing from fertilization to the establishment of feto-maternal communication and cross-talk mediated via the placenta. Preimplantation conditions, vascularisation, invasion of the embryonic cells to the maternal uterine wall and oxidative stress are the essential regulators in the function of pregnancy events [18]. Prior to implantation, there is a postovulatory surge of circulatory progesterone level that inhibits the proliferation of estrogen-dependent uterine epithelium and induces secretory transformation of uterine glands. In the early stages of development, i.e., ~day 6 of fertilization, the microvilli of the blastocyst interact with the pinopodes of the uterine endometrial luminal epithelium in order to establish apposition, which becomes stable through the increased adherence of the trophectoderm and the uterine luminal epithelium. During this interaction, a range of molecules are secreted from the immune activated cells including mucin, selectin, integrin and cadherin [18,19]. Shortly thereafter, invasion begins and trophectoderm penetrates the uterine epithelium, invading the wall of the uterine arteries where they interact with the cells of the maternal circulatory immune system and mediate the remodeling of the uterine spiral arteries that supply the placenta. This is followed by deportation of aggregates containing transcriptive materials.

There is direct evidence that platelets are involved in the placentation process. During placentation, trophoblasts invade the decidual stroma including the uterine glands and migrate into the maternal uterine spiral arteries replacing the vascular smooth muscle cells to remodel the arteries as low resistance, large caliber vessels [20]. This process ensures adequate placental perfusion by the remodeling of maternal uterine vessels. Histological examination shows deposition of maternal platelets in the trophoblast aggregates formed in the uterine spiral arteries. A number of studies discovered that these platelets are activated, releasing soluble factors enhancing the invasive capacity of trophoblast cells [21]. The trophoblasts produce a range of vasoconstrictors and vasodialators that are in balance to maintain the placental blood flow for proper fetal development during pregnancy [22].

During pregnancy, the viscosity and coagulability of maternal blood upsurges due to the increase in pro-coagulant agents, such as plasminogen activator inhibitor-1, fibrinogen, factor VII, VIII, von Willebrand factor and to the reduced fibrinolysis. The hypercoagulable state is attributed to the activation of platelets [23]. Maternal serum biochemical markers of pregnancy, namely alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol [24] and inhibin-A [25], are produced and found in higher concentration in the maternal peripheral circulation due to the implantation and placentation processes of pregnancy.
