Formation and development of the placenta

The placenta is the organ of respiration, nutrition and fetal excretion. It produces hormones that ensure normal life of the mother and protect the fetus from immunological aggression from the mother, preventing its rejection, including by preventing the passage of maternal immunoglobulins of class G (IgG).

[1], [2], [3], [4], [5], [6]

Development of the placenta

After implantation the trophoblast begins to expand rapidly. The completeness and depth of implantation depends on the lytic and invasive ability of the trophoblast. In addition, already in these terms of pregnancy, trophoblast begins to secrete HG, PP1 protein, growth factors. From the primary trophoblast, two types of cells are distinguished: cytotrophoblast - inner layer and syncytiotrophoblast - the outer layer in the form of a symplast and this layer is called "primitive" or "prevorsing forms." According to some researchers, the functional specialization of these cells has already been revealed in the prevorsing period. If syncytiotrophoblast is characterized by invasion into the depth of the endometrium with damage to the wall of the capillaries and venous sinusoids, then the primitive cytotrophoblast is characterized by proteolytic activity with the formation of cavities in the endometrium, where the mother erythrocytes come from the destroyed capillaries.

Thus, during this period around the submerged blastocyst there are numerous cavities filled with maternal erythrocytes and a secret of the destroyed uterine glands - this corresponds to the prevorsing or lacunar stage of development of the early placenta. At this time, active rearrangements are taking place in the endoderm cells, and the formation of the embryo and extra-embryonic formations, the formation of amniotic and yolk vesicles, begins. Proliferation of primitive cytotrophoblast cells forms cell columns or primary villi, covered with a layer of syncytiotrophoblast. The appearance of primary villi in terms of time coincides with the first absent menstruation.

On the 12-13th day of development, the transformation of primary villi into secondary ones begins. At the 3rd week of development, the process of vascularization begins, as a result of which the secondary villi turn into tertiary villi. Piles are closed with a continuous layer of syncytiotrophoblast, they have mesenchymal cells and capillaries in the stroma. This process is carried out along the entire circumference of the embryo sac (ring-shaped chorion, according to ultrasound), but more so where the villi touch the implantation pad. At this time, the reservoir of provisional organs leads to the bulging of the entire embryo sac into the lumen of the uterus. Thus, by the end of 1 month of pregnancy, the circulation of embryonic blood is established, which coincides with the onset of cardiac contraction of the embryo. In the embryo there are significant changes, there is a rudiment of the central nervous system, blood circulation begins - a single hemodynamic system was formed, the formation of which is completed by the 5th week of pregnancy.

From 5-6 weeks of pregnancy there is an extremely intensive formation of the placenta, as it is necessary to ensure the growth and development of the embryo, and for this it is necessary, first of all, to create the placenta. Therefore, during this period, the pace of development of the placenta is faster than the rate of embryo development. At this time, the developing syncytiotrophoblast reaches the spiral arteries of the myometrium. The establishment of utero-placental and placental-embryonic blood flow is the hemodynamic basis for intensive embryogenesis.

Further development of the placenta is due to the formation of intervillar space. The proliferating syncytiotrophobia cytotrophoblast lining the spiral arteries, and they transform into typical utero-placental arteries. The transition to placental circulation takes place by 7-10 weeks of gestation and is completed by 14-16 weeks.

Thus, the I trimester of pregnancy is a period of active differentiation of the trophoblast, the formation and vascularization of the chorion, the formation of the placenta and the connection of the embryo with the maternal organism.

The placenta is fully formed by the 70th day from the moment of ovulation. By the end of pregnancy, the mass of the placenta is V, based on the weight of the child's body. The blood flow velocity in the placenta is approximately 600 ml / min. During pregnancy, the placenta "grows old," which is accompanied by the deposition of calcium in the villi and fibrin on their surface. The deposition of excess fibrin can be observed in diabetes mellitus and rhesus-conflict, resulting in poor nutrition of the fetus.

The placenta is the provisional organ of the fetus. In the early stages of development, her tissues differentiate at a more accelerated pace than the embryo's own tissues. Such an asynchronous development should be considered as an expedient process. After all, the placenta must ensure the separation of maternal and fetal blood streams, create immunological immunity, ensure the synthesis of steroids and other metabolic needs of the developing fetus, the subsequent course of pregnancy depends on the reliability of this stage. If the formation of the placenta is insufficient trophoblast infestation, then an inferior placenta will form - miscarriage or delayed development of the fetus; with inadequate construction of the placenta develops toxicosis of the second half of pregnancy; if the infestation is too deep, it is possible to increase the placenta, etc. The period of placentation and organogenesis is the most responsible in the development of pregnancy. Their correctness and reliability is ensured by a complex of changes in the mother's body.

At the end of the third and fourth months of pregnancy, along with the intensive growth of villi in the area of implantation, degeneration of the villi outside it begins. Not receiving adequate nutrition, they are subjected to pressure from the growing fetal sac, lose the epithelium and sclerosis, which is the stage of formation of a smooth chorion. The morphological feature of the formation of the placenta in this period is the appearance of a dark villous cytotrophoblast. Cells of dark cytotrophoblast have a high degree of functional activity. Another structural feature of the villi stroma is the approach of the capillaries to the epithelial cover, which makes it possible to accelerate the metabolism by reducing the epithelial-capillary distance. At the 16th week of pregnancy, there is an equalization of the placenta and fetal mass. In the future, the fetus quickly overtakes the mass of the placenta, and this trend remains until the end of pregnancy.

At the 5th month of pregnancy, a second wave of invasion of the cytotrophoblast occurs, which leads to an expansion of the lumen of the spiral arteries and an increase in the volume of uteroplacental blood flow.

At the 6th to 7th months of gestation, further development occurs in a more differentiated type, the high synthetic activity of syncytiotrophoblast, fibroblasts in the stroma of cells around the villi capillaries is maintained.

In the III trimester of pregnancy, the placenta does not significantly increase in mass, undergoes complex structural changes that allow to meet the growing needs of the fetus and its significant increase in weight.

At the 8th month of pregnancy, the greatest increase in placenta mass was noted. The complication of the structure of all components of the placenta, significant branching of the villi with the formation of cationidons was noted.

At the 9th month of pregnancy there was a slowdown in the rate of growth of the placenta mass, which is further intensified in 37-40 weeks. There is a clear lobed structure with a very powerful intervillar blood flow.

[7], [8], [9], [10]

Protein hormones of the placenta, decidual and membranes

During pregnancy, the placenta produces basic protein hormones, each of which corresponds to a certain pituitary or hypothalamic hormone and has similar biological and immunological properties.

Protein hormones of pregnancy

Protein hormones produced by the placenta

Hypothalamic-like hormones

• gonadotropin-releasing hormone
• corticotropin-releasing hormone
• thyrotropin-releasing hormone
• somatostatin

Pituitary-like hormones

• chorionic gonadotropin
• placental lactogen
• chorionic corticotropin
• adrenocorticotropic hormone

Growth Factors

• an insulin-like growth factor 1 (IGF-1)
• epidermal growth factor (EGF)
• platelet-derived growth factor (PGF)
• fibroblast growth factor (FGF)
• transforming growth factor P (TGFP)
• inhibin
• activin

Cytokines

• interleukin-1 (il-1)
• interleukin-6 (il-6)
• colony-stimulating factor 1 (CSF1)

Proteins specific for pregnancy

• beta1, α-glycoprotein (SP1)
• eosinophilic main protein pMBP
• soluble PP1-20 proteins
• membrane-binding proteins and enzymes

Protein hormones produced by the mother

Decidual proteins

• prolactin
• relaxin
• protein binding insulin-like growth factor 1 (IGFBP-1)
• interleukin 1
• colony-stimulating factor 1 (CSF-1)
• progesterone-associated-endometrial protein

Hypophyseal triple hormones correspond to chorionic gonadotropin (CH), chorionic somatomamotropin (CH), chorionic tyrotropin (XT), placental corticotropin (PCT). The placenta produces peptides similar to ACTH, as well as releasing hormones (gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), thyrotropin releasing hormone (TRH) and somatostatin) similar to hypatolactic hormones. It is believed that control of this important function of the placenta is carried out by HG and numerous growth factors.

Chorionic gonadotropin - the hormone of pregnancy, is a glycoprotein, similar in its effect to LH. Like all glycoproteins it consists of two chains of alpha and beta. The alpha subunit is almost identical with all glycoproteins, and the beta subunit is unique for each hormone. Chorionic gonadotropin is produced by syncytiotrophoblast. The gene responsible for the synthesis of the alpha subunit is located on the 6 chromosome, for the beta subunit of LH there is also one gene on 19 chromosomes, while for the beta subunit of CG there are 6 genes on 19 chromosomes. Perhaps this explains the uniqueness of the beta-subunit of HG, since its life span is approximately 24 hours, while the lifetime of beta-LH is not more than 2 hours.

Chorionic gonadotropin is the result of the interaction of sex steroids, cytokines, releasing hormone, growth factors, inhibin and activin. Chorionic gonadotropin appears on day 8 after ovulation, the day after implantation. The functions of the chorionic gonadotropin are extremely numerous: it supports the development and function of the yellow body of pregnancy until 7 weeks, takes part in the production of steroids in the fetus, the DEAC of the adrenal fetal zone and testosterone by the testicles of the male fetus, participating in the formation of the fetus sex. Expression of the chorionic gonadotropin gene in the fetal tissues: kidneys, adrenal glands, which indicates the participation of chorionic gonadotropin in the development of these organs. It is believed that it has immunosuppressive properties and is one of the main components of the "blocking properties of the serum", preventing the rejection of a foreign mother for the immune system of the fetus. Receptors for chorionic gonadotropin are found in myometrium and in vessels of myometrium, apparently, chorionic gonadotropin plays a role in the regulation of the uterus and vasodilation. In addition, the receptors for chorionic gonadotropin are expressed in the thyroid gland, and this explains the stimulating activity of the thyroid gland under the influence of the chorionic gonadotropin.

The maximum level of chorionic gonadotropin is observed at 8-10 weeks of pregnancy. 100,000 units then slowly decreases and is at 16 weeks 10,000-20,000 IU / I, remaining so until 34 weeks of gestation. At 34 weeks, many people mark the second peak of the chorionic gonadotropin, the significance of which is not clear.

Placental lactogen (sometimes called chorionic somato-mammothropine) has a biological and immunological similarity with the growth hormone, synthesized by syncytiotrophoblast. The synthesis of the hormone begins from the moment of implantation, and its level increases in parallel with the placenta, reaching a maximum level of 32 weeks of gestation. The daily production of this hormone at the end of pregnancy is more than 1 g.

According to Kaplan S. (1974), placental lactogen is the main metabolic hormone that provides the fetus with a nutrient substrate, the need for which increases with the growth of pregnancy. Placental lactogen is an insulin antagonist. An important source of energy for the fetus is the ketone body. Enhanced ketonogenesis is a consequence of a decrease in the effectiveness of insulin under the influence of placentral lactogen. In this regard, reduced utilization of glucose in the mother, which ensures a constant supply of fetal glucose. In addition, an increased level of insulin combined with a fused lactogen provides enhanced protein synthesis, stimulates the production of IGF-I. In the fetal blood of placenta lactogen there is little - 1-2% of the amount of it in the mother, but it can not be excluded that it directly affects the fetal metabolism.

"Chorionic Growth Hormone" or "growth hormone" variant is produced by syncytiotrophoblast, determined only in the mother's blood in the second trimester and increases to 36 weeks. It is believed that, like the placental lactogen, it takes part in the regulation of the IGFI level. Its biological effect is similar to that of placental lactogen.

In the placenta, a large number of peptide hormones are produced, very similar to the hormones of the pituitary and hypothalamus - chorionic tyrotropin, chorionic adrenocorticotropin, chorionic gonadotropin - releasing hormone. The role of these placental factors is not yet fully understood, they can act paracrine, providing the same effect as their hypothalamic and pituitary analogues.

In recent years, much attention has been paid to placental corticotropin-releasing hormone (CRH) in the literature. During pregnancy, CRH increases in plasma by the time of delivery. CRH in plasma is associated with CRH-binding protein, the level of which remains constant until the last weeks of pregnancy. Then its level drops sharply, and, in connection with this, the CRH increases significantly. Its physiological role is not entirely clear, but in the fetus CRH stimulates the level of ACTH and through it contributes to steroidogenesis. It is suggested that CRH plays a role in causing labor. Receptors for CRH are present in the myometrium, but the mechanism of action of CRH should not cause contraction, but the relaxation of the myometrium, since CRH increases cAMP (intracellular cyclic adenosine monophosphate). It is believed that in the myometrium the CRF receptor isoform or the binding protein phenotype changes, that through stimulation of the phospholipase may increase the level of intracellular calcium and thereby provoke the contractile activity of the myometrium.

In addition to protein hormones, the placenta produces a large number of growth factors and cytokines. These substances are necessary for the growth and development of the fetus and the immune relationship between the mother and the fetus, which ensure the preservation of pregnancy.

Interleukin-1beta is produced in decidua, colony-stimulating factor 1 (CSF-1) is produced in decidua and in the placenta. These factors are involved in fetal hematopoiesis. In the placenta, interleukin-6, tumor necrosis factor (TNF), interleukin-1 beta is produced. Interleukin-6, TNF stimulate the production of chorionic gonadotropin, insulin-like growth factors (IGF-I and IGF-II) are involved in the development of pregnancy. The study of the role of growth factors and cytokines opens a new era in the study of endocrine and immune relationships in pregnancy. A protein of insulin-like growth factor (IGFBP-1beta) is an important protein of pregnancy. IGF-1 is produced by the placenta and regulates the passage of nutrient substrates across the placenta to the fetus and, thus, provides growth and development of the fetus. IGFBP-1 is produced in decidua and binding IGF-1 inhibits fetal development and growth. The weight of the fetus, the rate of its development directly correlate with IGF-1 and back with lGFBP-1.

Epidermal growth factor (EGF) is synthesized in the trophoblast and is involved in the differentiation of the cytotrophoblast into syncytiotrophoblast. Other growth factors identified in the placenta include: nerve growth factor, fibroblasts, transforming growth factor, platelet growth factor. In the placenta, inhibin, activin is produced. Inhibin is defined in the syncytiotrophoblast, and its synthesis is stimulated by placental prostaglandins E, and F2 fla.

The action of placental inhibin and activin is similar to that of ovarian. They take part in the production of GnRH, HG and steroids: activin stimulates, and inhibin inhibits their production.

Placental and decidual activin and inhibin appear in the early stages of pregnancy and, apparently, take part in embryogenesis and local immune responses.

Among the proteins of pregnancy, the most known SP1 or beta1-glycoprotein or trophoblast specific beta1-glycoprotein (TBG), which was discovered by Tatarinov Yu.S. In 1971. This protein increases in pregnancy like placental lactogen and reflects the functional activity of trophoblast.

The eosinophilic main protein pMVR - its biological role is not clear, but by the analogy with the properties of this protein in eosinophils, a detoxifying and antimicrobial effect is assumed. A suggestion has been made with the effect of this protein on the contractility of the uterus.

Soluble placental proteins include a group of proteins with different molecular weight and biochemical composition of amino acids, but with common properties - they are in the placenta, in the placental-fruiting bloodstream but not secreted into the mother's blood. They are now open 30, and their role is basically reduced to providing transportation of substances to the fetus. The biological role of these proteins is being intensively studied.

In the system of mother-placenta-fetus, the maintenance of rheological properties of blood is of great importance. Despite the large contact surface and the slowing of the blood flow in the intervillous space, the blood is not thrombosed. This is hampered by a complex complex of coagulating and anticoagulant agents. The main role is played by thromboxane (TXA2, secreted by platelets of the mother - the activator of clotting of maternal blood, and also by the receptors to thrombin on the apical membranes of syncytiotrophoblast, which promote the transformation of maternal fibrinogen into fibrin.In contrast to the coagulating factors, an anticoagulant system, including annex V on the surface of the microvilli syncytiotrophoblast border of maternal blood and epithelium of villi, prostacyclin and some prostaglandins (PG12 and PGE2), which, in addition to vasodilatation, have an anti- a number of factors with antiplatelet properties have been identified, and their role remains to be studied.

Types of placenta

Edge attachment - the umbilical cord is attached to the placenta from the side. Shell attachment (1%) - the umbilical vessels, before attachment to the placenta, pass through the syncytio-capillary membranes. With the rupture of such vessels (as in the case of the vessels of the placenta), blood loss occurs from the fetal circulatory system. The additional placenta (placenta succenturia) (5%) represents additional lobules lying apart from the main placenta. In case of delay in the uterus of the additional lobule in the postpartum period, bleeding or sepsis may develop.

The placenta membranacea (1/3000) is a thin-walled sack that surrounds the fetus and thus occupies most of the uterine cavity. Located in the lower segment of the uterus, this placenta predisposes to bleeding in the prenatal period. It may not separate in the fetal period of childbirth. Increment of the placenta (placenta accreta) - abnormal increment of all or part of the placenta to the wall of the uterus.

Placenta presentation (placenta praevia)

The placenta lies in the lower segment of the uterus. Placenta previa is associated with conditions such as a large placenta (eg, twins); abnormalities of the uterus and fibroids; damage to the uterus (genera of many fruits, recent surgical intervention, including cesarean section). Beginning with a period of 18 weeks, ultrasound can visualize low-lying placentas; most of them move to the normal position at the onset of labor.

At type I the edge of the placenta does not reach the internal uterine throat; at type II, it reaches, but does not close inside the internal uterine yawn; In type III, the internal uterine ooze is closed from the inside by the placenta only when closed, but not with the uterine neck open. In type IV, the internal uterine pharynx is completely covered from the inside with the placenta. Clinical manifestation of the anomaly of the location of the placenta may be bleeding in the prenatal period (prenatal). Overgrowth of the placenta, when the overstretched lower segment is the source of bleeding, or the inability of the fetal head to insert (with a high location of the presenting part). The main problems in such cases are associated with bleeding and the way of delivery, as the placenta causes obstruction of the uterine orifice and can retire or become incremental during labor (in 5% of cases), especially after a caesarean section in the past (more than 24% of cases).

Tests to assess the function of the placenta

The placenta produces progesterone, human chorionic gonadotropin and human placental lactogen; only the last hormone can give information about the well-being of the placenta. If at the gestational age of more than 30 weeks with a re-determination of its concentration below 4 μg / ml, this suggests a violation of the placental function. The well-being of the fetus / placenta system is monitored by measuring the daily excretion of total estrogens or estriol in the urine or the determination of estriol in the blood plasma, since pregnenolone synthesized by the placenta is subsequently metabolized by the adrenal and fetal liver and then again by the placenta for the synthesis of estriol. The content of estradiol in urine and in plasma will be low if the mother suffers from severe liver damage or intrahepatic cholestasis or takes antibiotics; In the event of a malfunction in the mother of kidney function, a low level of estradiol in the urine and an elevated level in the blood will be observed.