Causes of labor

The causes of labor have not been sufficiently studied to date. We have listed the leading causes of labor.

The role of the central nervous system

The central nervous system plays a major role in preparing a woman's body for childbirth. With its help, all physiological processes occurring in the pregnant woman's body, including the process of childbirth, are directed and maintained at the appropriate level.

Particular attention should be paid to two physiological phenomena - the conditioned reflex and the dominant.

The dominant is a temporarily dominant reflex "physiological system" that directs the work of the nerve centers at a given moment. The dominant focus can be localized in the spinal cord, in the subcortical structures or in the cerebral cortex, therefore, according to the primary focus, a spinal dominant, subcortical or cortical dominant is distinguished.

The dominant is formed as a reflex physiological system necessarily with a primary focus in one of the sections of the central nervous system. The focus of persistent excitation in the CNS can be created not only by reflex, but also under the influence of hormones.

In obstetric practice, a number of scientists formulated the principle of the birth dominant. The presence of the gestational dominant contributes to the uncomplicated course of pregnancy and the bearing of the fetus. Changes associated with pregnancy and childbirth affect the entire body, so the concept of "birth dominant" unites both the higher nervous centers and the executive organs into a single dynamic system. Based on the changes occurring in the reproductive system, one can fairly accurately judge the formation of the so-called "peripheral link" of the birth dominant in women.

The main role in the onset and development of the birth act is played by internal impulses emanating from the fertilized egg and the pregnant uterus itself. In order for the uterus to be able to contract regularly, its "readiness" must be ensured, on the one hand, and the corresponding regulation from the central nervous system, on the other.

Based on the data presented, it can be concluded that the expression “biological readiness of a woman for childbirth” is essentially identical to the concept of “birth dominant”.

Psychological readiness of a woman for childbirth

Modern obstetricians attach great importance to the psychological state of a woman immediately before and during childbirth, since the physiological course of the birth act largely depends on it. In fact, the method of physiopsychoprophylactic preparation of a pregnant woman for childbirth, developed by domestic authors and recognized worldwide, is aimed at creating an optimally expressed psychological readiness for childbirth.

A number of works have proposed psychological aspects of therapeutic measures of the program of preparation of women for childbirth and in these cases due to the reduction of emotional stress there is an improvement in the condition of the fetus and faster adaptation of newborns in the first days of the child's life. We have studied the characteristics of the condition of newborns (neurological examination, electromyography, quantitative determination of muscle tone) in groups of pregnant women who underwent psychoprophylactic training and those who did not. At the same time, the condition of newborns was significantly better in the group of pregnant women who underwent psychoprophylactic training. The number of positive assessments of the condition of children on the Apgar scale increases, their clinical characteristics approach those in the group with a normal course of labor. The same can be said about the chronometric, tonometric and electromyographic characteristics. From this, a conclusion can be made about the powerful therapeutic effect of psychoprophylaxis on the condition of the fetus and the newborn. However, improvement in the motor sphere apparently occurs secondarily due to improved blood supply and decreased sensitivity to the hypoxic stressor during labor, since no changes in the functional structure of reflexes were detected when using psychoprophylactic preparation during the normal course of labor.

Changes in the state of consciousness associated with physiological childbirth

Unusual mental phenomena occurring during physiological childbirth are described. The most frequently reported subjective sensations were "the unusualness of one's own mental processes" (42.9% during childbirth and 48.9% after childbirth), unusually deep experiences of happiness or grief (39.8 and 48.9%, respectively), "almost telepathic contact with the child" (20.3 and 14.3%) or the same contact with relatives and husband (12 and 3%), panoramic experiences of life lived (11.3 and 3%), as well as the phenomenon of "disconnection" from what is happening and observation of oneself from the outside (6.8 and 5.3%).

In the postpartum period, 13.5% of patients reported unusual experiences related to sleep: difficulty falling asleep with the emergence of an uncontrollable flow of thoughts, “playing out” various life situations, previously absent colored dreams, difficulty waking up, nightmares, etc.

There are no analogues of the described phenomena in the literature, however, individual phenomena have been observed by various researchers in healthy people in unusual conditions of existence, for example, during sensory deprivation, intense and life-threatening work, work in a “hot” workshop, during natural disasters, as well as in some modern types of psychotherapy or in periterminal states.

Many authors, not without reason, believe that under such conditions healthy people develop changes in consciousness. We share this position, and by changes in consciousness we mean a variety of consciousness of a healthy person who is in unusual conditions of existence. In our observations, such conditions of existence were physiological childbirth.

Thus, almost half of the patients studied during physiological births experienced mental phenomena that were unusual for their usual everyday life.

The phenomena thus arise involuntarily (unconsciously) and are characterized by the patients themselves as unusual for them. However, women who have given birth for the first time, having experienced such experiences during their first birth, consider them "normal", common for childbirth, and willingly report them.

It is generally accepted that childbirth is a physiological act for which the mother's organism is evolutionarily prepared. However, at the same time, it is a process of forming perinatal matrices, i.e. stable functional structures that persist throughout life and are basic for many mental and physical reactions. The literature contains a lot of factual data that allow us to assert that the hypothesis of the formation of perinatal matrices has become an original theory.

The main perinatal matrices formed during labor correspond to the periods of labor:

• the first matrix is formed at the beginning of the first stage of labor;
• the second - when labor contractions intensify and the cervical os opens to 4-5 cm;
• the third - in the second stage of labor when the fetus passes through the birth canal;
• the fourth - at the moment of the child's birth.

It has been shown that the formed matrices are an integral part of human reactions in everyday life, but in some cases, for example, with significant neuropsychic stress, with a number of diseases, injuries, etc., they can be activated and fully or partially determine a person's reaction. Activation of matrices leads to strengthening of natural, evolutionarily developed and strengthened mechanisms of physiological protection and recovery. In particular, during the treatment of neuroses during psychotherapy sessions, altered states of consciousness occur, the phenomenology of which allows us to determine which matrix is activated and the activation of which matrix is most effective for therapy. Along with this, we believe that active waking consciousness prevents the inclusion of physiological mechanisms of recovery, and a change in consciousness is a physiological reaction that ensures its optimal level for the inclusion of the above-mentioned natural mechanisms of recovery.

Figuratively speaking, nature has taken care of the human psyche and under unusual conditions of its existence the level of consciousness in the psyche changes, causing unconscious forms of mental reactions, which, by analogy with the “archetypes” of K. G. Jung, can be called “archi-consciousness”.

What has been said about matrices applies to one part of the “mother-fetus” system – the fetus and the child being born, but it also applies to the other part – the mother.

The mother's body reacts to childbirth and the postpartum period with well-known mental and physical reactions, but above all with the activation of its own perinatal matrices and, in particular, a change in consciousness.

Thus, we tend to understand the mental phenomena described during physiological births as a manifestation of the activation of ancient mental mechanisms, as “arch-consciousness”.

Like any ancient mechanism of the psyche, "archi-consciousness" facilitates the activation of evolutionarily developed non-specific reserve mechanisms of health in general and recovery in particular. Such mechanisms are suppressed by active waking consciousness.

The role of the kallikrein-kinin system

The kallikrein-kinin system (KKS) is a multifunctional homeostatic system that, through the formation of quinines, is involved in the regulation of various functions, in particular, the reproductive system of the body. Kallikreins are serine proteases that release kinins from substrates present in plasma, called kininogens. Kallikreins are divided into two main types: plasmatic and glandular. There are also two main forms of kallikrein substrate - low-molecular-weight and high-molecular-weight kininogens present in plasma. Plasma kallikrein, also called Fletcher factor, releases kinins only from high-molecular-weight kininogen, also known as Fitzgerald factor. Plasma kallikrein is mainly in an inactive form (prekallikrein) and, together with high-molecular kininogen and the Hageman factor, is included in the blood coagulation mechanism, activating factor XI. This system also participates in the activation of plasminogen with its conversion to plasmin, as well as in the body's reactions to injury and inflammation.

The activity of the kallikrein-kinin system increases during normal pregnancy and is one of the important factors in the occurrence of contractile activity of the uterus during labor. It is also known that a number of disorders of pregnancy and labor are associated with the activation of the kallikrein-kinin system.

Suzuki, Matsuda (1992) studied the relationship between the kallikrein-kinin system and the blood coagulation systems in 37 women during pregnancy and labor. The most obvious changes were found in the function of the kallikrein-kinin system. The level of prekallikrein rapidly decreases from 196.8% in late pregnancy to 90.6% at the beginning of labor. This causes changes in the coagulating and fibrinolytic systems of the blood and affects the occurrence of uterine contractions with the onset of labor. The relationship between bradykinin receptors and the mechanism of labor onset is shown. Takeuchi (1986) studied bradykinin receptors in uterine muscle contractions. The receptors were studied in various tissues: in the pregnant uterus of rats, in the chorionic membrane and placenta of women. A specific receptor was found in the chorionic membrane of women and the uterus of rats. The receptor is located on the plasma membrane. The association constant and maximum binding capacity of the receptor were lowest in the uterus of rats on the 15th day of pregnancy, and increased during parturition.

In experiments on Wistar rats, kininogenase activity was detected in the uterus, placental vessels, amniotic fluid, and fetal membranes. Kallikrein-like enzymes were found in both active and, mainly, inactive forms. Lana et al. (1993) conclude that kallikrein-like enzymes may be directly involved in the processes of polypeptide hormones and indirectly, through the release of kinins, in the regulation of blood flow during pregnancy and labor.

According to N. V. Strizhova (1988), high activity of kininogenesis processes is important in the pathogenesis of hypoxic disorders of the fetus and newborn caused by late toxicosis of pregnancy, chronic inflammatory diseases of the mother, which determines the violation of the states of rheological properties of the blood, tone and permeability of blood vessels. As the severity of asphyxia deepens, there is a breakdown of adaptive mechanisms, including intense and unbalanced hyperactivation of kininogenesis. Clinical and experimental substantiation of the use of bradykinin inhibitor - parmidine in obstetric practice was carried out. The role of the kallikrein-kinin system in the occurrence of labor was established, and the use of parmidine is indicated in the treatment of disorders of the contractile function of the uterus during pregnancy and labor and improves the functional state of the fetus, reduces pain during labor. This is probably due to the fact that one of the reasons for the occurrence of anginal pain in stable angina is the hyperproduction of kinins and their irritation of the pain receptors of the heart.

The meaning of catecholamines

Catecholamines are represented in the animal organism by three derivatives, sequentially transforming into each other from DOPA into dopamine, then into norepinephrine and adrenaline. The adrenal glands store the main amount of adrenaline and norepinephrine.

Paraganglia are producers of norepinephrine (not adrenaline) and provide local supply of catecholamines to nearby organs and tissues.

The physiological effects of catecholamines are varied and affect almost all body systems.

Under the influence of sex hormones, the level of norepinephrine in the uterus changes. This distinguishes the adrenergic nerves of the genitals from other sympathetic neurons, with short neurons being more susceptible to the action of sex steroids than long ones. Thus, the introduction of estradiol leads to an increase in the content of norepinephrine in the uterus, vagina, and oviducts in different animal species. In humans, adrenaline and acetylcholine in the body and cervix of the uterus lead to increased contractions.

In the last days of pregnancy, only a small amount of norepinephrine can be detected in the uterus. A decrease in the uterine content of norepinephrine, according to a number of authors who conducted experiments on guinea pigs, rabbits, dogs, and humans, has the character of protection against fetoplacental ischemia during generalized sympathetic activation in the mother.

Changes in the content of catecholamines in the rat uterus at different stages of pregnancy, labor, and the postpartum period were revealed. A characteristic feature of adrenergic innervation is a decrease in fluorescence intensity, which indicates a decrease in the number of adrenergic fibers. In addition, we studied the contractile activity of the myometrium and the level of catecholamines in the blood during physiological and pathological labor. It was shown that adrenaline excites contractile activity of the non-pregnant uterus and inhibits spontaneous labor, while norepinephrine causes contractions of the pregnant uterus. It can be assumed that a decrease in the amount of adrenaline and an increase in the content of norepinephrine in the uterus is one of the mechanisms inducing the onset of labor. Thus, with weak labor, the content of adrenaline in the blood plasma did not differ significantly from that during normal labor, while the content of norepinephrine was almost 2 times less than in healthy women in labor. Thus, in case of uterine motor dysfunction with weak labor activity, a decrease in catecholamine concentration is revealed mainly due to norepinephrine. If we draw an analogy between the adrenaline:norepinephrine ratio in the myocardium, then the effects that are favorable for the heart are those that result in a decrease in the adrenaline concentration in the myocardium and a slight increase in the norepinephrine concentration. These shifts apparently reflect an increase in the organ's ability to adapt to high demands that arise not only during muscle work, but also in other situations. And, conversely, an increase in the adrenaline level in the myocardium and a decrease in the norepinephrine level indicate unfavorable changes in the functional state of the heart, a decrease in its adaptive capabilities, and also cause various disorders in its functioning. Therefore, the adrenaline:norepinephrine ratio in the myocardium is an important physiological constant. Zuspan et al. (1981) found that the uterine concentration of norepinephrine and adrenaline in hypertensive forms of toxicosis is higher than in normal pregnancy; this indicates an important role of catecholamines in the etiology and maintenance of hypertension. These data are confirmed by modern studies - in severe nephropathy, the content of norepinephrine in the myometrium of the uterine body and lower segment at the end of pregnancy and during labor is 30% higher than in uncomplicated pregnancy.

The role of endocrine factors

During pregnancy and childbirth, the function of all endocrine glands of a woman is restructured. Along with this, the growing activity of the endocrine glands of the growing fetus is also noted. A specific gland of pregnant women, the placenta, also plays a huge role.

The data of modern literature indicate that the most important role among the hormones participating in the change of hormonal relationships in the body of pregnant women belongs to estrogens, progesterone, corticosteroids and prostaglandins, which largely determine the characteristics of the course of pregnancy and childbirth. However, studies of recent years have shown that progesterone and estrogens play only an auxiliary role in the onset of childbirth. However, in sheep and goats, the lowest concentration of progesterone in the blood plasma is established before childbirth and the level of estrogens increases. Some authors have shown that the ratio of estradiol: progesterone in women increases before childbirth and this has a direct etiological relation to the onset of childbirth.

It has also been established that catechol estrogens, which are the main metabolites of estradiol, increase the formation of prostaglandins in the uterus even more than the original compound.

It has been shown that the content of catechol-estrogens in the blood of the umbilical artery and umbilical vein is higher in physiological labor than in elective cesarean section. At the same time, the role of catechol-estrogens in the synthesis of prostaglandins and in the potentiation of catecholamines through competitive inhibition of catechol-O-methyl-transferase is important, showing that catechol-estrogens can play an important role in triggering the onset of labor and delivery in humans. Catechol-estrogens also potentiate the lipolytic effect of adrenaline in the release of arachidonic acid from phospholipids. At the same time, no clear changes in the level of estradiol and progesterone in the peripheral blood before the onset of spontaneous labor have been revealed in humans. Previously, the content of steroid hormones and Ca ²⁺ ions in the blood serum of 5 groups of pregnant women and women in labor was studied: pregnant women at 38-39 weeks, women in labor at the beginning of labor, pregnant women with a normal and pathological preliminary period. To clarify the existing dependencies between steroid hormones, we conducted a correlation analysis. A correlation was found in the normal preliminary period between progesterone and estradiol. The correlation coefficient is 0.884, the probability is 99%. By the beginning of labor, the correlation dependence in this group is lost. In recent years, antigestagens have been increasingly used for the purpose of terminating pregnancy at early stages. Antigestagens sharply increase uterine contractility and therefore can be used for the purpose of inducing labor both separately and in combination with oxytocin.

The role of fetal adrenal hormones

The exact role of fetal adrenal hormones in the onset of labor has not been established, but they are also believed to have an auxiliary role. In the last decade, the role of fetal adrenal glands in post-term pregnancy and the onset of normal labor has been demonstrated. It has been experimentally established that in some animals, fetal adrenocortical activity increases in the last 10 days of pregnancy and reaches a maximum on the day of labor. In women who undergo cesarean section during full-term pregnancy but without labor, the concentration of corgisol in the umbilical cord blood is 3-4 times lower than in women during physiological labor. The level of corticosteroids in the umbilical artery reaches its maximum at 37 weeks of pregnancy, when the fetus reaches maturity. Cortisol and progesterone are antagonists both in blood plasma and in the uterus. Fetal cortisol has an inhibitory effect on progesterone and thereby stimulates the activity of the myometrium. In addition, cortisol increases the activity of estrogens and prostaglandin F2a in the placenta.

Many authors recognize the major role of the fetal adrenal glands in the development of labor. The maternal adrenal glands play a lesser role. The mechanism of action of cortisol is not limited to the "enzymatic" maturation of the fetus (for example, its lungs). Fetal corticosteroids penetrate the amniotic fluid, decidual membrane, occupy progesterone receptors, destroy lysosomes of cells and increase the synthesis of prostaglandins, which can lead to the onset of labor.

Increased synthesis of estrogens in the third trimester of pregnancy is naturally associated with increased synthesis of dehydroepiandrosterone by the fetal adrenal glands. In the placenta, estrogens are synthesized from the latter through a number of links, which increase the synthesis of actomyosin and increase the number of oxytocin receptors in the myometrium. An increase in the concentration of estrogens in the amniotic fluid is accompanied by an increase in the synthesis of prostaglandins.

The role of oxytocin

Oxytocin (OX) is produced in the magnocellular nuclei of the hypothalamus, descends along the axons of hypothalamic neurons and is stored in the posterior lobe of the pituitary gland.

As is known, the causes of labor remain insufficiently studied. Great importance is attached to the role of catecholamines and prostaglandins in the initiation of labor.

It is important to consider that the posterior lobe of the pituitary gland contains huge reserves of oxytocin, much larger than those needed to ensure normal physiological functions, and the synthesis of the peptide is not always directly related to the rate of its release. In this case, it is the newly synthesized hormone that is preferentially released.

Large stores of oxytocin in the pituitary gland may play an important role in emergency situations, such as during labor when the fetus is expelled or after blood loss.

However, it is quite difficult to determine the oxytocin content in blood plasma using the conventional radioimmunoassay method, and this approach does not provide the time resolution necessary to assess electrical phenomena that may last for only a few seconds.

At the same time, when studying the central regulation of oxytocin, we know nothing about how the bursts of electrical activity in oxytocin-producing cells are generated, or what determines the interval between successive periods of increased activity. Much is known about the neurotransmitters released along the neural pathways that are involved in stimulating or inhibiting the release of oxytocin. However, the neurotransmitters act in the immediate vicinity of the synapse, rather than circulating in the brain.

In this regard, the question of basal oxytocin release is important. It is believed that the physiological significance of basal plasma oxytocin levels and the changes that may occur with them has not been determined.

Oxytocin is one of the most powerful of all uterotropic agents. However, being a powerful activator of uterine contractions, its strength depends not only on the properties of oxytocin, but also on the physiological state of the uterus. Thus, the concentration threshold required to stimulate the estrogenized uterus of rats in vitro is 5-30 μU/ml, and for the human myometrium during full-term pregnancy 50-100 μU/ml. In molar concentrations, these levels correspond to 1-5 • 10 ¹¹ and 1-2 • 10 ¹⁰, respectively. Based on these data, it can be stated that at present there are no other oxytotic agents that achieve such a strength of action on the myometrium.

It is also important to note that the human uterus is even more sensitive during labor in vivo than in vitro; effective plasma oxytocin levels were doses of less than 10 μU/ml (< 2• 10 ¹⁰ M). Modern studies have also shown that the sensitivity of the human myometrium during labor is 1-4 μU/ml. In a comparative aspect, prostaglandin F 2a has only 1/3 of the oxytotic activity of the rat uterus in vitro. During full-term pregnancy in humans, the threshold dose of prostaglandin F 2a and prostaglandin E2 is approximately 3 orders of magnitude higher than that of oxytocin.

Maternal Oxytocin Levels: There has been much research on oxytocin levels during labor and delivery, and only a small number of studies on oxytocin levels during pregnancy.

Previously, attempts were made to determine oxytocin in biological environments of the human body using a biological method. However, these methods were obviously not very adequate, since they gave a large scatter of digital data on the content of oxytocin in biological environments of the human body. At present, new approaches to radioimmune determination of the concentration of oxytocin in biological environments have been developed. It has been established that uterine sensitivity clearly increases as pregnancy progresses, but oxytocin levels in the blood are simultaneously too low to stimulate uterine contractions.

With the development of radioimmune methods, series of studies based on large cohorts of pregnant women at different stages of pregnancy became possible.

In most studies, oxytocin is detected in blood plasma using the radioimmunoassay during pregnancy, and an increase in its concentration is noted as pregnancy progresses.

Oxytocin levels were also studied in different periods of labor using the radioimmune method. Most researchers noted the fact that during labor, oxytocin levels in the blood plasma are higher than during pregnancy. This increase is not very significant compared to the oxytocin level during pregnancy. Oxytocin levels in the first period of labor are slightly higher than oxytocin levels at the end of pregnancy. At the same time, they reached a maximum in the second and then decreased in the third period of labor. Oxytocin levels during spontaneous labor are significantly higher than during full-term pregnancy without labor. At the same time, no significant changes in oxytocin levels were found throughout the first period of labor. It can be assumed that oxytocin circulating in the mother's blood is oxytocin of pituitary origin, although immunoreactive oxytocin has been detected both in the human placenta and in the ovaries. At the same time, a number of studies have found that during labor in animals, there is a significant decrease in the level of oxytocin in the posterior pituitary gland. What happens in humans remains unknown.

Currently, two methods have been developed for determining oxytocin in blood plasma using two antisera to it. With intravenous administration of synthetic oxytocin in healthy women, a linear relationship was found between the dose of oxytocin administered and its level in blood plasma (1-2 mU/ml).

Fetal oxytocin levels. The first studies to determine oxytocin failed to detect oxytocin in maternal blood, while high levels were noted in fetal blood. At the same time, a distinct arteriovenous difference in its content in the umbilical cord vessels was revealed. Therefore, a number of authors believe that labor is caused by fetal rather than maternal oxytocin. It is also important to note that during pregnancy, oxytocinase regulates the oxytocin level in the blood, while oxytocinase activity was not detected in the fetal serum, which indicates that this enzyme does not pass into the fetal circulation. Many researchers have shown that oxytocin levels in the umbilical artery are higher than in the maternal venous blood. This gradient and the arteriovenous difference in the umbilical cord vessels give grounds to assume the passage of oxytocin through the placenta or rapid inactivation of oxytocin in the placenta. The placenta contains an aminopeptidase that can inactivate oxytocin (and vasopressin) and thus the fate of oxytocin extracted from the umbilical bloodstream is unknown. However, when oxytocin is injected into the maternal circulation to induce labor, the arteriovenous difference in oxytocin is reversed, suggesting that oxytocin transfer across the placenta is possible. Fetal-to-maternal oxytocin transfer has been demonstrated in experimental studies in baboons. An arteriovenous difference of 80 ng/ml is observed in spontaneous labor, and fetal blood flow across the placenta is 75 ml/min, resulting in oxytocin transfer to the mother of about 3 IU/ml, the amount of oxytocin sufficient to induce labor. Moreover, a high arteriovenous difference was found both in spontaneous labor and in cesarean section during labor. An increase in the level of oxytocin in the fetal blood was also noted in those women whose labor began earlier than the expected planned cesarean section, which indicates an increase in fetal oxytocin during the precursor period or in the latent phase of labor.

Autopsy of fetuses and newborns has shown that at 14-17 weeks of pregnancy the oxytocin content in the fetus is 10 ng, and in newborns - 544 ng. Thus, there is a 50-fold increase in the oxytocin content from the beginning of the second trimester until birth. If we assume that the oxytocin content in the pituitary gland at the beginning of labor is not less than 500 ng (equal to 250 IU), then this amount is sufficient for the transfer of 3.0 μU to the mother, which can cause the onset of labor. Immunoreactive oxytocin with full biological activity can be extracted from the human placenta after spontaneous physiological labor. This shows that the placenta does not destroy oxytocin as quickly as was previously believed, at least not during and after labor. This can possibly be explained by the fact that prostaglandins of the E1, E2 and F2a series, which are formed in the placenta mainly during childbirth, inhibit the activity of placental oxytocinase.

In fetal anencephaly, oxytocin is not produced in the hypothalamus and, except for significant secretion by the gonads, low levels of oxytocin can be expected in fetal plasma, although the possibility of diffusion of oxytocin from the mother cannot be excluded.

Amniotic fluid contains sufficient amounts of oxytocin to be detectable both during pregnancy and labor. Oxytocin in the amniotic fluid can reach the decidua and myometrium by diffusion through intracellular channels in the membrane. The fetus also secretes significant amounts of vasopressin. The arteriovenous difference in the umbilical cord vessels and the difference between maternal and fetal vasopressin are significantly greater than those of oxytocin. Although vasopressin has a lesser oxytotic effect than oxytocin on the pregnant female uterus, fetal vasopressin may enhance the effect of oxytocin. Secretion of vasopressin is stimulated by fetal distress and fetal vasopressin may therefore be of particular importance in the etiology of premature labor. However, little is known about the oxytotic effect of vasopressin on the human uterus at term.

Hypoxia stimulates the release of oxytocin in the fetus and, thus, stimulates uterine activity and accelerates labor in case of fetal distress. However, this hypothesis requires further research. In one of the modern works Thornton, Chariton, Murray et al. (1993) emphasized that although most authors recognize that the fetus produces oxytocin, a number of researchers do not believe that the fetus influences labor by releasing oxytocin. Thus, in anencephaly, the fetus does not produce oxytocin, although labor and the level of oxytocin in the mother were normal; the transition of fetal oxytocin into the maternal circulation is unlikely, since the placenta has high activity of cystine aminopeptidase, which actively destroys oxytocin; the progress of normal labor does not correlate with any measurable increase in oxytocin in the mother's blood plasma; No cystine aminopeptidase activity was detected in fetal plasma; maternal analgesia may influence fetal oxytocin release.

The fetus may stimulate the uterus by secreting oxytocin toward the placenta or by penetrating the myometrium via the amniotic fluid. This possibility requires further investigation, as reports of oxytocin concentrations in the amniotic fluid are contradictory. The decrease in fetal oxytocin formation was not associated with the use of pethidine (promedol) during labor. This is surprising, since oxytocin release from the posterior pituitary gland in animals is inhibited by endogenous opioid peptides or opiates and its effect is reversed by naloxone. However, fetal oxytocin formation was increased after epidural analgesia. In contrast to some studies, it has been shown that fetal oxytocin does not increase at the onset of labor after cesarean section, and this is convincing evidence, according to some authors, that fetal oxytocin does not affect uterine activity, and that fetal oxytocin secretion does not increase with the onset of labor or in the presence of fetal acidosis. These data require further research.

Thus, the following conclusion can be made about the role of oxytocin as the cause of labor:

• Oxytocin is the most powerful uterotropic agent during pregnancy and childbirth in humans;
• oxytocin is secreted by the mother and fetus in quantities that have physiological activity, provided that the myometrium reaches the high sensitivity to oxytocin necessary for the onset of labor;
• the sensitivity of the uterus to oxytocin is determined by the concentration of specific oxytocin receptors in the myometrium;
• the fetal neurohypophysis contains significant amounts of oxytocin;
• the concentration of oxytocin in the umbilical artery is higher than in the umbilical vein and maternal venous blood combined, indicating fetal secretion of oxytocin during labor and the disappearance of oxytocin from fetal blood plasma as it passes through the placenta;
• The decidua contains the same amounts of oxytocin as the myometrium.

The Importance of Prostaglandins

Prostaglandins (PG) in the uterus play an important role as a factor necessary for the maintenance and development of pregnancy at various stages. Currently, the phenomenon of antagonism between PGF2a and human chorionic gonadotropin (hCG) has been identified, which is the main mechanism for maintaining pregnancy. If this antagonism is disrupted, then a clear tendency to decrease human chorionic gonadotropin and increase the level of PGF2a begins to manifest itself, followed by the development of threatened and incipient termination of pregnancy. With the introduction of large doses of human chorionic gonadotropin in women with symptoms of threatened termination of pregnancy, it is possible to reduce the elevated level of PGF2a.

In recent years, reports have appeared that have expanded our knowledge of the preliminary link of prostaglandin synthesis and new hypotheses of the onset of labor have been proposed. In 1975, Gustavii proposed the following theory of the onset of labor: under the influence of changes in the level of estrogens and progesterone, changes occur in the decidual lysosomes, the enzyme phospholipase A2 is released, which acts on membrane phospholipids, releasing arachidonic acid and other precursors of PG. Under the action of prostaglandin synthetases, they are converted into PG, which cause uterine contractions. Uterine activity leads to decidual ischemia, which in turn stimulates further release of lysosomal enzymes, after which the cycle of PG synthesis enters a stable phase.

As labor progresses, there is a constant increase in the blood levels of PGF2a and PGE2, which confirms the position that an increase in intrauterine synthesis of PG is the cause of the appearance and strengthening of uterine contractions, leading to a successful completion of labor.

The most interesting and modern theory of the development of labor is the theory put forward by Lerat (1978). The author believes that the main factors in the development of labor are hormonal: maternal (oxytocin, PG), placental (estrogens and progesterone) and fetal hormones of the adrenal cortex and posterior pituitary gland. The hormones of the adrenal cortex change the metabolism of steroid hormones at the placenta level (reduced progesterone production and increased estrogen levels). These metabolic shifts, having a local effect, lead to the appearance of PG in the decidual membrane, the latter have a luteolytic effect, increase the release of oxytocin in the woman's pituitary gland and increase the tone of the uterus. The release of oxytocin by the fetus can cause the onset of labor, which then develops mainly under the influence of maternal oxytocin.

In a modern work by Khan, Ishihara, Sullivan, Elder (1992) it was shown that decidual cells, which were previously isolated from macrophages, after delivery form 30 times more PGE2 and PGF2a in culture than in cells before delivery. This increase in the level of prostaglandins in culture is noted for 72 hours and is associated with an increase in the number of cyclooxygenase cells from 5 to 95%. At the same time, no changes in the function of macrophages were detected. The presented data show that an increase in the level of PG from stromal cells is an important source of PG during delivery.

As is known, the importance of the E2 and F2 series of PGs in labor has been convincingly demonstrated by a number of researchers, but the body tissues that are the main source of these PGs in labor have not yet been identified. In particular, the formation of PG by the amnion has been studied, and changes in the content of PGE2 in the amnion during labor have been determined, but only in recent years has it been revealed that a very small amount of PGE2 is synthesized by the amnion and it passes through the chorionic decidua without its metabolism. Thus, the synthesis of PGE2 by the amnion at the beginning of labor is unlikely. A link between the synthesis of PG by the decidua and intrauterine infection has been proven. It is known that in full-term pregnancy, the decidua contains both types of cells - stromal cells and macrophages. The stromal cells of the decidua are the main source of PG in labor in humans (decidual macrophages make up 20%) of the decidua in full-term pregnancy. Most researchers have studied prostaglandin synthesis in the decidua without distinguishing between stromal cells and macrophages. However, further studies are needed to clarify the intracellular mechanisms of PG synthesis by decidual stromal cells. This confirms the position that an increase in intrauterine PG synthesis causes the appearance and strengthening of uterine contractions, leading to a favorable end of labor. It has also been shown that oxytocin is the cause of a significant increase in the production of PGE and PGF in the decidual tissue and myometrium of humans. Oxytocin from both the fetal and maternal organisms can be a source of increased PG synthesis. Oxytocin stimulates PG production in the pregnant uterus when the uterus is sensitive to oxytocin, and PG, in turn, increases the strength of oxytocin and causes contractions of the myometrium and dilation of the cervix.

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