The effect of unfavorable environmental factors on the mother-fetus system]

The paper provides a generalization of data and the results of own experiments with Wistar rats in the conditions of hypokinesia, immobilization, water deprivation, hypergravity, weightlessness and other factors affecting mother and fetus as a system. It gives a comparison of reactivity of pregnant and non-pregnant animals under stress, and also of the effects of unfavorable impacts sustained during various phases of ontogenesis: in pubertation period, directly before pregnancy and during various phases of pregnancy. It demonstrated that exposition of pregnant animals to unfavorable conditions is accompanied by significant stress of the compensatory-adaptive possibilities of mother aiming to support of homeostasis of the developing fetus. Clear changes develop in fetus only in case the adaptive possibilities of mother turn out inadequate or when the developing organs of fetus become active components of adaptive reaction of mother-fetus system and compensate for functional inadequacy of some mother's organ. The paper discusses the problem of individual features of resistivity and reactivity.     

Pregnancy and viral infections: Mechanisms of fetal damage,diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1–2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy.Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes.The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal?neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.     

Effect of maternal tobacco smoking or exposure to second-hand smoke on the levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of mother and the first urine of newborn

Tobacco smoking during pregnancy is associated with a variety of negative consequences not only for the mother, but also for the developing fetus. Many studies have shown that carcinogens contained in tobacco smoke permeate across the placenta, and are found in fetus. The aim of the study was to determine the prenatal exposure to tobacco-specific carcinogenic N-nitrosamines on the basis of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of smoking and second-hand smoke (SHS) exposed women and in the first urine of their newborns. A questionnaire documenting demographics and socio-economical data, smoking habits and exposure to SHS was completed by 121 delivering women near or at term. Maternal concentrations of cotinine and NNAL were measured in urine of the mother and the first urine of her newborn infant by liquid chromatography tandem mass spectrometry (LC/MS/MS). The mean concentration of cotinine was 439.2 ng/mg creatinine and NNAL concentration in urine of smoking women was 74.0 pg/mg creatinine, and for her newborn 78.6 pg/mg creatinine. Among mothers exposed to SHS, cotinine and NNAL mean concentration were 23.1 ng/mg creatinine, and 26.4 pg/mg creatinine. In newborns of SHS exposed mothers during pregnancy the mean concentration of NNAL was 34.1 pg/mg creatinine, respectively. Active tobacco smoking as well as passive exposure to smoking during pregnancy is an important source of tobacco specific N-nitrosamines to the fetuses as evidenced by increased concentrations of this carcinogen. Determination of NNAL in maternal urine samples can be a useful biomarker of prenatal exposure of newborn to carcinogenic nitrosamines.     

Maternal glucocorticoid hormones as a factor mediating the effect of prenatal stress on offspring anxiety

The plus-maze behavior was studied in offsprings of female rats subjected to immobilization stress on the 15-18 days of pregnancy. Prenatal stress decreased the level of anxiety in males and increased in females. The blockade of the mother's stress-induced glucocorticoid secretion by prior adrenalectomy and subsequent corticosterone injection during immobilization in a low dose (0.3 mg/kg) prevented the behavioral disorders in offsprings. In case of a higher dose of corticosterone (3 mg/kg) injection, the behavior of offsprings was the same as that of offsprings of the intact mothers subjected to immobilization. The results suggest that the stress-induced increase in maternal glucocorticoid level may be the mechanism by which prenatal stress impairs the development of sex differences in rat anxiety behavior.     

妊娠期糖代谢异常对新生儿出生结局的影响

目的：探讨妊娠期不同程度的糖代谢异常对胎儿发育及结局的影响。方法：前瞻性收集我院2009年1月至2010年1月分娩的糖代谢异常的331例单胎妊娠孕妇,分为糖筛查异常组69例、糖耐量异常组126例、妊娠期糖尿病（Gestaional DiabetesMellitus,GDM）组136例,并选择同期糖代谢正常的751例单胎孕妇为对照组,比较四组新生儿出生的最终结局。结果：糖筛查异常组与对照组新生儿结局差异无显著性意义（P〉0.05）;糖耐量异常组中巨大儿及新生儿窒息、早产儿的发生率与对照组差异有显著性意义（P〈0.05）;GDM组与对照组差异有显著性意义（P〈0.05）。结论：母亲妊娠期不同程度的糖代谢异常对新生儿影响不同。口服葡萄糖耐量试验（Oral Glucose Tolerance Test,OGTT）异常与GDM一样对新生儿发育及结局均有影响,可使巨大儿、新生儿窒息、早产儿的发生率增高。     

妊娠期糖代谢异常对新生儿出生结局的影响

目的:探讨妊娠期不同程度的糖代谢异常对胎儿发育及结局的影响。方法:前瞻性收集我院2009年1月至2010年1月分娩的糖代谢异常的331例单胎妊娠孕妇,分为糖筛查异常组69例、糖耐量异常组126例、妊娠期糖尿病(Gestaional DiabetesMellitus,GDM)组136例,并选择同期糖代谢正常的751例单胎孕妇为对照组,比较四组新生儿出生的最终结局。结果:糖筛查异常组与对照组新生儿结局差异无显著性意义(P>0.05);糖耐量异常组中巨大儿及新生儿窒息、早产儿的发生率与对照组差异有显著性意义(P<0.05);GDM组与对照组差异有显著性意义(P<0.05)。结论:母亲妊娠期不同程度的糖代谢异常对新生儿影响不同。口服葡萄糖耐量试验(Oral Glucose Tolerance Test,OGTT)异常与GDM一样对新生儿发育及结局均有影响,可使巨大儿、新生儿窒息、早产儿的发生率增高。     

Identifying a window of vulnerability during fetal development in a maternal iron restriction model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring.Our data may have significant relevance for understanding the impact of suboptimal iron levels during pregnancy not only on the mother but also on the developing fetus and hence might lead to a more informed timing of iron supplementation during pregnancy.     

Effect of prenatal stress on the hormonal response to acute and chronic stress and on immune parameters in the offspring

The effect of prenatal stress on the time course of the corticosterone response to acute and chronic stress and on hematological and immunological parameters in the offspring were analized in the present study. Pregnant Sprague-Dawley rats were stressed daily for 2 hours during the last week of gestation, and female and male off-spring were studied during adulthood. Corticosterone response to acute immobilization stress was not significantly different in either control or prenatally stressed rats. However, after 10 days of immobilization stress the corticosterone response completely disappeared in the control animals but not in the prenatally stressed group: high levels of corticosterone were found during the first hour of stress, although they were lower than those found in acutely stressed rats. Adrenal hypertrophy in response to prenatal stress was observed in females but not in male offspring, and chronic stress only increased adrenal weights in the male control group. Prenatal stress decreased the total peripheral leukocyte count, altered its diferential count decreasing lymphocytes and increasing neutrophil and eosinhophil counts, and significantly reduced the percentage of peripheral lymphocyte T CD8+ subset in male offspring. Chronic stress also reduced the percentage of the peripheral T CD8+ lymphocyte subset in the control group but not in the prenatally stressed group. These results suggest that the exposure to stress during pregnancy alters the adaptative response of the hypothalamus-pituitary-adrenocortical axis to chronic stress and presumably the immune competence in the offspring.     

Influence of psychosomatic stress in pregnant guinea-pigs on fetal lipid metabolism

After a psychosomatic stress applied to pregnant guinea-pigs, 7 or 1 day before term, plasma cortisol and non-esterified fatty acid levels increased immediately in mother and fetus. Plasma levels of cortisol and non-esterified fatty acids in newborns of mothers stressed 1 day before term were lower than in newborns of control mothers. The prenatal stress changed composition of triacylglycerol and phospholipids in newborn liver by inhibiting the postnatal increase of triacylglycerol and phospholipid stearic acid and by inhibiting the postnatal decrease in phospholipid palmitic, palmitoleic, linolenic and arachidonic acids.     

Passive smoking in utero: its effects on neonatal appearance.

Smoking causes changes in the appearance of adults and has profound effects on the fetus, but little is known about its effects on the appearance of newborn infants. Two colour photographs (face and whole body) of 15 newborn infants (seven born to mothers who had smoked during pregnancy and eight born to mothers who had not) were shown to 100 medical and nursing staff, who in a double blind trial were asked to identify which babies had been born to smokers. The mean number correctly identified was 9.1, which was significant compared with the number expected by random selection (7.5). No specific features were identified that distinguished the two groups of infants; selection was intuitive. Nevertheless, the fact that differences can be detected in some way may be useful for antismoking health education.     

The concentration of selected elements in the placenta according to selected sociodemographic factors and their effect on birth mass and birth length of newborns

Background and aimsThe placenta is a remarkable organ which provides critical transport functions between the maternal and fetal circulations during pregnancy. The demand for mineral components increases during the gestational period, therefore, an appropriate intake of minerals, such as calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese, determines the correct growth and development of a fetus. The aim of the study was to assess the concentration of selected elements in the placenta, and to assess the impact of their concentrations on the birth weight and birth length of newborns. The second aim of the study was to assess the influence of selected sociodemographic factors on the concentration of elements in the placenta.ResultsThe study demonstrated that the age of mothers affected the concentration of Ca and Mn in the placenta, and their habit of tobacco smoking during the gestational period was associated with higher concentrations of Ca, P, K, Mg, Fe, Cu, and Cd in the placental tissue. The results also showed that concentrations of K, Fe, Zn, and Mn in the placental tissue affected birth length. Furthermore, the association was demonstrated between a higher Cd concentration in the placenta (≥ 0.0503 μg/g) and the birth anthropometric parameters of neonates.ConclusionsSmoking during pregnancy and environment pollution are the factors that affects the concentration of elements in the placenta and contributes to their high accumulation in the placenta. Smoking during pregnancy causes an increased concentration of cadmium in the placenta which has negative health effects for the newborn. Women living in a big city or village had a higher concentration of cadmium in their placentas compared to women living in smaller cities. The significant influence of some elements (K, Fe, Zn, Cu and Cd) on the newborn’s birth parameters was also demonstrated. The results of our research indicate the importance of the mother’s lifestyle in providing the placenta with elements, which affects the growth of the fetus.

• •The placenta is an organ that is responsible for the proper course of pregnancy and fetal development.
• •The demand for mineral components increases during the gestational period, therefore, an appropriate intake of minerals determines the correct growth and development of a fetus
• •Increased exposure to arsenic, cadmium and lead during the gestational period can induce miscarriage, premature delivery, risk of fetal death, inhibition of intrauterine growth and development of the fetus, and low birth parameters.

     

Metabolic Profiles in Ovine Carotid Arteries with Developmental Maturation and Long-Term Hypoxia

Background

Long-term hypoxia (LTH) is an important stressor related to health and disease during development. At different time points from fetus to adult, we are exposed to hypoxic stress because of placental insufficiency, high-altitude residence, smoking, chronic anemia, pulmonary, and heart disorders, as well as cancers. Intrauterine hypoxia can lead to fetal growth restriction and long-term sequelae such as cognitive impairments, hypertension, cardiovascular disorders, diabetes, and schizophrenia. Similarly, prolonged hypoxic exposure during adult life can lead to acute mountain sickness, chronic fatigue, chronic headache, cognitive impairment, acute cerebral and/or pulmonary edema, and death.

Aim

LTH also can lead to alteration in metabolites such as fumarate, 2-oxoglutarate, malate, and lactate, which are linked to epigenetic regulation of gene expression. Importantly, during the intrauterine life, a fetus is under a relative hypoxic environment, as compared to newborn or adult. Thus, the changes in gene expression with development from fetus to newborn to adult may be as a consequence of underlying changes in the metabolic profile because of the hypoxic environment along with developmental maturation. To examine this possibility, we examined the metabolic profile in carotid arteries from near-term fetus, newborn, and adult sheep in both normoxic and long-term hypoxic acclimatized groups.

Results

Our results demonstrate that LTH differentially regulated glucose metabolism, mitochondrial metabolism, nicotinamide cofactor metabolism, oxidative stress and antioxidants, membrane lipid hydrolysis, and free fatty acid metabolism, each of which may play a role in genetic-epigenetic regulation.     

Amniogenic band anomalies in a fifth-month fetus and in a newborn from maternal oophorectomy during early pregnancy

A fifth-month fetus and a newborn with amniogenic band anomalies were examined at autopsy. Both specimens were obtained from women who had undergone oophorectomy during early pregnancy. The dead male fetus was aborted spontaneously, and had a micrognathia, a right club foot, and a constriction ring on the left lower leg. The left fingers 2, 3, and 4 were attached to the placenta by a fibrous string. No internal anomaly was noted. In the other case, a male newborn was delivered at the 39th week of gestation and had an agenesis of the calvarium, a cleft lip with palate, an amputation of the right toe, and constriction rings on right fingers 3 and 4 and left finger 3. The placenta was attached to the left temporooccipital region of the head by a fibrous string. Also present was an atrial septum defect and a horseshoe kidney. Possible etiology is discussed in relation to the "amniogenic bands" hypotheses.     

Vulnerability of placental antibody transfer and fetal complement synthesis to disturbance of the pregnant monkey

Maternal and fetal/infant antibody levels were assessed across pregnancy and at birth to evaluate the prenatal transmission of IgG in the rhesus monkey. Although some antibody was evident in the fetus by midpregnancy, the marked increase in IgG occurred primarily during the last two weeks of pregnancy. This delay until the end of pregnancy would result in low antibody titers in premature infants. In contrast, when gestation length was normal, the placental transfer of IgG was resistant to both dexamethasone treatment and a prolonged period of stress during pregnancy. This resiliency occurred despite an effect of prenatal stress on other aspects of infant development, including physical growth and the fetal synthesis of complement proteins.     

Issues in newborn screening

Newborn screening aims at the earliest possible recognition of disorders so that intervention with effective treatment can prevent the most serious consequences of the disorder. However, of several thousand known genetic disorders, therapy is presently available for only a small proportion of them. Newborn screening was first applied to phenylketonuria (PKU). Presently, newborn screening programs have been implemented in 26 countries for different diseases. However, potential problems in newborn screening programs that make implementation of newborn screening programs difficult include quality assessment, concerns about professional and technical competence, and ethical considerations. It has been shown that in the process from sampling the newborn to reporting of the screening results most errors are made in the pre- and post-analytical phases. It appears that much more could be done for the fetus if genetic screening and diagnostics could be accomplished early in pregnancy rather than after birth.     

The evolution of alpha-1 and alpha-2-macroglobulin levels in the serum of rabbit fetus and newborn

The study of the evolution of alpha-1 and alpha-2-macroglobulin levels in the rabbit fetus and newborn reveals an analogy between alpha-1-macroglobulin in the rabbit and alpha-2-macroglobulin in humans.     

Influence of surgical pain stress on the blood-brain barrier permeability in rats

Effect of surgical pain stress on the blood-brain barrier permeability was investigated in rats. The animals were divided into four groups: Group 1: control, Group 2: immobilization stress, Group 3: acute hypertension, Group 4: immobilization stress + surgical pain stress.Bilateral hid paw surgical wounds for cannulations were applied in animals' inguinal regions under diethyl-ether anesthesia, then the animals were awaken from anesthesia to produce surgical pain stress. Evans-blue was used as a blood-brain barrier tracer. There is no significantly blood-brain barrier breakdown after short-time immobilization stress, but after adrenalin hypertension blood-brain barrier permeability was increased especially on frontal and occipital cortices in 50% of the animals. Surgical pain stress increased blood-brain barrier permeabiliy in comparison to acute adrenalin-induced hypertension (p < 0.01). In surgical pain stress-induced animals distinct Evans-blue leakage was observed in the occipital, frontal and parieto-temporal cortices.     

In utero immobilization stress and its effects on the development, behavior and sexual maturity of the rat

The effect of prenatal stress from psychophysical immobilization, the applied during gestation, has been studied as well as its consequences on the development, behavior and sexual maturity in the offspring. Modifications in development were slight, even when intensified at four months of age. Whereas male sexual behavior showed only slight variation, female sexual maturity was markedly changed in experimental animals as compared to controls. From the present results, the psychopathological action from immobilization stress in utero on offspring is questionable.     

Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS) may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.