Developmental relations between the weight of internal organs and somatic features of fetuses and newborns

The paper contains results of investigations on statistical developmental interrelations between the weight of brain, heart, lungs, liver, spleen, kidneys, adrenal glands and thymus, and the total length, the crown-rump length and the body weight, and the circumference of head, shoulders, chest and abdomen of fetuses and newborns in the age from 17 to 43 weeks of life. The character and the force of the relations between the degree of the development of the weight of organs and the body dimensions was investigated by statistical methods on three levels. On the basis of the value of linear correlation coefficients, statistical relations were determined between the weight of the particular organs and the particular sometic features. The dependence between the particular organs and the complex of somatic features was determined on the basis on the multiple regression analysis. On the other hand the relation between two complexes of features, i.e. all organs and all somatic features was investigated with the help of canonical correlation coefficients. The analysis of results indicated that between the weight of internal organs and the somatic features in the fetal period there exists a statistical developmental relation. The developmental relations are most strongly marked between the 6th and the 10th months of intrauterine life, while in the 5th month of life and in postmature fetuses and newborns they are weaker.     

Human brain gangliosides: developmental changes from early fetal stage to advanced age

The developmental profiles of the four major brain gangliosides, GM1, GD1a, GD1b, and GT1b, were examined in human frontal lobe covering the period from 10 fetal weeks to 80 years of age. The ganglioside concentration increased approx. 3-fold from the 10th gestational week to the age of about 5 years. Gangliosides GM1 and GD1a increased 12-15-fold during the same period. The most rapid increase of GM1 and GD1a occurred around term, during the period for dendrite arborization, outgrowth of axons and synaptogenesis. GT1b showed a quite different developmental curve. It was the major ganglioside during the 3rd to 5th gestational month, whereafter its concentration dropped rapidly to term, from which time the concentration then increased up to 50 years of age. Similar curves were found for the other gangliosides of the b-series, GD3, GD2, GD1b and GQ1b. Ganglioside 3'-isoLM1 was a characteristic early fetal ganglioside which dropped rapidly to the 5th gestational month, reached a small peak around term and then disappeared during adulthood. The concentration of gangliosides of the neolacto series was larger than that of the lacto series during the whole developmental period. In the beginning of the second trimester, 3'-LM1 constituted 2% and LD1 10% of total ganglioside sialic acid. The new findings demonstrate more dynamic changes of the ganglioside patterns during development than noted in previous studies.     

Adrenal glucocorticoid function and its regulation in human prenatal ontogeny and in the 1st week of life

A comparison of cortisol and ACTH level determination in 82 human fetal sera obtained in the 11th-34th week of the intrauterine development and 50 sera from infants 1-7 days of age has revealed several stages of pituitary-adrenal system (PAS) maturation. PAS is immature in the first trimester of embryogenesis when cortisol concentration in the human fetal blood is low. The functional relations between pituitary and adrenal glands begin to establish in the middle of prenatal developmental period. A prominent response to delivery stress indicates that by delivery PAS reaches a certain stage of maturation. The feedback between ACTH and cortisol secretions in the blood of infants 1-7 days of age demonstrates that the refractory period of PAS is absent in the neonates during the first week of their life.     

Changes in the weight of internal organs in the fetal ontogenesis

The purpose of this work was the investigation of the development of the weight of brain, heart, lungs, liver, spleen, kidneys, adrenal glands and thymus, and the developmental relations occurring between them in human fetuses and newborns. The material covering 1908 individuals of both sexes (632 fetuses and 1276 newborns) was collected in the Department of Pathological Anatomy in Poznań. During clinical autopsies the weight of organs was determined exactly to 0.1 g and the body weight exactly to 5 g. The age of the individuals was determined on the basis of the mean conception time (14-15 day after the beginning of the last menses) and it ranged from 17 to 43 weeks of gestation. The material was divided into 7 developmental periods. The first 6 periods cover the moon months successively from the 5th to the 10th and the last period covers the three final weeks (41-43). The problems were analysed on the basis of a comprehensive statistical analysis and the obtained results of the significant statistical dependences between the organs were confronted with the biological changes of the investigated features taking place in the period of fetal ontogenesis.     

Trace element content in the internal female genitalia of the fetus in the 2d half of pregnancy]

The dynamics of increasing the concentration of microelements in the ovary, uterine tubes, uterus and vagina in the second half of intrauterine life were studied. Changes in the concentration of microelements depend on increasing the weight of the organs in question beginning from the 4th up to the 10th month of the fetal period. Hence, copper, zinc, manganese, titanium, lead, molybdenum are necessary for development and formation of internal female genitalia.     

Labor market effects of intrauterine exposure to nutritional deficiency: Evidence from administrative data on Muslim immigrants in Denmark

This paper examines whether nutritional disruptions experienced during the stage of fetal development impair an individual's labor market productivity later in life. We consider intrauterine exposure to the month of Ramadan as a natural experiment that might cause shocks to the inflow of nutrients essential for fetal development. Specifically, we use administrative data from Denmark to investigate the impact of exposure to Ramadan in utero on labor market outcomes of adult Muslim males, including employment status, annual salary, hourly wage rate, and hours of work. Our findings indicate that potential exposure to nutritional disruptions during a critical stage of fetal development is likely to have scarring effects on the fetus expressed as poor labor market outcomes later in life. Specifically, exposure to Ramadan around the 7th month of gestation results in a lower likelihood of employment and, to a lesser extent, a lower salary, and reduced labor supply. For example, the 7th month intrauterine exposure to Ramadan is associated with a 2.6 percentage points reduction in the likelihood of employment among Muslim males. We do not find an impact on the wage rate. Finally, we also document suggestive evidence that these results may partially be driven by increased disability and to a lesser extent by poor educational attainment among those who were exposed to Ramadan during this particular period in utero.     

Nontrophoblastic placental tumors

The aim of the study was to investigate potential influence of placental tumors on fetal outcome. The study comprised 10 cases of placental tumors. The analysis included the sonographic assessment of the tumor, signs of fetal anemia, as well as signs of hemodynamic disturbances or heart failure, and intrauterine treatment. The fetal hemodynamic was examined on the basis of Doppler blood flow in the umbilical artery and vein, middle cerebral artery, and ductus venous. The evaluation of fetal heart included the measurement of heart size, blood flow through cardiac valves and the assessment of fetal heart function based on cardiovascular score. The fetal outcome was also assessed according to birthweight, gestational age at delivery, pH, Ap score at 5th minute, abnormal neurological development and the need of intrauterine therapy. Ten cases of placental tumors were prenatally detected from 1999 to 2011. Among them 7 cases of hypoechogenic, non-vascularized cysts were identified and these neither effected the hemodynamics nor complicated fetal outcome. The vascularized tumors (chorioangioma) were the cause of severe anemia and hemodynamic disturbances and these led to fetal cardiac heart failure. In all cases of vascularized tumors from 2-3 intrauterine transfusion were performed. Rich vascularized tumors (chorioangioma) may cause hemodynamic disturbances and fetal heart failure. This may require intrauterine treatment and may result in abnormal fetal outcome and neurological development.     

Haptoglobin study of sheep during the development process]

The development of haptoglobin blood system was studied in the sheeps during intrauterine development and early postnatal period. The haptoglobin content was shown to decrease with the foetus age, two peaks of its reliable increase having been, however, noted -- on the 55th and 105th days of development. After the birth the haptoglobin concentration in blood is relatively low, increases gradually and attains by the 8th month of life that in adult animals. In the blood serum of 45--120 days old foetuses two phenotypes of fetal haptoglobin were found; the adult haptoglobin is present only beginning from the 1st month of life.     

The involvement of proliferation and apoptosis in the early human gonad development

Distributions of the Ki-67, TP53, caspase-3 and AIFM1 markers were histologically investigated in the 5th to 9th week developing gonads of 12 human conceptuses using immunohistochemical and immunofluorescence methods. Between the 5th and 8th developmental week, proliferation gradually increased in the surface gonad epithelium (26–52 %) and stroma (19–42 %), but then slightly decreased in the surface epithelium (35 %) during the early foetal period. In medulla, low proliferation activity decreased from 15 to 12 % between the 7th and 9th week. At earliest stages of gonadal development, primordial germ cells (PGC) were only rarely TP53 positive. In the 7th and 8th week, almost all PGC-s displayed TP53 positivity, while their number decreased in early fetal period. During the investigated period, caspase-3 reactivity gradually decreased in surface epithelium, while it increased in PGC and medulla of developing gonad AIFM1-positivity first appeared in surface gonad epithelium and then predominantly in PCG-s while caspase-3 characterized different cell populations within the developing gonad. AIFM1 and caspase-3 co-localized only during the migration of PCG-s. The number and distribution of Ki-67, TP53, caspase-3 and AIFM1 reacting cells changed coincidently with development end regression of the sex cords in indifferent and early fetal gonad. Our results indicate that the number of PGC might be controlled by balance of TP53 and AIFM1, leading to caspase-3 independent cell death. Other cell populations are probably eliminated by caspase-3-dependent cell death. Both pathways of cell death seem to operate during early human gonad development, while their intensity varies depending on the cell type and developmental period analysed.     

Increase in regularity of fetal heart rate variability with age.

It is generally assumed that fetal heart rate variability increases with gestation, reflecting prenatal development of the autonomic nervous system. We examined standard measures quantifying fetal heart rate variability, as well as a complexity measure, approximate entropy, in 66 fetal magnetocardiograms recorded from 22 healthy pregnant women between the 16th and 42nd week of gestation. In particular, regularity in the fetal RR interval time series was assessed on the basis of symbolic dynamics. The results showed that, beside an overall increase in fetal heart rate variability and complexity during pregnancy, there was also an increase in specific sets of binary patterns with low approximate entropy, i.e., a high degree of regularity. These sets were characterized by short epochs of heart rate acceleration and deceleration, and comparison with surrogate data confirmed that their random occurrence is rare. The results most likely reflect the influence of increasingly differentiated fetal behavioral states and transitions between them in association with fetal development.     

Developmental changes in the expression of genes involved in cholesterol biosynthesis and lipid transport in human and rat fetal and neonatal livers

Cloned cDNAs encoding a number of enzymes involved in cholesterol biosynthesis as well as extracellular and intracellular lipid transport were used to compare the developmental maturation of these biologic functions in the fetal and neonatal rat and human liver. The results of RNA blot hybridization analyses indicate that steady-state levels of rat HMG-CoA synthase, HMG-CoA reductase and prenyl transferase mRNAs are highest in late fetal life and undergo precipitous (up to 80-fold) co-ordinate reductions immediately after parturition. These changes reflect the ability of the fetal rat liver to produce large quantities of cholesterol as well as the repression of this function during the suckling period in response to exogenous dietary cholesterol. Striking co-ordinate patterns of HMG-CoA synthase, reductase and prenyl-transferase mRNA accumulation were also observed in four extrahepatic rat tissues (brain, lung, intestine and kidney) during the perinatal period. The concentrations of all three mRNAs in the 8-week-old human fetal liver are similar to those observed throughout subsequent intrauterine development with less than 2-fold changes noted between the 8th through 25th weeks of gestation. Analysis of the levels of human apo AI, apo AII, apo B and liver fatty acid binding protein mRNAs during this period and in newborn liver specimens also indicated less than 2-3-fold changes. These observations suggest that the 8-week human liver has achieved a high degree of biochemical differentiation with respect to functions involved in lipid metabolism/transport which may be comparable to that present in 19-21 day fetal rat liver. Further analysis of human and rat fetal liver RNAs using cloned cDNAs should permit construction of a developmental time scale correlating hepatic biochemical differentiation to be constructed between these two mammalian species.     

Characterization of cytokeratin patterns in the developing human tongue.

The characterization of cytokeratin (CK) in adult oral mucosa and developing teeth have been well documented in human. Cytokeratin distribution in developing oral mucosa has not yet been described. The aim of this study was to identify the expression of CK in human fetal tongue (week 10 to week 23) and to correlate the results with morphological maturation. Simple epithelial CK are expressed in all cell layers during the early stages, essentially in peridermal cells. From the 14th week, CK 18 is present only in the taste buds, making this polypeptide a reliable marker for this sensory organ. CK 4 and 13 are expressed from the 10th to the 23rd week by both ventral and dorsal lingual epithelia. Terminal differentiation keratins (CK 1, 2 and 10-11) can only be detected immunohistochemically at the 14th week in some cells on the external surface of some papillae. The number of these papillae and positive cells increase at the 19th and 23rd weeks. The terminal differentiation markers are expressed several weeks earlier than the formation of a well-distinguished keratinized layer.     

Change of some quantitative indices of the proximal and the distal growth cartilage of the human tibia during the period of the prenatal osteogenesis

The zones of the tibial growth cartilage of human fetuses (6th lunar month), premature newborns (7th-8th lunar month) and mature newborns were micrometrically studied. The zone thickness, the chondrocyte number in a certain area and in the cell columns as well, and the volume density of the chondrocytes were determined. The obtained quantitative data show that the three indices undergo certain changes during the three age periods of the prenatal osteogenesis studied. They differ in the proximal and in the distal cartilages as well. The fetal tibia is found to be growing more intensively at its distal end. The quantitative processes within the growth cartilages of the tibia are more active during the earlier stages of the intrauterine period while the qualitative processes are found to be more active at the end of the intrauterine period.     

不同月龄大鼠空肠粘膜上皮细胞的形态、增殖及凋亡

为研究雄性大鼠空肠在发生、发育和衰老过程中上皮细胞增殖与凋亡形态学的变化,本实验采用增殖细胞核抗原(PCNA)免疫细胞化学染色、原位末端标记(TUNEL)法检测了不同生长发育阶段SD大鼠空肠绒毛粘膜上皮及小肠腺上皮的细胞增殖、凋亡的变化情况,并统计测量了不同发育阶段大鼠空肠绒毛的高度、肌层厚度及绒毛杯形细胞、肠腺杯形细胞的数量变化。观察到大鼠空肠肠腺隐窝增殖细胞的阳性着色表达从出生后开始增强,到3月龄时达最高峰,12月龄时增殖细胞阳性染色又减弱;凋亡细胞主要分布于固有层,凋亡阳性细胞数在3月龄最多;大鼠空肠绒毛的高度从初生后开始增加,到3月龄达顶峰,而后开始变矮;空肠肌层在3周龄、12月龄较厚;杯形细胞数量于生后3周迅速增长,不同发育阶段的大鼠空肠肠腺隐窝的杯形细胞数量与年龄呈正相关。     

Study of femoral torsion during prenatal growth: interpretations associated with the effects of intrauterine pressure

The developing fetus is protected from external environmental influences by maternal tissues. However, these structures have a limited elasticity, such that the fetus must grow in a confined space, constraining its size at the end of pregnancy. Can these constraints modify the morphology of the fetal skeleton? The intensity of these constraints increases between 5 months and birth, making it the most appropriate period to address this question. A sample of 89 fetal femora was analyzed, and results provide evidence that during this period, the torsion of the femoral shaft (quantified by means of a new three‐dimensional method) increases gradually. Two explanations were considered: this increase could signal effects of constraints induced by the intrauterine cavity, developmental patterning, or some combination of these two. Different arguments tend to support the biomechanical explanation, rather than a programming pattern formation. Indeed, the identification of the femur as a first degree lever, created by the hyperflexion of the fetal lower limbs on the pelvis, could explain the increase in femoral shaft torsion during prenatal life. A comparison with femora of infants is in accordance with this mechanical interpretation, which is possible through bone modeling/remodeling. Although genetic and epigenetic mechanisms may regulate timing of fetal development, our data suggest that at birth, the fetal skeleton also has an intrauterine mechanical history through adaptive bone plasticity. Am J Phys Anthropol, 2011. © 2011Wiley‐Liss, Inc.     

4-14C-progesterone conversion by the fetal rat adrenal gland in vitro.

The adrenal glands of rat fetuses with activated or inhibited pituitary adrenocorticotropic activity between the 15th and 22nd day of intrauterine development were incubated with 4-14C-progesterone for 3hr. Fetuses of intact mothers were used as controls. Conversion of progesterone into adrenal steroids was found increased on the 18th day of intrauterine development, i.e., at the time when fetal adrenocorticotropic activity begins. In comparison to controls, conversion of progesterone into fetal adrenal corticosteroids was the smallest in the fetuses of mothers with inhibited pituitary ACTH and the greatest in the adrenals of fetuses of mothers with activated pituitary adrenocorticotropic activity.     

Cx43基因在人类及小鼠胎心发育中的时空表达规律

目的　检测Cx4 3在人类和小鼠的胚胎心脏的表达 ,了解该基因在心脏发育过程中的表达规律。方法　选取人类 6～ 18孕周正常胚胎或胎儿心脏 6 3例 ,小鼠孕龄 9 5～ 16 5d胚胎心脏 6 4例 ,采用免疫组化法显示Cx4 3基因在心脏的表达。结果　早期人类胚胎心脏中 ,Cx4 3在心室肌中没有表达 ,心房肌表达微弱 ,原始小梁网中表达很高 ,随着胚胎发育 ,在心房和心室的表达逐渐增强 ,小梁网的表达在胚胎 13～ 14周达到高峰。室间隔的肌部表达量较弱 ,膜部室间隔不表达。房室瓣和大动脉根部管壁Cx4 3没有明显表达。除了在大动脉管壁表达不同 ,小鼠胚胎心脏表达规律与人类基本相同。结论　Cx4 3对于胚胎心脏的发育至关重要。     

Formation of extensor digitorum muscle proportions before and after birth

Studies on the formation of the extensor digitorum muscle morphological characteristics were carried out on material of 85 human fetuses (42 males and 43 females), 16 to 36 weeks old, and 45 adults (31 males and 14 females). Intermediary conclusions were drawn on probable changes occurring in the morphological formation of the muscle after birth, as a result of comparing proportions of the muscle at the fetal stage with its form in adults. In this work, the anthropometric method of study and statistical analysis of results have been applied. Analysis of the results in the fetal group has shown that all metrical characteristics of the muscle reach their maximum values at the end of the investigated ontogenetic space. This is, naturally, a consequence of evolution and growth of all fetal body measures, including elongation of forearms. However, the evolution of the individual muscle characteristics is not regular and though the direction of this growth is similar, its extent varies, and also differs slightly in sexual groups. Comparison of the values of muscle indices for 9 month old fetuses with the same indices for adults shows that relative dimensions of all investigated muscular characteristics decrease during the post-natal period except the relative length of the tendon.     

Standards of morphological development in fetuses and newborns as a method of defining fetal age

Whenever the calendar age of the studied fetal material is not known we are bound to reconstruct it by replacing it with the developmental age. In this paper some common developmental standards used in the determination of fetal age are reviewed. The standards, as found in the relevant literature, are tested against a control group for their accuracy in predicting fetal age. The results indicate considerable discrepancy among the various standards. Further, the developmental ages defined by these standards often differ considerably from the known menstrual age. My own attempt to present a more reliable set of developmental standards is based on the analysis of three morphological features commonly used in biological assessment. Body weight, crown-heel length, and crown-rump length are measured in weekly termed groups representing the 20th-42nd weeks of intrauterine life. The accuracy of body weight and crown-heel length in predicting fetal age is tested both within and against a control group. Statistical analysis show no significant differences between the predicted and known fetal ages. These results indicate that body weight and crown-heel length are reliable developmental standards from which fetal age can be defined.