The growth of long bones in human embryological and fetal upper limbs and its relationship to other developmental patterns

Measurements were made of the long bones of the upper limbs (humerus, ulna, radius) of 58 aborted embryos and fetuses, developmental age from 8 to 14 weeks, crown-rump length (CRL) between 38 and 116 mm. The specimens were cleared and double-stained, using alcian blue and alizarin red S for a differential detection of cartilage and bone. The values of both the total length (TL) and the ossified part (OL) of each long bone were related to the fetal developmental age previously estimated by freshly measured CRL. The relationship to another developmental pattern, i.e. the number of ossified centres in the vertebral column, suggested that the OL values could be much more significant than TL for the assessment of fetal growth.     

Cardiovascular malformations in spontaneously aborted human fetuses.

Among 57 spontaneously aborted fetuses with a crown-rump length (CRL) ranging from 30 to 180 mm, 5 were found to have cardiovascular malformations. The number of cases with cardiovascular malformations (numerator) and the number of observed fetuses (denominator) classified according to their CRL were as follows: CRL 30-49 mm, 1/9 (persistent left superior vena cava); 50-69 mm, 4/11 (one case each of membranous VSD with aberrant right subclavian artery, high muscular VSD, pulmonary stenosis with muscular VSD and overriding aorta, right aortic arch with membranous VSD); 70-99 mm, 0/7; 100-139 mm, 0/16; 140-180 mm, 0/14. The above results clearly show a high prevalence of cardiovascular malformations in spontaneously aborted fetuses with a CRL of less than 70 mm. The practicability and potential value of microdissection of small fetuses are stressed.     

Fetal development of the transverse atlantis and alar ligaments at the craniovertebral junction

Although the fetal development of the craniovertebral junction has long been of major interest to embryologists from the viewpoint of segmentation, development of the associated ligaments has received scant attention. Using semiserial horizontal sections from 18 embryos and fetuses (six embryos with a crown-rump length (CRL) of 20-26 mm or ~6-7 weeks of gestation; five fetuses with a CRL of 32-58 mm or 8-9 weeks; seven fetuses with a CRL of 90-115 mm or 14-15 weeks) without any abnormalities of cartilage configuration such as atlas assimilation, we studied the ligamentous structures along and around the odontoid process of the axis. The transverse atlantis and alar ligaments originated from a common mesenchymal condensation possibly corresponding to the proatlas segment: the former started to develop slightly earlier than the latter, and the morphologies of both were established at 7 weeks of gestation. Development of the joint cavitation around the odontoid process began in the mid-anterior area at 6 weeks, but was not fully completed even at 15 weeks (115 mm CRL). The presumptive joint cavity expressed vimentin and CD34 and contained abundant CD68-positive macrophages. We always found a mid-anterior joint cavitation facing the basi-occipital, but the embryological meaning remained unclear. The apical ligament appeared most likely to originate from the notochord sheath. The notochord was exposed from the tip of the odontoid process toward the loose epidural tissue and entered the occipital bone, but was difficult to trace to the anterior surface of the basi-occipital.     

Hand development in trisomy 21

The purpose of the present study was to evaluate hand size and maturity in fetuses with trisomy 21 (Down syndrome). Twenty-five fetuses, crown-rump length (CRL) 55–222 mm, foot length (FL) 8–42 mm, were included in the study. After whole-body radiography (Hewlett Packard Faxitron), special radiographs of the hand and foot were taken. Hand length was measured as the length of the third finger from the distal tip of the distal phalanx to the proximal tip of the metacarpal bone, the digital-metacarpal length (DML). The lengths of the proximal phalangeal bone (PPL) and the metacarpal bone (MCL) of the third finger were also measured. The DML, PPL, and MCL values of each fetus were related to CRL and FL. The individual hand bones were evaluated with regard to time of appearance on radiographs, sequence in comparison with the normal sequence of appearance, and morphology. The hand length is normal during the first half of the fetal period, whereas the length of individual bones in the third finger is reduced. The normal sequence of ossification, with the middle phalanx of the fifth finger last to ossify, also occurred in Down syndrome; however, this bone appeared later in Down syndrome. In four of the fetuses it did not appear (CRLs: 125, 158, 172, and 174 mm). Am. J. Med. Genet. 79:337–342, 1998. © 1998 Wiley-Liss, Inc.     

Vermiform Appendix During the Repackaging Process from Umbilical Herniation to Fixation onto the Right Posterior Abdomen

The anatomical position of the vermiform appendix varies among adults, and these variations are responsible for differences in the symptoms of appendicitis. However, to date no study has examined how and when these variations occur during fetal development. The present study examined horizontal sections of 27 midterm fetuses (crown rump length [CRL] 38–97 mm, gestational age approximately 8–15 weeks). There were 10 fetuses (CRL 56 mm or more) in which the cecum and appendix were in a posterosuperior site near the right kidney (postmigration phase), and 12 fetuses (CRL 39–72 mm) in which the ileocecal junction and appendix remained on the visceral surface of the liver in the anterior or anterolateral abdominal cavity (migration phase, after physiological umbilical herniation). Analysis of the 12 fetuses in the migration phase indicated that the appendix extended inferiorly in eight fetuses and superiorly in four fetuses. Likewise, a “preileal” appendix (a morphology in which the distal part of the appendix was in front of the terminal ileum) was present in eight of these fetuses. Extension of the appendix superiorly or inferiorly during the migration phase seems unrelated to the topographical relationship of the appendix with the terminal ileum at the postmigration phase in fetuses and in adults. Conversely, it seems likely that a retroileal appendix leads to a coiled appendix behind the ileocecal junction. “Guidance” by the liver surface seemed to be important for posterior migration, which ended with the ascent of the liver. Clin. Anat., 33:667–677, 2020. © 2019 Wiley Periodicals, Inc.     

Early fetal development of the human cerebellum

Early cerebellum development in humans is poorly understood. The present study histologically examined sections from 20 human embryos and fetuses at 6 weeks (12-16 mm crown-rump length (CRL); 4 specimens), 7-9 weeks (21-39 mm CRL; 8 specimens), 11-12 weeks (70-90 mm CRL; 4 specimens) and 15-16 weeks (110-130 mm CRL; 4 specimens). During 7-9 weeks (approximate CRL 28 mm), the rhombic lip (a pair of thickenings of the alar plate) protruded dorsally, bent laterally, extended ventrolaterally and fused with the medially located midbrain. During that process, the primitive choroid plexus appeared to become involved in the cerebellar hemisphere to form a centrally located eosinophilic matrix. At that stage, the inferior olive had already developed in the thick medulla. Thus, the term 'bulbo-pontine extension' may represent an erroneous labeling of a caudal part of the rhombic lip. The cerebellar vermis developed much later than the hemisphere possibly from a midline dark cell cluster near the aqueduct. In the midline area after 12 weeks (80 mm CRL), the growing bilateral hemispheres seem to provide mechanical stress such as rotation and shear that cause the development of several fissures much deeper than those on the hemisphere. The rapidly growing surface germinal layer may be a minor contributor to this vermian fissure formation. The vermian fissures seem to enable inside involvement of the surface germinal cells, and to induce cytodifferentiation of the vermis. Consequently, in the early stages, it appears that the cerebellar hemisphere and vermis develop independently of each other.     

Fetal loss in the first trimester after demonstration of cardiac activity: relation of cytogenetic and ultrasound findings

A retrospective comparison of cytogenetic and ultrasound findingsin first trimester spontaneous fetal loss after demonstrationof cardiac activity was made. The crownrump length (CRL) wasmeasured twice for each fetus resulting in spontaneous abortion:(i) CRL was measured in the viable state while demonstratingcardiac activity, and the growth deviation was expressed asthe measured/ expected CRL ratio (M/E CRL ratio); (ii) in thesame fetus, CRL was measured after confirmation of fetal death,and designated as the post-mortem CRL. The chorionic tissuesof these abortuses were karyotyped. The CRL of fetuses whichresulted in normal deliveries were also measured as controls.As a result, 16 of 24 abortuses displayed an abnormal chromosomalanalysis (67%). Themean M/E CRL ratio of still-viable fetuseswas smaller than that of control fetuses (0.74 ± 0.20versus 0.98 ± 0.13 respectively, P < 0.01). The differencesin ratio between karyotypically normal and abnormal abortuseswere not statistically significant. The post-mortem CRL of deadfetuses was >20 mm in four of five monosomy X, two of three21-trisomy, one of three triploidy and none of eight embryoswith normal karyotype and five other trisomies. In conclusion,our study demonstrated that the M/E CRL ratio could be usedas a predictor of spontaneous abortions, although it does notdiscriminate abnormal karyotypes from normal ones. The embryoswith a post-mortem CRL more than 20 mm have a higher likelihoodof suffering monosomy X or 21-trisomy. The ultrasonographicfindings might offer a cytogenetic clue as to a possible causeto the developmental arrest.     

黑质纹体系多巴胺神经元的发育与再生的关系

取不同头臀长(CRL)10～22mm(E13～18)鼠胚腹侧中脑制成悬液,分别移植至帕金森氏病模型鼠去多巴胺(DA)神经侧纹状体中。发现用CRL为10～16mm(E13～15)胚脑为供体的受移植鼠行为效应和移植区DA神经元存活情况远较以CRL为17～22mm供体为佳。用酪氨酸羟化酶(TH)免疫组化ABC法规察了不同胚龄(E_(13)～P_0)黑质纹体系DA神经元的形态和分布,发现CRL10～16mm(E13～15)时TH阳性细胞位于Sylvius导水管腹侧,此时DA细跑开始分化,至胚CRL17mm时TH阳性细胞已迁移至被益腹外侧,并大部分化出长突起,至出生时分化及迁移基本完成。本文讨论了DA神经元发育和其在受体脑内再生的关系。     

Effects of nutrient intake and sexual age of the dam at mating on fetal development in swine

Fifty-four Duroc gilts (mean wt = 88 kg, mean age = 164 d) were fed a 15% protein diet either ad libitum (F) or at a rate of approximately 50% of ad libitum daily (1.8 kg: L) prior to mating at either second (Exp. 1) or first (Exp. 2) observed estrus. Gilts were checked for estrus twice daily with a mature, active boar, mated at the appropriate estrus, and fed 1.8 kg of the prebreeding diet per gilt daily until slaughter between 42 and 49 days of gestation, mated gilts were slaughtered and measurements taken on fetuses and reproductive organs. In Exp. 1, fetal weight per day of gestational age (FetWDA), placental weight (PLW), crown-to-rump length (CRL) and uterine space per fetus (SP) were greater for fetuses from L gilts than F gilts (all P less than .05) with no difference in number of fetuses (P greater than .05). In Exp. 2, FetWDA was greater for fetuses from F gilts than L gilts (P less than .05), however there was no difference due to level of feeding for PLW, CRL and SP (all P greater than .10). Fetal weight (FW) was highly correlated with CRL indicated that a cubic relationship existed (both r = .97). In both studies, male fetuses grew more rapidly than female fetuses (P less than .05). These studies indicate that pre-breeding nutritional status and sexual age of the dam at conception have differential effects on fetal growth rate, but relationships among FW and CRL are not readily altered by pre-breeding level of feeding or sexual age of the dam at conception.(ABSTRACT TRUNCATED AT 250 WORDS)     

The distribution of fetal nuchal translucency thickness in normal Korean fetuses

The aim of present study was to establish normative data for the distribution of nuchal translucency (NT) thickness in normal Korean fetuses. The data were collected from pregnant women with singleton pregnancies in whom fetal ultrasound was performed and the fetal NT thickness was measured between 11 and 14 weeks of gestation. Among them, a total of 2,577 fetuses with a known normal outcome were included in this study. The distribution of multiple of median (MoM) values of the NT thickness with crown-rump length (CRL) in 10-mm intervals and the 95th percentile of MoM were calculated with the linear regression method. The present study showed that NT measurements increase with increasing CRL and a false positive rate increases with increasing gestational age. Therefore, a fixed cut-off point through the first trimester was not appropriate and each NT measurement should be examined according to the gestational age. The present study offers normative data of the fetal NT thickness in a Korean population, which can be used as reference for screening chromosomal aberrations or other congenital abnormalities in the first trimester.     

Morphogenesis of the Middle Ear during Fetal Development as Observed Via Magnetic Resonance Imaging

Recently, our research group has utilized serial histological sections to investigate the morphogenesis of the middle ear, which corresponds to the period of middle ear ossicle (MEO) cartilage formation. However, research regarding middle ear development during the post‐embryonic period has been limited. In the present study, we investigated morphogenesis of the middle ear in human fetuses with a crown‐rump length (CRL) between 37 and 197 mm using high‐resolution magnetic resonance imaging (MRI). Our findings indicated that the morphology of the MEOs is similar during fetal development and adulthood; further, growth of the MEOs nearly ceases once a CRL of 150 mm is attained. In each MEO, ossification spreads from a single center. The malleus and Meckel's cartilage could be discriminated in samples exhibiting a CRL of 145 mm based on differences in MRI signal intensity. In samples with a CRL of 86 mm, the tympanic cavity (TC) appeared as a thin yet distinct structure attached to the external auditory meatus at the convex surface. Only the handle of the malleus was covered by the TC, while the incus and stapes contacted the cavity at the region of articulation between the two ossicles only, even after a CRL of 145 mm had been attained. Thus, although the TC increased in both diameter and thickness, coverage did not extend across all three MEOs during the observation period. These data are expected to provide a useful standard for morphogenesis and may aid researchers in distinguishing between normal and abnormal development. Anat Rec, 301:757–764, 2018. © 2017 Wiley Periodicals Inc.     

The differentiation of white pulp and red pulp in the spleen of human fetuses (72–145 mm crown-rump length)

The development of the white and red pulp in spleen from thirteen human fetuses measuring from 72 mm to 145 mm in crown-rump length (CRL) was studied using the electron microscope. This period follows the development of the primary vascular reticulum (Weiss, '73). The white pulp appears first as a periarterial sheath with variable numbers of large and medium-sized lymphocytes, monocytes, macrophages, and some granulocytes and erythrocytes. It is always rich in macrophages. At 90 to 100 mm CRL, reticular cells closely associated with collagen and having a distinctive dark hyaloplasm appeared first in the endothelium and close about blood vessels and then out in the pulp. In the white pulp they became circumferentially arranged about the central artery while in the red pulp they formed a branching reticulum. Small lymphocytes were present in increasing number in the periarterial lymphatic sheath after the development of the circumferential reticulum. The venous sinuses developed and the marginal zone stood out as an erythrocyte-rich and macrophage-rich shell of reticulum surrounding the periarterial sheath.     

早孕期唇腭裂的超声诊断初探

目的探讨二维颜面部正交叉三切面联合扫查以及三维新技术在早孕期唇腭裂诊断中的应用价值。方法选取2018年6月至2019年7月于宁夏医科大学总医院接受早孕期产前超声筛查的胎儿599例,头臀径(CRL)50~84 mm。首先应用二维超声评估胎儿腭部的3个重要标志,即腭线(正中矢状切面)、上颌骨牙槽突(横切面)和鼻后三角底部(冠状切面)。然后适当放大可疑胎儿以及30例正常胎儿面部图像,采集正中矢状切面三维容积数据,应用TUI、OmniView等技术观察腭部,并给予脱机分析。所有胎儿均进行中孕期超声畸形筛查,并在产后或引产后给予追踪随访。结果本研究599例胎儿共发现7例不同类型的裂缺,其中单侧唇腭裂3例,双侧唇腭裂2例,中央型唇腭裂2例,其余胎儿3个超声标志均没有回声缺失或连续性中断,敏感度为87.5%,特异性为100%,假阳性率为0,假阴性率为12.5%。产前诊断结果均经产后或引产后证实。结论二维颜面部三切面联合扫查可用于筛查早孕期唇腭裂,三维容积数据分析有利于唇腭裂类型的精确诊断。     

Pregnancy outcome and infant follow-up of fetuses with abnormally increased first trimester nuchal translucency

The numbers of fetuses with an abnormal increased first trimester nuchal translucency (NT) but a confirmed normal anatomy and karyotyping is relatively small and therefore a challenge for prenatal counselling. The aim of the current study was to assess the long-term pregnancy outcome and infancy prognosis of 78 fetuses with NT > 95th centile of the normal range for crown-rump length (CRL). The most common abnormalities in this group were aneuploidy, which affected 32 of the fetuses followed by four and three cases which were miscarried or had cardiac defects respectively. The remaining euploid fetuses with normal detailed scans were followed throughout their infancy (mean 24 months; range 12-36 months). Post-natally, except for a correctable case of ventricular septal defect and a case of posterior urethral valve, no other abnormalities were detected. After excluding all aneuploid cases and using the maternal age as a second variable, an uncomplicated pregnancy outcome could be anticipated in 17 cases (100%) when the maternal age was <30 years and NT between 95th centile and 5 mm. However, the chance of a normal outcome dropped to 50% in four cases with maternal age > or =30 years and NT > or =5 mm (Fisher's exact test; P: = 0.02). These findings suggest that the long-term prognosis of the euploid fetuses with large NT (<5 mm) is reassuring in younger women.     

Lethal multiple pterygium syndrome: three consecutive cases in one family

We report on three sib fetuses with the lethal multiple pterygium syndrome (LMPS), one case occurring in a twin pregnancy. All three fetuses had a cystic hygroma and hydrops was detected by ultrasound. The classification scheme for LMPS proposed by Hall [1984] is examined. With our present state of knowledge of this syndrome, subdivision on bone-fusion types does not appear to be justified. Antenatal detection by ultrasound is possible in most pregnancies with a second affected fetus because of cystic hygroma and hydrops. In the term or near-term infant in which ultrasound has not shown cystic hygroma or hydrops, a diagnosis of Pena-Shokeir type I syndrome should be considered because pterygia are a component of that syndrome but cystic hygroma and hydrops are not.     

PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, congenital heart defects and distinctive facies. The disorder is genetically heterogeneous with approximately 50% of patients having PTPN11 mutations. Prenatally, the diagnosis of NS has been suspected following certain ultrasound findings, such as cystic hygroma, increased nuchal translucency (NT) and hydrops fetalis. Studies of fetuses with cystic hygroma have suggested an NS prevalence of 1–3%. A retrospective review was performed to assess the utility of PTPN11 testing based on prenatal sonographic findings ( n = 134). The most commonly reported indications for testing were increased NT and cystic hygroma. Analysis showed heterozygous missense mutations in 12 fetuses, corresponding to a positive test rate of 9%. PTPN11 mutations were identified in 16% and 2% of fetuses with cystic hygroma and increased NT, respectively. Among fetuses with isolated cystic hygroma, PTPN11 mutation prevalence was 11%. The mutations observed in the three fetuses with hydrops fetalis had previously been reported as somatic cancer mutations. Prenatal PTPN11 testing has diagnostic and possible prognostic properties that can aid in risk assessment and genetic counseling. As NS is genetically heterogeneous, negative PTPN11 testing cannot exclude the diagnosis and further study is warranted regarding the other NS genes.     

The fine structure of the placental labyrinth in the sloth,Bradypus tridactylus

The placental labyrinth of the three-toed sloth (Bradypus tridactylus) was examined by electron microscopy. The material available was from two fetuses of 55 mm and 150 mm crown-rump length (CRL). The placenta of the younger specimen was a transition form between the syndesmochorial type and the endotheliochorial type. The interhemal membrane of the 55 mm CRL specimen consisted of the following components: (1) hypertrophied maternal endothelial cells surrounding the maternal vessels; (2) a small amount of extracellular material and spindle-shaped cells, both presumed to be of maternal origin; (3) a layer of syncytial trophoblast that had an unusual, reticulated or sponge-like appearance; and (4) the fetal capillary endothelium. In addition, the fetal connective tissue contained hypertrophied mesenchymal cells that were characterized by abundant granular endoplasmic reticulum. The placenta of the 150 mm CRL fetus was poorly preserved, but it was possible to determine that the placenta was of the endotheliochorial type. There was a close apposition of maternal endothelium and trophoblast. The results confirmed virtually all of the light microscopic observations of Wislocki (1927; 1928b). The ultrastructure of the sloth interhemal membrane is compared to that of other endotheliochorial placentas, particularly that of the shrew, with which it shows many cytological similarities.     

Ontogenesis of the central serotonin neuron system of the rat--an immunohistochemical study

The peroxidase-antiperoxidase technique was used to study the ontogenesis of serotonin-containing neurons in fetal, neonatal and adult rats. Serotonin-containing neurons were first detected in a rat embryo of crown-rump length (CRL) 5 mm, bilaterally distributed in the ventral metencephalon near the isthmus rhombencephali. Serotonin fibers were first detected in CRL 6 mm embryos. There was a rapid increase in serotonin-immunoreactive neurons of embryos of 7-8 mm CRL. Serotonin neurons appeared initially as independent, bilateral groups of neurons, but as early as CRL 16 mm, the adult mid-line distribution was present, while the neurons that occurred as single groups in the adult already existed as single groups or at least were only partially connected across the mid-line. A continuous distribution of serotonin neurons was observed in the mesencephalic and pontine reticular formation from CRL 13 mm to the adult stage. It is suggested that the rapid increase in serotonin neurons at 7 and 8 mm CRL is associated with the completion of mitosis which occurs at this time.     

Effects of prenatal procarbazine administration on intrauterine development in rats.

The effects of prenatal procarbazine (PCZ) administration on the intrauterine development of rat fetuses were investigated. Gravid rats were treated on day 14 of gestation (GD14) with 25 mg or 50 mg/kg body weight PCZ via stomach tube. Controls received normal saline in the same dosis and manner. On GD20, all fetuses were collected by caesarian section. Live and dead fetuses as well as resorptions were counted. In the live fetuses, the following investigations were conducted: measurement of body weight, occipito-coccygeal-lenght (OCL), tail length (TL), placental weight and diameter, external macroscopic and binocular microscopic examination, and sectional analysis of the animals using the razorblade sectioning technique. Both PCZ doses caused a significant reduction in the number of live fetuses and a significant increase in resorptions. Mean body weight in PCZ groups was antidromic affected. OCL and TL were significantly depressed. Placental weight and diameter as well as number of dead fetuses were comparable to those of controls. External and sectional investigations revealed no PCZ-related deviations. In the light of our findings we conclude that PCZ in the doses used in this experimental study significantly affects the intrauterine development in rats in terms of fetal toxicity but displays no teratological properties.     

The development of the primary vascular reticulum in the spleen of human fetuses (38- to 57-mm crown-rump length)

The development of the primary vascular reticulum and of the capsule was studied electron microscopically in spleens from five human fetuses measuring 38, 42, 43, 50 and 57 mm in crown-rump length (CRL). The reticulum developed progressively. At 38 mm CRL reticular cells had short broad processes and the interstitium was quite limited. The reticulum continued to open with advancing age until, in the 57-mm fetus, reticular cells had long slender processes and formed a reticulum with voluminous interstices. Contiguous cells were attached by junctional complexes of the intermediate type (zonula adherens). The salient cytological features of reticular cells were vacuoles, ribosomes, and rough endoplasmic reticulum. An argyrophilic reticulum was present which, unlike the adult extracellular reticulum, was not closely associated with reticular cells and was composed, in certain sites, primarily of collagen. A rich vasculature of closed thin-walled loops was present in the 38-mm fetus. Thereafter, an open vascular pattern, most pronounced in the 50- and 57-mm CRL fetuses, was observed. Blood and macrophages lay in the interstices of the reticular meshwork and active vasculogenesis with marked differentiation into arteries, capillaries, veins, and vascular sinuses occurred. Endothelial cells were joined by junctional complexes of the intermediate type. The vessels lacked basal laminae or basement membranes. No evidence of significant hematopoiesis was observed. The capsule consisted of a simple layer of irregularly cuboidal cells having microvilli and cilia on the peritoneal surface, desmosomes and intermediate junctions on their lateral surfaces, cytoplasmic vacuoles, glycogen, fat, ribosomes, and rough endoplasmic reticulum, intercellular and infracellular spaces; the capsule rested on a well-defined basal lamina. Thus, a primary vascular reticulum developed and comprised the splenic pulp. Though of simple form, it accomplished the fundamental function of the spleen: a filter and modifier of blood.