Prenatal Fetuses Research Articles

Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: a Chinese cohort study

BackgroundThe contribution of genetic variants to congenital heart defects (CHDs) has been investigated in many postnatal cohorts but described in few prenatal fetus cohorts. Overall, specific genetic variants especially copy number variants (CNVs) leading to CHDs are somewhat diverse among different prenatal cohort studies. In this study, a total of 1118 fetuses with confirmed CHDs were recruited from three units over a 5-year period, composing 961 of singleton pregnancies and 157 of twin pregnancies. We performed chromosomal microarray analysis on all cases to detect numerical chromosomal abnormalities (NCAs) and pathogenic/likely pathogenic CNVs (P/LP CNVs) and employed whole-exome sequencing for some cases without NCAs and P/LP CNVs to detect P/LP sequence variants (P/LP SVs).ResultsOverall, NCAs and P/LP CNVs were identified in 17.6% (197/1118) of cases, with NCA accounting for 9.1% (102/1118) and P/LP CNV for 8.5% (95/1118). Nonisolated CHDs showed a significantly higher frequency of NCA than isolated CHD (27.3% vs. 4.4%, p < 0.001), but there was no significant difference in the frequency of P/LP CNVs between isolated and nonisolated CHD (11.7% vs. 7.7%). A total of 109 P/LP CNVs were identified in 95 fetuses, consisting of 97 (89.0%) de novo, 6 (5.5%) parental inherited and 6 (5.5%) with unavailable parental information. The 16p11.2 proximal BP4-BP5 deletion was detected in 0.9% (10/1118) of all cases, second only to the most common 22q11.21 proximal A-D deletion (2.1%, 23/1118). Most of the 16p11.2 deletions (8/10) detected were de novo, and were enriched in CHD cases compared with a control cohort from a previous study. Additionally, SV was identified in 12.9% (8/62) of cases without NCA and P/LP CNV, most of which were de novo with autosomal dominant inheritance.ConclusionsOur cohort study provides a deep profile of the contribution of genetic variants to CHDs in both singleton and twin fetuses; NCA and P/LP CNV contribute to 9.1% and 8.5% of CHD in fetuses, respectively. We confirmed the 16p11.2 deletion as a CHD-associated hotspot CNV, second only to the 22q11.21 deletion in frequency. Most 16p11.2 deletions detected were de novo. Additionally, P/LP SV was identified in 12.9% (8/62) of fetuses without NCA or P/LP CNV.

Determination of the ovine ovarian reserve during the prenatal and neonatal periods

Objective: To determine the ovine ovarian histomorphology and follicular staging at various age periods in Awassi breed. Methods: Ovaries were collected from prenatal fetuses [gestational age (95±5) days], neonatal (day 0), and prepubertal ewe lambs (two and four months of age); each age group included six animals. Ovaries (n=12, each group) were dissected and processed for hematoxylin and eosin staining. Stained sections (n=24, each group) were imaged and utilized for histomorphology assessment, follicle measurement, and classification. Results: Prenatal ovaries were mainly enriched with primordial follicles accompanied by a lower proportion of primary follicles. In addition to primordial and primary follicles, neonatal ovaries demonstrated a proportion of centrally located multilayered and antral follicles. In comparison with neonatal ovaries, the proportion of multilayered and antral follicles was significantly higher in the ovaries of two-month-old lambs; conversely, the proportion of peripherally situated primordial follicles dramatically declined compared to that of earlier age of lamb. Although there was no statistical variation in the sizes of primordial follicles across groups, the mean diameter of the primary follicle in the prenatal ovaries was substantially smaller than in postnatal ovaries. Compared to the neonatal ovaries, the size of the multilayered and antral follicles in the prepubertal ovaries was substantially larger. Conclusions: The earliest follicular developmental stages were established prenatally whereas the advanced growth stages started in the neonatal period and greatly increased in the prepubertal period.

GLA GENE MUTATION IN PATIENTS WITH FABRY DISEASE

Introduction: For the first time in the Lenkoran-Astara administrative area of Azerbaijan Republic, a genetic screening was conducted on patients with cardiomyopathies to identify Fabry metabolic disease. The screening involved the assessment of alpha-galactosidase enzyme activity and the globotriasylsphingosine level. This article aims to present the results of the screening and the subsequent molecular genetic analysis of the GLA gene in the identified patients. Materials and Methods. The genetic screening was based on applying fluorimetry and liquid chromatography methods. The Sanger sequencing technique was employed for direct sequencing of the GLA gene, enabling the detection of existing mutations. This technique was developed in CENTOGENE laboratories, Rostock, Germany. The initial tests were conducted at the Centogene laboratory in Rostock, Germany, followed by further testing at the GENOM clinical laboratory in Baku, Azerbaijan Republic. Ultrasonic and echocardiography studies were performed simultaneously with blood sampling at the central regional hospital. Results: 21 individuals out of 76 involved in the study had a deficiency in αgalactosidase enzyme activity and elevated levels of globotriasylsphingosine, indicative of Fabry disease. Among them, seven women exhibited X-linked inheritance as heterozygous, and three men were identified as homozygous. Molecular genetic analysis revealed two different mutations in the GLA gene: 801+3A&gt;G and 137 A&gt;G. To prevent Fabry disease, it is recommended to screen family members of affected individuals for α-galactosidase enzyme activity. Conclusion: This study represents the first genetic screening for Fabry disease conducted in the Azerbaijan Republic among patients with cardiological diseases. 21 individuals out of 76 examined patients were identified as having Fabry disease and carrying two different GLA gene mutations: c.801+3A&gt;G and c.137A&gt;G. The obtained genetic results will aid cardiologists to make accurate diagnosis and to select appropriate management for patients with cardiomyopathy, considering the presence of Fabry disease, as well as enabling prenatal foetus diagnostics during pregnancies in families at genetic risk.

Large abdominal cyst of the fetus: A rare diagnosis of neonatal megaduodenum

We present a rare case of neonatal duodenal malformation. Herein, we provide a differential diagnosis for a large abdominal cyst in a prenatal fetus and explore the possible causes and treatment of neonatal megaduodenum. We retrospectively analyzed one case of megaduodenum from fetal examination to neonatal diagnosis and treatment. Ultrasonography of the fetus at 12 weeks' gestation revealed a cystic mass in the abdominal cavity, measuring about 0.7 cm × 0.5 cm × 0.4 cm. The cystic mass grew in equal proportion to the fetus. At 32 weeks’ gestation, the peritoneal cystic mass was enlarged to 9.0 cm × 7.9 cm × 5.8 cm, and the mass was found to be communicating with the stomach. Intraoperatively, the mass was about 10-cm long and 6 cm in diameter. The duodenal papilla was located about 1.5 cm above the proximal junction. The megaduodenum was removed, and the distal and proximal intestines were anastomosed end-to-end. The patient recovered smoothly postoperatively and gained 550 g 1 month after discharge. The results of amniotic fluid high-throughput sequencing identified Seq [Grch37] del (16) (p12.2) Chr16: g.22000000_22440000del. There was a copy number deletion of about 0.44 Mb on the short arm of chromosome 16, which was suspected to be pathogenic and involved seven protein-coding genes. Histopathologically, in the same paraffin specimen, there was a mixture of stunted ganglion cells, ganglion dysplasia, and well-developed ganglion cells. Neonatal megaduodenum was considered as a differential diagnosis of the large cystic mass in the fetal abdomen. Further additional evidence was needed to prove whether the mutation was pathogenic, which also suggested that the etiology is related to genetic variation. The nerve plexus and ganglion cells were poorly developed, which further supported that the intestinal nerve abnormality was the etiology. Excision was safe and effective for treating megaduodenum.

Prenatal diagnosis of fetal growth restriction with polyhydramnios, etiology and impact on postnatal outcome

To assess the spectrum of different etiologies, the intrauterine course, outcome and possible prognostic markers in prenatally detected fetal growth restriction (FGR) combined with polyhydramnios. Retrospective study of 153 cases with FGR combined with Polyhydramnios diagnosed by prenatal ultrasound over a period of 17 years. Charts were reviewed for ultrasound findings, prenatal and postnatal outcome. All cases were categorized into etiological groups and examined for differences. Five etiological groups were identified: chromosomal anomalies (n = 64, 41.8%), complex malformation syndromes (n = 37, 24.1%), isolated malformations (n = 24, 15.7%), musculoskeletal disorders (n = 14, 9.2%) and prenatal non-anomalous fetuses (n = 14, 9.2%). Subgroups showed significant disparities in initial diagnosis of combination of both pathologies, Ratio AFI/ gestational weeks and Doppler ultrasound examinations. Overall mortality rate was 64.7%. Fetuses prenatally assigned to be non-anomalous, showed further complications in 42.9% (n = 6). Fetuses prenatally diagnosed with FGR combined with polyhydramnios are affected by a high morbidity and mortality. Five etiologic groups can be differentiated, showing significant disparities in prenatal and postnatal outcome. Even without recognizable patterns prenatally, long-term-follow up is necessary, as neurodevelopmental or growth delay may occur.

Prenatal and Postnatal Detection of Fetal Structural Defects by Abdominal Ultrasound and Physical Examination in Azadi Teaching Hospital in Kirkuk City

Background: The prevalence of birth defects increased abruptly in recent years especially in Iraq. The etiology may be related to either genetic or environmental factors. Material & Method: In this cross sectional study that is conducted in Azadi Teaching Hospital in Kirkuk city in Sonographic unit & delivery room. A total of 1814 prenatal fetuses and postnatal newborns with their mothers were involved in this study. All the fetuses or newborns were examined for search of different fetal structural defects. The aim of the study: Was to identify the prevalence of fetal structural defects among pregnant women who attending Azadi Teaching Hospital. Results: Neurological defects were the most frequent detected anomaly (58.8%) followed by skeletal defects (15.4%), (10.3%) for hydropsfetalis, (7.7%) for urinary system defects, (7.7%) for cystic hygroma and only (5.1%) for facial defects. The anomaly detection rate by trans-abdominal ultrasound was (1.9%) during 2nd and 3rd trimesters, and postnatal diagnosis by physical examination was (2.5%). Conclusion: The following factors were found to involve in the etiology of fetal structural defects; family history of congenital anomalies, maternal age, multigravidas mothers, taking tonics and supplements during pregnancy, smoking, living in rural areas finally socioeconomic status.

Effect of Hair Coat Shedding Ability on Uterine Artery Hemodynamics in Angus Cattle

Abstract The objective of this study was to evaluate winter hair coat shedding ability and its association with uterine artery hemodynamics. Fall calving, artificially inseminated purebred Angus females (n = 29) were observed once monthly by two trained technicians for winter hair coat shedding and given a visual hair shedding score of 1 to 5 with 1 indicating 100% shed, 2 = 75%, 3 = 50%, 4 = 25%, and 5 indicating 0% shedding of winter hair coat. Month of first shedding (MFS) was determined once a female reached an average hair shedding score of ≤ 3.5 from March until July of 2019 and 2020. Uterine artery blood flow (ABF) was determined using color Doppler ultrasonography at d 150, 180, 210, and 240 of gestation. Total uterine artery (summation of ipsilateral and contralateral arteries) and ipsilateral uterine ABF, diameter, resistance and pulsatility index (PI) were analyzed using repeated measures of the MIXED procedure of SAS with significance declared at P ≤ 0.05. Fixed effects included MFS, day, year, and the respected interactions with covariates of dam body weight, ambient temperature and order of cows ultrasonography examination considered as a random effect. No significant MFS by day of gestation interaction (P &amp;gt; 0.32) was observed for total or ipsilateral ABF (P &amp;gt; 0.23). A MFS by day of gestation (P &amp;lt; 0.04) interaction was observed for both ipsilateral artery diameter and PI, in which females that shed by May had smaller artery diameter (0.74 vs. 0.85 cm) at day 180 of gestation and greater PI (P &amp;lt; 0.02; 1.48 vs. 1.03) at day 150 of gestation compared to June. Shedding ability had an effect on ipsilateral uterine artery development and pulsatility during gestation, possibly affecting the amount of nutrients distributed to the prenatal fetus and subsequent birth weight of the calf from females that shed by May.

The Effects of Different Concentrations of Retinoic Acid on the Histological Structure of Liver of Adult Albino Female Mice and Their Prenatal Fetuses

Retinoic acid (RA) an active metabolite of vitamin A, plays essential signaling roles in mammalian embryonic development and adult homeostasis through concentration-dependent activity but in excess, RA is teratogenic. The present study was designed to evaluate the harmful effect of RA on the: liver tissues of the adult pregnant female albino mice and their prenatal fetuses and adult morphological and behavior changes. Forty-five pregnant adult female albino mice were divided into three groups (n=15 for each group). Group I, the control group orally received 0.1ml of olive oil. Group II and III received 25 and 50mg RA/kg B.W. respectively. RA was dissolved in 0.1ml of olive oil and orally given on 7 th , 8 th , and 9 th days of pregnancy. On the 18 th day of gestation, these females were sacrificed and the liver from mother and their prenatal were removed, weighed, and prepared for histological study. The RA treated adult group exhibited behavior changes including general fatigue and loss of appetite, in addition to the morphological changes which included weight loss, change in normal red eye color towards black, and redness in the mouth and chin area associated with loss of hair (fur) around this area. These observations were showed to be more severe in the 50 mg RA group. The results showed that treatment with 25 and 50mg RA caused no significant decrease in the adult liver weight, while in their prenatal fetuses 50mg RA caused a higher significant decrease in the liver weight, but 25 mg RA caused no significant effects on this weight. Treated with 50mg/kg RA caused a highly significant increase in the number of aborted and dead fetuses as compared with other groups. The results of the histological study showed that treatment with both concentrations of RA caused several degrees of the liver damage with disrupted the normal architecture pattern along with hepatocellular steatosis, hypertrophy, and inflammation. In conclusions, RA caused variable degrees of degeneration and destruction of the liver tissues of adult female (mother) and their prenatal. The most important effects of RA are causing hepatocellular steatosis, hypertrophy, and inflammation, and when RA giving during the critical periods of embryonic development, caused harmful effects on the developing liver, therefore treatment with RA should be avoided at any stage of gestation. Keywords: Liver, retinoic acid, embryonic development, vitamin A, histological study. DOI: 10.7176/JBAH/10-18-04 Publication date: September 30 th 2020

Maternal physiological and psychological factors and its impact on foetus outcome: A scoping review

Low birth weight (LBW), prematurity and intrauterine growth retardation (IUGR) remains the leading causes of perinatal morbidity, mortality, neurodevelopmental impairments and disabilities among newborn babies (WHO 1995) The belief that a mother’s psychological status may affect her foetus has been common in every society, since ancient times. The study aims to explore the literature revealing impact of maternal nutrition, maternal stress on the Foetus growth, and on pregnancy outcome. The literature regarding effects of prenatal maternal stress and diet on Foetus outcomes was obtained from numerous journals and peer-reviewed articles on Pubmed, MEDLINE, Embase and Google Scholar till 2018 using Boolean combinations of the terms ‘maternal nutrition’, ‘maternal stress’, ’maternal occupational stress’, ‘foetus growth’, ‘pregnancy outcome’. Ample of research work is conducted on maternal dietary practices and its impact on foetus growth in other countries as well as in India. But Maternal psychological stress and its impact on foetus growth is rarely studied in global scenarios and much rare in India. The study reveals that the maternal stress during pregnancy causes poor development of foetus also affects the cognitive and behavioural development of children in their later life. Impact of stress varies in function with type of stress, gestational period during which it occurs. The present review was conducted to have a better idea about prenatal maternal stress and poor Foetus outcome. The study suggests that addressing pregnancy related health issues is important in order to appropriate strategies to promote and protect maternal and infant health.

Morphological and osteological studies on the effect of acrylamide (ACR) on paternally treated fetuses of albino rat

The present study investigates the effects of Acrylamide (ACR) on the skeletal system of the prenatal fetuses of 20th day of gestation of rat. The used rat were arranged in five groups; Control group (C) was the group treated orally by distilled water; G1 was the group of male treated daily with (10 mg/kg) of ACR orally for 10 days and then they allowed to mate with control females.G2 was the group of female treated daily with (10 mg/kg) of ACR orally for 10 days and then they allowed to mate with control males. G3 was the group of male and female treated daily with (10 mg/kg orally) of ACR orally for 10 days and then they allowed to mate with each other.G4 was the group of Pregnant female treated daily with (10 mg/kg) of ACR orally at (1st -20th) day of Pregnancy. At the 20th day of gestation, the uteri were removed by cesarean sections. For each mother, the number of fetal swelling in each horn, living and dead fetuses and early of late resorptions were recorded. Early and late resorptions were discerned according to their size. For morphological studies, fetuses either living or dead were counted, weighed and measured then morphologically examined for any external malformation. Stereoscopic examination for the obtained 20th day of gestation. Fetuses showed severe skeletal alterations included incomplete ossification for some bones of skull, vertebrae, fore and hind limbs and significant reduction in the length of most long bones of both limbs. The alterations indicated that ACR treatment induced growth retardation confirmed by great reduction in body weight and body length. The results suggest that ACR has Teratogenic effects on maternally treated 20-day-old albino rat fetuses.

Topographoanatomic features and histochemical changes in thymus of germ and forebrain in the prenatal period of the human in the prenatal period

In this study, histochemical changes were studied and topographic anatomical relationships of thymus (T) germs and prenatal human fetus in the prenatal period with general histological, cytotoxic and lectinogenic chemical methods were analyzed for the study of the development and the possibility of argumentation of the source of epithelium swelling of the digestive tract; graphic and plastic reconstructions, macroscopic painting. It is established that for organogenesis of T during the embryonic period it is characteristic of: loss of connections with the pharynx, close interaction of paired gums with each other, with topographic anatomically adjacent organs and with vascular-nervous formations of this area (thyroid and parathyroid glands, larynx, pharynx, esophagus; aorta, carotid arteries, trunks of the vagus nerve, inferior and superior laryngeal nerves). The dimensions of the rudiments and the form of T of this age period are dynamically changing depending on the process of growth (lowering) of the rudiments. For T the latter are correlated with the formation of large vessels and nerve trunk of the neck. The displacement of the rudiments of the T is by lateral walls of the formed and recognized common carotid arteries and the medial surfaces of the vagus nerves in the ventrocaudal direction. There is an asynchronous lowering of the rudiments of the particles of the T, since the left embryo of the particle with its displacement outstrips the right. It should be noted that during the course of the study we did not detect congenital malformations of the development of T, which, obviously, was the result of the proper selection of the research material and use in the future. Prospects for further development are the study of the laws of the structure and the formation of the fetal gland and structures of different systems in the fetal of human perinatal ontogenesis.

Gut microbiota-derived endotoxin enhanced the incidence of cardia bifida during cardiogenesis.

Cytotoxicity and inflammation-associated toxic responses could be induced by bacterial lipopolysaccharides (LPS) in vitro and in vivo, respectively. However, the mechanism involved in LPS-induced cardiac malformation in prenatal fetus is still unknown. In this study, we demonstrated that LPS was induced in gut microbiota imbalance mice, and next, LPS exposure during gastrulation in the chick embryo increased the incidence of cardia bifida. Gene transfection and tissue transplantation trajectory indicated that LPS exposure restricted the cell migration of cardiac progenitors to primary heart field in gastrula chick embryos. In vitro explant allograft of GFP-labeled anterior primitive streak demonstrated that LPS treatments could inhibit cell migration. A similar observation was also obtained from the cell migration assay of scratch wounds using primary culture of cardiomyocytes or H9c2 cells. In the embryos exposed to LPS, expressions of Nkx2.5 and GATA5 were disturbed. These genes are associated with cardiomyocyte differentiation when heart tube fusion occurs. Furthermore, pHIS3, C-caspase3 immunohistological staining indicated that cell proliferation decreased, cell apoptosis increased in the heart tube of chick embryo. Meanwhile, in vivo, pHIS3 immunohistological staining and Hochest/PI staining also draw the similar conclusions. The LPS exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. At last, we showed that LPS-induced cardia bifida could be partially rescued through the addition of antioxidants. Together, these results reveal that excess ROS generation is involved in the LPS-induced defects in heart tube during chick embryo development.

Pregabalin administration induces alterations in neural tube development during early embryonic stages.

Antiepileptic drugs (AEDs) have been known to cause congenital malformations, including neural tube defects. However, inadequate data are available regarding the effects of recently developed AEDs, such as pregabalin. The present study was conducted to evaluate the effect of pregabalin on neural tube development using early chick embryos. Experiments were conducted on specific pathogen-free Leghorn chick embryos, which were equally divided into control and pregabalin-treated (therapeutic dose, 600 mg; supratherapeutic dose, 1200 mg) groups. The embryos were macroscopically and microscopically evaluated following pregabalin administration. Expression levels of mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase (JNK), and microtubule-associated proteins 1A/1B light chain 3 (LC3) in the embryos were observed. The embryos in the therapeutic dose group appeared more curved than those in the control group. The vesicles in the supratherapeutic dose group were more distinct but smaller than those in the control and therapeutic dose groups. mTOR expression was high in the control group and low in the therapeutic and supratherapeutic dose groups. JNK expression was low in the control and therapeutic dose groups and moderate in the supratherapeutic dose group. LC3 expression was moderate in the control and therapeutic dose groups and strong in the supratherapeutic dose group. Pregabalin administration induced neural tube defects and fetal abnormalities in the chick embryos through increased autophagy due to enhanced apoptosis in the prenatal fetus.

The clinical use of chromosomal microarray analysis in detection of fetal chromosomal rearrangements: a study from China Mainland

ObjectivesThis study aimed to evaluate the detection rate of chromosomal microarray analysis (CMA) in prenatal fetuses compared with conventional karyotype and to assess the additional diagnostic yields of CMA in groups of different indications. Study DesignA total of 217 fetuses were divided into seven groups according to different indications. All cases were tested by both CMA and karyotype. The detection rates of CMA and karyotype were evaluated. The increased value of CMA in each group was also calculated. ResultsA total of 35 cases were detected to have a pathogenic result by CMA, indicating the overall detection rate of 16.1%. Nine more cases were detected only by CMA, indicating an incremental diagnostic yield of 4.2%. The highest incremental value was observed in fetuses with structural defects (6.6%). In 11 cases with known abnormal chromosome anomalies, CMA revealed additional information over conventional karyotyping in 4 fetuses. ConclusionsThe present study convincingly demonstrated the efficiency of CMA in detecting feal chromosomal rearrangements. CMA significantly improves the detection rate in fetuses with structural defects and provides helpful information for fetuses with known abnormal chromosomes but without clear diagnosis.

Effect of experimental phenylketonuria on the development of skin of prenatel and newborn fetuses.

Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. The present work studied the Effect of experimental phenylketonuria on the development of skin of prenatel and newborn fetuses.The disease was induced in pregnant rats by daily intragastric administration of 30 mg. DL-a-methylphenylalanine/kg body weight plus 60 mg/kg body weight at 12 h intervals throughout pregnancy till parturition. Treatment with alpha-methylphenylalanine/phenylalanine resulted in significant decrease of accumulated body weight gain during pregnancy as well as exhibited marked growth retardation of prenatal fetuses and delivered newborn. The growth retarded fetuses was manifested by decreased body weight, malformed both fore -& hind limb, oedematous skin & superficial hematomas widely spreads in different parts of the body. Vibrissae skin hair were characterized by curved free ends as well as reduction of their size and length. Cornification was retarded . The epidermis attained a considerable thinning with delayed differentiation of epidermal cell layers.The growing hair follicles lacked normal characteristic appearance. These results suggested that exposure of the fetus to high plasma concentrations of phenylalanine caused a delay in the biochemical maturation of the fetal rat.

Determination of the Genital Structures using Ultrasound in Canine Prenatal Fetuses

Determination of the Genital Structures using Ultrasound in Canine Prenatal Fetuses

Eyelid closure in embryogenesis is required for ocular adnexa development.

Mammalian eye development requires temporary fusion of the upper and lower eyelids in embryogenesis. Failure of lid closure in mice leads to an eye open at birth (EOB) phenotype. Many genetic mutant strains develop this phenotype and studies of the mutants lead to a better understanding of the signaling mechanisms of morphogenesis. The present study investigates the roles of lid closure in eye development. Seven mutant mouse strains were generated by different gene ablation strategies that inactivated distinct signaling pathways. These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in stratified epithelium (SE), as well as the Map3k1/Jnk1 and Map3k1/Rhoa compound mutants, all exhibited defective eyelid closure. The embryonic and postnatal eyes in these mice were characterized by histology and immunohistochemistry. Some eye abnormalities, such as smaller lens in the Map3k1-null mice and Harderian gland hypoplasia in the Dkk2-null mice, appeared to be mutant strain-specific, whereas other abnormalities were seen in all mutants examined. The common defects included corneal erosion/ulceration, meibomian gland hypoplasia, truncation of the eyelid tarsal muscles, failure of levator palpebrae superioris (LPS) extension into the upper eyelid and misplacement of the inferior oblique (IO) muscle and inferior rectus (IR) muscle. The muscle defects were traced to the prenatal fetuses. In addition to providing a protective barrier for the ocular surface, eyelid closure in embryogenesis is required for the development of ocular adnexa, including eyelid and extraocular muscles.

MALFORMATIONS INDUCED IN THE SKELETAL SYSTEM OF MOUSE FETUSES BY THE FOOD PRESERVATIVE SODIUM BENZOATE

The present study delt with the teratogenic effects of sodium benzoate (SB), which is used as a food preservative and antimicrobial agent on the skeletal system of the prenatal fetuses of mice on day 18 of gestation. The used low and high doses of SB were found to be 200 and 500 mg/kg body weight. The pregnant mice were divided into four groups; control and three SB-treated groups (G1, G2 & G3). Each treated group was divided into two sub-groups for treatment with low and high doses of SB. This study revealed that most elements of fetuses skull showed moderate to severe malformations. Ossification of the centra of some cervical vertebrae were absent especially at the high dose in group 2. The high dose of sodium benzoate showed some unossified caudal vertebrae especially in groups 2 and 3. The whole sternum and xiphoid cartilage became shorter than the control in all groups treated with low and high doses of SB. The cartilaginous portion of the ribs exhibited less blue colouration than the control denoting reduction in its chondrification. Also, some ribs showed curled appearance. In addition, the scapula and clavicle of the pectoral girdle were shorter and less thickened in all treated groups. The long bones of the fore and hind limbs in the high dose treated groups were shorter in length and decreased in thickness compared to those of the control. In such case, the density of red coloration was less than the control.

Repair and regeneration in endodontics

The ideal objective of treatment of established diseases, including irreversible pulpitis and apical periodontitis, is to achieve wound healing. Wound healing can result in repair or regeneration. The ultimate goal of wound healing is to restore the original architecture and biological function of the injured tissue or organ. Although humans are equipped with powerful innate and adaptive immune defence mechanisms, many intrinsic and extrinsic factors can affect wound healing. Complete regeneration following injury in humans can occur only in the pre-natal foetus within 24 weeks of gestation. Post-natal wounds including irreversible pulpitis or apical periodontitis always heal by repair or by a combination of repair and regeneration. Somatic cells, such as fibroblasts, macrophages, cementoblasts and osteoblasts, in the pulp and periapical tissues have limited potential for regeneration following injury and lack of telomerase. Wound healing of irreversible pulpitis and apical periodontitis requires recruitment and differentiation of progenitor/stem cells into tissue-committed somatic cells. Stem cell differentiation is regulated by intrinsic factors and extrinsic micro-environmental cues. Functionality of stem cells appears to show an age-related decline because of the change in intrinsic properties and diminished signals within the extrinsic local and systemic environment that modulate the function of stem cells or their progeny. Infection induces an immuno-inflammatory response and tissue destruction, which hinders the potential of tissue regeneration. Therefore, prevention, early detection and treatment of inflammation/infection of pulpal and periapical disease can enhance regeneration and minimize the repair of pulpal and periapical tissues after endodontic therapy.

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities.

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping.In the UK, RAD is recommended as a standalone approach in DSSP, whereas the US guidelines recommend that RAD be followed up by karyotyping. A cost-effectiveness (CE) analysis of RAD in various DSSP is lacking. There is a debate over the significance of chromosome abnormalities (CA) detected with karyotyping but not using RAD. Our objectives were to compare the CE of RAD versus karyotyping, to evaluate the clinically significant missed CA and to determine the impact of detecting the missed CA. We performed computer simulations to compare six screening options followed by FISH, PCR or karyotyping using a population of 110 948 pregnancies. Among the safer screening strategies, the most cost-effective strategy was contingent screening with QF-PCR (CE ratio of $24 084 per Down's syndrome (DS) detected). Using karyotyping, the CE ratio increased to $27 898. QF-PCR missed only six clinically significant CA of which only one was expected to confer a high risk of an abnormal outcome. The incremental CE ratio (ICER) to find the CA missed by RAD was $66 608 per CA. These costs are much higher than those involved for detecting DS cases. As the DSSP are mainly designed for DS detection, it may be relevant to question the additional costs of karyotyping.