Fetal Research Articles

Quantitative anatomy of the extensor digiti minimi muscle in the growing human fetus.

Introduction Age-specific reference intervals for the extensor digiti minimi muscle (EDMM) in the human fetus may be relevant in the detailed evaluation of the musculoskeletal systems with potential relevant aspects for surgical treatment. The aim of the study was to examine the age-specific reference intervals and growth dynamics of the EDMM in relation to its length, width, projection surface area and volume. Material and methods The examined material included 70 human formalin-fixed fetuses of both sexes (37♀, 33♂) aged from 17 to 29 weeks. With the use of anatomical dissection every EDMM was visualized, recorded in a form of JPG formats and analyzed by the digital image analysis system and statistical methods. Results No variability of the EDMM was found. All the morphometric parameters of the EDMM revealed neither sex nor laterality differences. With fetal age most linear parameters of the EDMM concerning its examined lengths and widths increased in accordance with natural logarithmic functions. The only two exceptions to this referred to the belly width of EDMM measured at its mid-length and the tendon width of EDMM measured proximal to the extensor retinaculum of wrist, which both followed square root functions. The projection surface areas of the EDMM followed natural logarithmic functions, while the volumetric growth of the EDMM was proportionate to fetal age. Conclusions The variability of the EDMM in the human fetus is minimal. The morphometric data of the EDMM represents age-specific reference intervals of clinical significance. Morphometric parameters of the EDMM reveal neither sex nor laterality differences. The EDMM displays three different growth dynamics: from gradual growth deceleration according to both natural logarithmic functions (total length of the muscle and its tendons, belly length, tendon lengths, belly width at its origin, tendon width at its insertion, and projection surface areas) and square root functions (belly width at its mid-length and tendon width in the pre-retinacular segment) to a proportionate growth (total volume).

Anatomical study with clinical significance of communicating and visceral branching of the cervical and upper thoracic sympathetic trunk.

Current advances in the management of the autonomic nervous system in various cardiovascular diseases, and in treatments for pain or sympathetic disturbances in the head, neck, or upper limbs, necessitate a thorough understanding of the anatomy of the cervicothoracic sympathetic trunk. Our objective was to enhance our understanding of the origin and distribution of communicating branches and visceral cervicothoracic sympathetic nerves in human fetuses. This was achieved through a comprehensive topographic systematization of the branching patterns observed in the cervical and upper thoracic ganglia, along with the distribution of communicating branches to each cervical spinal nerve. We conducted detailed sub-macroscopic dissections of the cervical and thoracic regions in 20 human fetuses (40 sides). The superior and cervicothoracic ganglia were identified as the cervical sympathetic ganglia that provided the most communicating branches on both sides. The middle and accessory cervical ganglia contributed the fewest branches, with no significant differences between the right and left sides. The cervicothoracic ganglion supplied sympathetic branches to the greatest number of spinal nerves, spanning from C5 to T2. The distribution of communicating branches to spinal nerves was non-uniform. Notably, C3, C4, and C5 received the fewest branches, and more than half of the specimens showed no sympathetic connections. C1 and C2 received sympathetic connections exclusively from the superior ganglion. Spinal nerves that received more branches often did so from multiple ganglia. The vertebral nerve provided deep communicating branches primarily to C6, with lesser contributions to C7, C5, and C8. The vagus nerve stood out as the cranial nerve with the most direct sympathetic connections. The autonomic branching pattern and connections of the cervicothoracic sympathetic trunk are significantly variable in the fetus. A comprehensive understanding of the anatomy of the cervical and upper thoracic sympathetic trunk and its branches is valuable during autonomic interventions and neuromodulation. This knowledge is particularly relevant for addressing various autonomic cardiac diseases and for treating pain and vascular dysfunction in the head, neck, and upper limbs.

Growing stylohyoideus muscle insertion to the hyoid bone with special reference to its topographical relation to the intermediate tendon of digastricus muscle: A histological study using human fetuses

BackgroundIn adults, the intermediate tendon of digastricus muscle usually runs along the medial or lateral side of the stylohyoideus muscle insertion. To provide a better understanding of the variations, we examined the topographical anatomy of the muscle and tendon in fetuses. MethodsWe examined histological sections from six early-term, 26 mid-term and six near-term fetuses (approximately 8–9, 12–18 weeks and 25–33 weeks). ResultsAt early-term, an initial sheath of intermediate tendon of digastricus muscle received the stylohyoideus muscle at the superior aspect. The muscle and tendon was distant from the hyoid. At mid-term, near the insertion to the hyoid greater horn, the stylohyoideus muscle consistently surrounded more than 2/3 of the intermediate tendon circumference. In contrast, we found no near-term specimen in which the stylohyoideus muscle surrounded the intermediate tendon. The multilayered tendon sheath was fully developed until near-term and connected to the body of hyoid by an intermuscular septum between the thyrohyoideus muscle and one or two of suprahyoid muscles. Therefore, the hyoid insertion of the styloglossus muscle was a transient morphology at mid-term. ConclusionThe stylohyoideus muscle insertion was appeared to move from the tendon sheath to the hyoid greater horn and, until near-term, return to the tendon sheath. A fascia connecting the tendon sheath to the body of hyoid was strengthened by the suprahyoid and infrahyoid muscles. The latter muscles seemed to regulate fixation/relaxation of the intermediate tendon to the hyoid. The stylohyoideus muscle slips sandwiching the intermediate tendon might be a rare morphology.

Growth of the brachial nerve plexus with reference to topographical relation of the medianus nerve ansa with the thoracic wall and shoulder: a histologic study using human embryos and fetuses.

There is currently no information on positional changes in the brachial nerve plexus during prenatal growth. The subclavian-axillary artery passing through the medianus nerve ansa is considered a good landmark for evaluating the height of the plexus. We used histologic sections from 9 embryos and 17 fetuses (approximately 6-15weeks of gestational age) to identify the height of the ansa by referring to the level of the rib and the glenohumeral joint. The nerve ansa was usually (23 plexuses) observed at the level of the first and/or second ribs. However, it was sometimes observed above the first rib, at a distance equal to or more than an intercostal width (7 plexuses). In the latter group, the ansa was usually located below the glenohumeral joint. Thus, the joint was located higher than the first rib, although the upper extremities were in the anatomic position for all specimens. The left-right difference in the height of the plexus corresponded to or was less than the width of the first intercostal space. Despite the synchronized growth between the thorax and shoulder girdle, the brachial plexus showed a considerable variation in comparative height; the range corresponded to twice of an intercostal width. Whether the nerve plexus is located high or low is determined at an early developmental stage and is maintained during the later growth stages. The high-positioned plexus might cause nerve injury at delivery, followed by a glenohumeral joint deformity because of the fragility without fixation in the thorax.

Cochlear aqueduct revisited: A histological study using human fetuses

Background and aimThe cochlear aqueduct (CA) connects between the perilymphatic space of the cochlea and the subarachnoid space in the posterior cranial fossa. The study aimed to examine 1) whether cavitation of the CA occurs on the subarachnoid side or the cochlear side and 2) the growth and/or degeneration of the CA and its concomitant vein. MethodsWe examined paraffin-embedded histological sections from human fetuses: 15 midterm fetuses (crown-rump length or CRL, 39–115 mm) and 12 near-term fetuses (CRL, 225–328 mm). ResultsA linear mesenchymal condensation, i.e., a likely candidate of the CA anlage, was observed without the accompanying vein at 9–10 weeks. The vein appeared until 15 weeks, but it was sometimes distant from the CA. At 10–12 weeks, the subarachnoid space (or the epidural space) near the glossopharyngeal nerve rapidly protruded into the CA anlage and reached the scala tympani, in which cavitation was gradually on-going but without epithelial lining. However, CA cavitation did not to occur in the anlage. At the opening to the scala, the epithelial-like lining of the CA lost its meningeal structure. At near-term, the CA was often narrowed and obliterated. ConclusionThe CA develops from meningeal tissues when the cavitation of the scala begins. The latter cavitation seemed to reduce tissue stiffness leading, to meningeal protrusion. The so-called anlage of CA might be a phylogenetic remnant of the glossopharyngeal nerve branch. A course of cochlear veins appears to be determined by a rule different from the CA development.

The Auditory Pathway in Congenitally Cytomegalovirus-Infected Human Fetuses.

Congenital cytomegalovirus (CMV) infection is the main cause of non-hereditary sensorineural hearing loss (SNHL). In order to shed light on SNHL pathophysiology, we examined the auditory pathway in CMV-infected fetuses; the temporal lobe, in particular the auditory cortex, and the inner ear. We investigated both inner ears and temporal lobes of 20 human CMV-infected fetuses at 21 weeks of gestation. As a negative group, five fetuses from spontaneous miscarriages without CMV infection were studied. Inner ears and temporal lobes were histologically examined, immunohistochemistry for CMV and CMV-PCR were performed. On the auditory cortex, we evaluated the local microglial reaction to the infection. CMV-positive cells were found in 14/20 brains and the damage was classified as severe, moderate, or mild, according to histological features. Fetuses with severe brain damage had a statistically higher temporal lobe viral load and a higher number of activated microglial cells in the auditory cortex compared to fetuses with mild brain damage (p: 0.01; p: 0.01). In the inner ears, the marginal cells of the stria vascularis were the most CMV positive. In our study, CMV affected the auditory pathway, suggesting a tropism for this route. In addition, in the auditory cortex, microglial activation may favor further tissue damage contributing to hearing loss.

Blastocyst telomere length predicts successful implantation after frozen-thawed embryo transfer.

Do embryos with longer telomere length (TL) at the blastocyst stage have a higher capacity to survive after frozen-thawed embryo transfer (FET)? Digitally estimated TL using low-pass whole genome sequencing (WGS) data from the preimplantation genetic testing for aneuploidy (PGT-A) process demonstrates that blastocyst TL is the most essential factor associated with likelihood of implantation. The lifetime TL is established in the early cleavage cycles following fertilization through a recombination-based lengthening mechanism and starts erosion beyond the blastocyst stage. In addition, a telomerase-mediated slow erosion of TL in human fetuses has been observed from a gestational age of 6-11 weeks. Finally, an abnormal shortening of telomeres is likely involved in embryo loss during early development. Blastocyst samples were obtained from patients who underwent PGT-A and FET in an IVF center from March 2015 to May 2018. Digitally estimated mitochondrial copy number (mtCN) and TL were used to study associations with the implantation potential of each embryo. In total, 965 blastocysts from 232 cycles (164 patients) were available to investigate the biological and clinical relevance of TL. A WGS-based workflow was applied to determine the ploidy of each embryo. Data from low-pass WGS-PGT-A were used to estimate the mtCN and TL for each embryo. Single-variant and multi-variant logistic regression, decision tree, and random forest models were applied to study various factors in association with the implantation potential of each embryo. Of the 965 blastocysts originally available, only 216 underwent FET. While mtCN from the transferred embryos is significantly associated with the ploidy call of each embryo, mtCN has no role in impacting IVF outcomes after an embryo transfer in these women. The results indicate that mtCN is a marker of embryo aneuploidy. On the other hand, digitally estimated TL is the most prominent univariant factor and showed a significant positive association with pregnancy outcomes (P < 0.01, odds ratio 79.1). We combined several maternal and embryo parameters to study the joint effects on successful implantation. The machine learning models, namely decision tree and random forest, were trained and yielded classification accuracy of 0.82 and 0.91, respectively. Taken together, these results support the vital role of TL in governing implantation potential, perhaps through the ability to control embryo survival after transfer. The small sample size limits our study as only 216 blastocysts were transferred. The number was further reduced to 153 blastocysts, where pregnancy outcomes could be accurately traced. The other limitation of this study is that all data were collected from a single IVF center. The uniform and controlled operation of IVF cycles in a single center may cause selection bias. We present novel findings to show that digitally estimated TL at the blastocyst stage is a predictor of pregnancy capacity after a FET cycle. As elective single-embryo transfer has become the mainstream direction in reproductive medicine, prioritizing embryos based on their implantation potential is crucial for clinical infertility treatment in order to reduce twin pregnancy rate and the time to pregnancy in an IVF center. The AI-powered, random forest prediction model established in this study thus provides a way to improve clinical practice and optimize the chances for people with fertility problems to achieve parenthood. This study was supported by a grant from the National Science and Technology Council, Taiwan (MOST 108-2321-B-006-013 -). There were no competing interests. N/A.

Growth of muscles and nerves in the upper eyelid: a morphometrical and immunohistochemical study using term human fetuses.

There is no information about muscle growth in eyelids with infrequent blinking in fetuses. To examine the muscle and nerve morphology, we morphometrically and immunohistochemically examined sagittal sections of unilateral upper eyelids obtained from 21 term fetuses (approximately 30-42weeks of gestation) and, for the comparison, those from 10 midterm fetuses (12-15weeks). The approximation margin of the upper eyelid always corresponded to the entire free margin in midterm fetuses, whereas it was often (18/21) restricted in the posterior part in term fetuses. Thus, in the latter, the thickness at the approximation site to the lower lid often ranged from 0.8 to 1.6mm and corresponded to 18-56% of the nearly maximum thickness of the lid. In the lower part of the upper eyelid, a layer of the orbicularis oculi muscles often (14/21) provided posterior flexion at 90-120° to extend posteriorly. Nerve fibers running along the mediolateral axis were rich along the approximation surface at term, but they might not be reported in the upper eyelid of adults. Being different from adult morphologies, the term eyelid was much thicker than the approximation surface and it carried a flexed muscle layer and transversely-running nerve. The infrequent blinking in fetuses seemed to provide a specific condition for the muscle-nerve growth. Plastic and pediatric surgeons should pay attention to a fact that infants' upper eyelid was unlikely to be a mini-version of the adult morphology.

Role of Gubernaculum testis inervation during the process of testicular migration in human fetuses.

The gubernaculum seems to be the most important anatomical structure in the testicular migration process. The objective of this paper is to review current literature regarding the role of gubernaculum testis nerves in testicular migration. We conducted a comprehensive literature review about the gubernaculum testis innervation. A PubMed database search was performed in April 2024, focusing on gubernaculum testis and cryptorchidism and genitofemoral nerve (GFN) and calcitonin gene-related peptide (CGRP) gene. The gubernaculum has its own nerve supply, the GFN, descending on the anteromedial surface of the psoas muscle from L1-L2 segments. The second phase of testicular descent is regulated by androgens and CGRP, released from the sensory nucleus of the GFN. The GFN doesn't directly play a role in testicular migration but there is a theory that shows a regulatory function of this nerve in hormonal action during this process. The gubernaculum testis has important structural alterations during the testicular migration and the genitofemoral nerve and CGRP gene are of great importance in this process. The genitofemoral nerve provides motor innervation to the cremaster muscle and gubernaculum, which helps regulate the position of the testes within the scrotum.

Health care for women during pregnancy, childbirth and the postpartum period as well as for newborns financed from public funds

Purpose – the aim of the article is to describe health care services for women during pregnancy, childbirth and the postpartum period, including newborn care, provided in the period 2017–2021.Method – the analyses included data from the Council of Ministers’ reports on the implementation and effects of the application of the Act on Family Planning, Protection of the Human Foetus and Conditions for Termination of Pregnancy, as well as demographic data published by the Statistics Poland.Results – it was shown that in the period 2017– 2021, the number of women who received the service specified in the advice given during pregnancy decreased. However, the share of births registered as coordinated care for pregnant women I (KOC I) [pl. Koordynowana Opieka nad Ciężarną] in the total number of births increased, although ultimately they constituted a small percentage of the number of births in the country. Births carried out as KOC II/III had a higher and growing share in the number of births each year. The number of patients receiving coordinated children's care, perinatal palliative care services, and the number of pregnant participants in the Prenatal Testing Program also increased. At the same time, access to the above-mentioned services depended on the place of residence of the potential patient, since relevant service providers were available only in some voivodships, or, as in the Prenatal Testing Program, obtaining the service depended on meeting strict conditions.Conclusion – it is necessary to increase the availability of the analysed services by introducing service providers in voivodeships where they are lacking. It is also necessary to enable all interested pregnant women to participate in the Prenatal Testing Program without having to meet additional conditions.

Loss of 24-hydroxylated catabolism increases calcitriol and fibroblast growth factor 23 and alters calcium and phosphate metabolism in fetal mice.

Calcitriol circulates at low levels in normal human and rodent fetuses, in part due to increased 24-hydroxylation of calcitriol and 25-hydroxyvitamin D by 24-hydroxylase (CYP24A1). Inactivating mutations of CYP24A1 cause high postnatal levels of calcitriol and the human condition of infantile hypercalcemia type 1, but whether the fetus is disturbed by the loss of CYP24A1 is unknown. We hypothesized that loss of Cyp24a1 in fetal mice will cause high calcitriol, hypercalcemia, and increased placental calcium transport. The Cyp24a1+/- mice were mated to create pregnancies with wildtype, Cyp24a1+/-, and Cyp24a1 null fetuses. The null fetuses were hypercalcemic, modestly hypophosphatemic (compared to Cyp24a1+/- fetuses only), with 3.5-fold increased calcitriol, 4-fold increased fibroblast growth factor 23 (FGF23), and unchanged parathyroid hormone. The quantitative RT-PCR confirmed the absence of Cyp24a1 and 2-fold increases in S100g, sodium-calcium exchanger type 1, and calcium-sensing receptor in null placentas but not in fetal kidneys; these changes predicted an increase in placental calcium transport. However, placental 45Ca and 32P transport were unchanged in null fetuses. Fetal ash weight and mineral content, placental weight, crown-rump length, and skeletal morphology did not differ among the genotypes. Serum procollagen 1 intact N-terminal propeptide and bone expression of sclerostin and Blgap were reduced while calcitonin receptor was increased in nulls. In conclusion, loss of Cyp24a1 in fetal mice causes hypercalcemia, modest hypophosphatemia, and increased FGF23, but no alteration in skeletal development. Reduced incorporation of calcium into bone may contribute to the hypercalcemia without causing a detectable decrease in the skeletal mineral content. The results predict that human fetuses bearing homozygous or compound heterozygous inactivating mutations of CYP24A1 will also be hypercalcemic in utero but with normal skeletal development.

Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome.

Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21). DS is a gene dosage disorder that results in multiple phenotypes including congenital heart defects. This clinically important cardiac pathology is the result of a third copy of one or more of the approximately 230 genes on Hsa21, but the identity of the causative dosage-sensitive genes and hence mechanisms underlying this cardiac pathology remain unclear. Here, we show that hearts from human fetuses with DS and embryonic hearts from the Dp1Tyb mouse model of DS show reduced expression of mitochondrial respiration genes and cell proliferation genes. Using systematic genetic mapping, we determined that three copies of the dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1a) gene, encoding a serine/threonine protein kinase, are associated with congenital heart disease pathology. In embryos from Dp1Tyb mice, reducing Dyrk1a gene copy number from three to two reversed defects in cellular proliferation and mitochondrial respiration in cardiomyocytes and rescued heart septation defects. Increased dosage of DYRK1A protein resulted in impairment of mitochondrial function and congenital heart disease pathology in mice with DS, suggesting that DYRK1A may be a useful therapeutic target for treating this common human condition.

Quantitative study of the popliteal fossa in the human fetus.

The popliteal fossa presents an extensive diamond-shaped topographical element on the posterior aspect of the knee. With the use of classical anatomical dissection, digital image analysis of NIS Elements AR 3.0 and statistics we morphometrically analyzed the size of the popliteal fossa in human fetuses aged 17-29 weeks of gestation. Morphometric parameters of the popliteal fossa increased logarithmically with fetal age: y = -44.421 + 24.301 × ln (Age) for length of superomedial boundary, y = -41.379 + 22.777 × ln (Age) for length of superolateral boundary, y = -39.019 + 20.981 × ln (Age) for inferomedial boundary, y = -37.547 + 20.319 × ln (Age), for length of inferolateral boundary, y = -28.915 + 15.822 × ln (Age) for transverse diameter, y = -69.790 + 38.73 × ln (Age) for vertical diameter and y = -485.631 + 240.844 × ln (Age) for projection surface area. Out of the four angles of the popliteal fossa the medial one was greatest, the inferior one the smallest, while the lateral one was somewhat smaller than the medial one and approximately three times greater than the superior one, with no difference with fetal age. In terms of morphometric parameters the popliteal fossa in the human fetus displays neither male-female nor right-left differences. In the popliteal fossa, growth patterns of its four boundaries, vertical and transverse diameters, and projection surface area all follow natural logarithmic functions. All the morphometric data is considered age-specific reference intervals, which may be conducive in the diagnostics of congenital abnormalities in the human fetus.

Description of the lateral fibulotalocalcaneal ligament in fetal specimens and its potential clinical implications.

The increase in ankle sprains in children is a reflection of the greater inclusion of this population in sports. This places the calcaneofibular (CFL) and the anterior talofibular (ATFL) ligaments in focus for study. In adults, the presence of arcuate fibers extending between these two ligaments suggests the existence of a new anatomical and functional complex called the lateral fibulotalocalcaneal ligament of the ankle (LFTCL), which can be associated with the persistence of instability of the talocrural joint in ankle sprains. This study aimed to verify the presence of arciform fibers between the CFL and ATFL in human fetuses and to study the topography of the lateral ankle region. Forty matched fetal ankles aged between 28 and 38weeks, fixed in 4% formalin, were macroscopically, chemically and mesoscopically dissected and analyzed in stereoscope. The ATFL was characterized as a capsular ligament consisting of two fascicles (proximal and distal). The CFL was characterized as an extracapsular ligament. The LFTCL complex was verified in all specimens, characterized by the arcuate fibers between the ATFL and the CFL. Such results suggest that this functional unit is congenital and that it should be taken into consideration in the treatment of persistent ankle instabilities in the pediatric population.

Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition.

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

Myocardial strain assessment in the human fetus by cardiac MRI using Doppler ultrasound gating and feature tracking

ObjectivesAssessment of myocardial strain by feature tracking magnetic resonance imaging (FT-MRI) in human fetuses with and without congenital heart disease (CHD) using cardiac Doppler ultrasound (DUS) gating.MethodsA total of 43 human fetuses (gestational age 28–41 weeks) underwent dynamic cardiac MRI at 3 T. Cine balanced steady-state free-precession imaging was performed using fetal cardiac DUS gating. FT-MRI was analyzed using dedicated post-processing software. Endo- and epicardial contours were manually delineated from fetal cardiac 4-chamber views, followed by automated propagation to calculate global longitudinal strain (GLS) of the left (LV) and right ventricle (RV), LV radial strain, and LV strain rate.ResultsStrain assessment was successful in 38/43 fetuses (88%); 23 of them had postnatally confirmed diagnosis of CHD (e.g., coarctation, transposition of great arteries) and 15 were heart healthy. Five fetuses were excluded due to reduced image quality. In fetuses with CHD compared to healthy controls, median LV GLS (− 13.2% vs. − 18.9%; p < 0.007), RV GLS (− 7.9% vs. − 16.2%; p < 0.006), and LV strain rate (1.4 s−1 vs. 1.6 s−1; p < 0.003) were significantly higher (i.e., less negative). LV radial strain was without a statistically significant difference (20.7% vs. 22.6%; p = 0.1). Bivariate discriminant analysis for LV GLS and RV GLS revealed a sensitivity of 67% and specificity of 93% to differentiate between fetuses with CHD and healthy fetuses.ConclusionMyocardial strain was successfully assessed in the human fetus, performing dynamic fetal cardiac MRI with DUS gating. Our study indicates that strain parameters may allow for differentiation between fetuses with and without CHD.Clinical relevance statementMyocardial strain analysis by cardiac MRI with Doppler ultrasound gating and feature tracking may provide a new diagnostic approach for evaluation of fetal cardiac function in congenital heart disease.Key Points• MRI myocardial strain analysis has not been performed in human fetuses so far.• Myocardial strain was assessed in human fetuses using cardiac MRI with Doppler ultrasound gating.• MRI myocardial strain may provide a new diagnostic approach to evaluate fetal cardiac function.

Application of artificial neural networks to evaluate femur development in the human fetus.

The present article concentrates on an innovative analysis that was performed to assess the development of the femur in human fetuses using artificial intelligence. As a prerequisite, linear dimensions, cross-sectional surface areas and volumes of the femoral shaft primary ossification center in 47 human fetuses aged 17-30 weeks, originating from spontaneous miscarriages and preterm deliveries, were evaluated with the use of advanced imaging techniques such as computed tomography and digital image analysis. In order to ensure the data representativeness and to avoid introducing any hidden structures that may exist in the data, the entire dataset was randomized and separated into three subsets: training (50% of cases), testing (25% of cases), and validation (25% of cases). Based on the collected numerical data, an artificial neural network was devised, trained, and subject to testing in order to synchronously estimate five parameters of the femoral shaft primary ossification center, thus leveraging fundamental information such as gestational age and femur length. The findings reveal the formulated multi-layer perceptron model denoted as MLP 2-3-2-5 to exhibit robust predictive efficacy, as evidenced by the linear correlation coefficient between actual values and network outputs: R = 0.955 for the training dataset, R = 0.942 for validation, and R = 0.953 for the testing dataset. The authors have cogently demonstrated that the use of an artificial neural network to assess the growing femur in the human fetus may be a valuable tool in prenatal tests, enabling medical doctors to quickly and precisely assess the development of the fetal femur and detect potential anatomical abnormalities.

In utero exposures to perfluoroalkyl substances and the human fetal liver metabolome in Scotland: a cross-sectional study

Perfluoroalkyl and polyfluoroalkyl substances are classed as endocrine disrupting compounds but continue to be used in many products such as firefighting foams, flame retardants, utensil coatings, and waterproofing of food packaging. Perfluoroalkyl exposure aberrantly modulates lipid, metabolite, and bile acid levels, increasing susceptibility to onset and severity of metabolic diseases, such as diabetes and metabolic dysfunction-associated steatotic liver disease. To date, most studies in humans have focused on perfluoroalkyl-exposure effects in adults. In this study we aimed to show if perfluoroalkyls are present in the human fetal liver and if they have metabolic consequences for the human fetus. In this cross-sectional study, human fetal livers from elective termination of pregnancies at the Aberdeen Pregnancy Counselling Service, Aberdeen, UK, were analysed by both targeted (bile acids and perfluoroalkyl substances) and combined targeted and untargeted (lipids and polar metabolites) mass spectrometry based metabolomic analyses, as well as with RNA-Seq. Only fetuses from normally progressing pregnancies (determined at ultrasound scan before termination), terminated for non-medical reasons, from women older than 16 years, fluent in English, and between 11 and 21 weeks of gestation were collected. Women exhibiting considerable emotional distress or whose fetuses had anomalies identified at ultrasound scan were excluded. Stringent bioinformatic and statistical methods such as partial correlation network analysis, linear regression, and pathway analysis were applied to this data to investigate the association of perfluoroalkyl exposure with hepatic metabolic pathways. Fetuses included in this study were collected between Dec 2, 2004, and Oct 27, 2014. 78 fetuses were included in the study: all 78 fetuses were included in the metabolomics analysis (40 female and 38 male) and 57 fetuses were included in the RNA-Seq analysis (28 female and 29 male). Metabolites associated with perfluoroalkyl were identified in the fetal liver and these varied with gestational age. Conjugated bile acids were markedly positively associated with fetal age. 23 amino acids, fatty acids, and sugar derivatives in fetal livers were inversely associated with perfluoroalkyl exposure, and the bile acid glycolithocholic acid was markedly positively associated with all quantified perfluoroalkyl. Furthermore, 7α-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis rate, was strongly positively associated with perfluoroalkyl levels and was detectable as early as gestational week 12. Our study shows direct evidence for the in utero effects of perfluoroalkyl exposure on specific key hepatic products. Our results provide evidence that perfluoroalkyl exposure, with potential future consequences, manifests in the human fetus as early as the first trimester of gestation. Furthermore, the profiles of metabolic changes resemble those observed in perinatal perfluoroalkyl exposures. Such exposures are already linked with susceptibility, initiation, progression, and exacerbation of a wide range of metabolic diseases. UK Medical Research Council, Horizon Europe Program of the European Union, Seventh Framework Programme of the European Union, NHS Grampian Endowments grants, European Partnership for the Assessment of Risks from Chemicals, Swedish Research Council, Formas, Novo Nordisk Foundation, and the Academy of Finland.

Variation in the Formation and Branching Pattern of Brachial Plexus in the Human Foetuses: A Morphometric Cross-sectional Study

Introduction: The brachial plexus is a variable nerve plexus in its formation and branching pattern. Variations in the brachial plexus are not uncommon, and its area of supply and associations with other adjacent anatomical structures require clinical and surgical attention. Aim: To find out any anatomical variations in the formation and branching pattern of the brachial plexus in human foetuses. Materials and Methods: A morphometric prospective observational study was conducted from January 2020 to July 2022, on 30 stillborn or Intrauterine Dead (IUD) human foetuses were taken in the study. Gestation age from 28 to 40 weeks of gestation were included in the study, while those with gross anomalies or morphological anomalies of the cranium and vertebral column were excluded. The dissection includes vertical midline incision of the skin from the external occipital protuberance to the lower limit of the thoracic vertebra (T12). The skin was cut in the midline and reflected laterally. All superficial and deep muscles of the neck were dissect out to clear the cervical and thoracic parts of the vertebral column. The vertebral column was cut and opened to visualise the spinal cord and spinal nerves. Based on gestational age, the foetuses were divided into three groups: four in the first group (28-31 weeks), twelve in the second group (32- 35 weeks), and fourteen in the third group (36-40 weeks) were divided for descriptive purposes. The gender of foetuses was determined based on the external genitalia. Results: A total of 60 brachial plexuses were dissected, of which 49 (81.66%) had the usual anatomical formation of the trunks: the upper trunk formed by C5 and C6 roots, the middle trunk by the C7 root, and the lower trunk by the C8 and T1 roots. Eleven (18.34%) plexuses presented variations in trunk formation. Specifically, 8 (13.3%) brachial plexuses were of the prefix type, where the upper trunk was formed by the C5 and C6 roots with an additional contribution from the C4 root; there was inter-branch communication between C6 and C7 in one (1.7%) case; the middle and lower trunks united by C7, C8, and T1 roots formed the lower trunk in another (1.7%) case, and finally, one (1.7%) case exhibited the post-fix type. Conclusion: In this study, out of the 30 foetuses examined, 11 showed variations, which is not uncommon. The prefix type of brachial plexus is quite common among the possible variations, although anatomists and neurosurgeons cannot ignore the possibility of other variations, like post-fix type or communication between the roots of the brachial plexuses.