An investigation of the conus medullaris termination level during the period of fetal development to adulthood.

The spinal cord fills the length of the vertebral canal at the early period of intrauterine term. It is reported to extend to the level of the third lumbar vertebra at birth, because the vertebral column is growing more rapidly in the longitudinal direction than the spinal cord. The present investigation aimed to determine the changes in the termination level of conus medullaris (TLCM) from fetus to adulthood in a total of 285 individuals who had no defects in the central or peripheral nervous system, and were obtained from our Faculties of Medicine and Konya Maternity Hospital between 1992-1995. The age distribution was as follows: 36 fetuses, 20 prematures and 50 neonates, 51 children aged 1 to 7 years and 128 adults aged 15 to 68 years. In this study, for fetuses, prematures, neonates and children the TLCM was determined using ultrasonography. In addition, microdissection was used in fetuses to confirm the results obtained from the above technique. Also, magnetic resonance imaging was used in adults. During fetal life the end of the conus altered its levels from S5 to L3 vertebrae. The tip of the conus medullaris of the prematures and neonates ranged from L1 to L3 vertebrae. The tip of the conus medullaris in the children lay between the Th12 and L3 vertebrae, and in the adults it was between the Th12 and L2 vertebrae. There were slight differences between the prematures and neonates in terms of the TLCM. We concluded that there are differences in the TLCM between the age groups and therefore, especially in prematures and infants the determination of the tip of conus medullaris might be important for preventing postoperative neurological complications.     

Topography of the pelvic autonomic nerves in human fetuses between 21-29 weeks of gestation

Summary A topographical study concerning the autonomic nerves in the pelvis of human fetuses was performed by investigating 300–600 m thick sections through fetal pelves, impregnated with the epoxy resin E 12 and cut with a diamond wire-saw. In addition the inferior hypogastric plexus of a 26-week old male fetus was dissected by lateral approach. In 21–29-week old fetuses the pelvic autonomic nerves are relatively thick. Thus the nerves stand out well against surrounding structures and their topographical relationships can exactly be determined. The inferior hypogastric plexus of 21–29-week old fetuses is situated on a curved line between the rectum and the ventrally adjacent structure. It constitutes a rectangular plate, which cannot be subdivided into individual plexuses for the different pelvic organs. The fetal plexus is heavily ganglionated. Large ganglia, forming the so-called ganglion of Frankenhaeuser, are found in the female as well as in the male fetus. In the fetal pelvis the connective tissue compartments are still clearly arranged, because adipose tissue is not yet abundant. The greater part of the inferior hypogastric plexus is situated exactly at the border between a dense visceral tissue medially and a loose parietal tissue laterally. The plexus does not share a common connective tissue cover with the pelvic blood vessels. In fetuses the inferior hypogastric plexus lies in close vicinity to serveral organs, but the pelvic floor is the only region where the nerves can hardly be separated from the surrounding structures.     

Pathogenic properties of encephalomyocarditis virus isolates in swine fetuses

Summary The pathogenicity of 5 different encephalomyocarditis (EMC) virus isolates was investigated in swine fetuses following injection of each virus in utero. Laparotomies were performed on 3 pregnant sows in early mid-third (39–40 days) of gestation and on 5 sows in the late mid-third (70–72 days) of gestation, and groups of fetuses were inoculated with different viruses into the amniotic sacs. The uninoculated fetuses served as controls. Thirty-five (71.4%) of 49 infected and 1 of 26 control fetuses were grossly abnormal. Virus was recovered from 18 of 28 infected fetuses and 1 of 16 control fetuses examined. Antibody to EMC virus was detected in all of 14 fetuses infected at 70–72 days of gestation and examined 11–26 days post-infection. The fetal pathogenicity was different depending on the virus strains and the fetal age at the time of virus infection. The EMC ATCC-VR 129 virus was not pathogenic but NVSL-PR, MN-25 and MN-30 were highly pathogenic to the fetuses in both early and late mid-thirds of gestation, while NVSL-MDV was pathogenic to the fetus in early but not in late mid-third of gestation. Possible mechanisms for differences in the pathogenicity between the virus strains are discussed.     

Theoretical kidney volume versus real kidney volume: comparative evaluation in fetuses

Summary In order to present equations and normal growth curves of the theoretical kidney volume we studied 290 kidneys taken from 145 fresh human fetuses ranging in age from 13 to 36 weeks post-conception (WPC). The kidneys were evaluated in terms of greatest longitudinal length (L) superior pole width (SW), inferior pole width (IW), thickness (T) and real volume (RV). The theoretical kidney volume was calculated (ellipsoid formula: volume = length × width × thickness × 0.5236) by using SW, IW and the arithmetic mean between SW and IW. The assessment of the theoretical volume by using IW was well correlated with the real kidney volume. We found no statistically significant difference between right and left kidneys. During the second trimester (13 to 24 WPC) there was no difference in kidney volume between male and female fetuses. In the third trimester (25 to 36 WPC) male fetuses presented kidney volumes significantly greater than female fetuses. To evaluate the theoretical kidney volume in fetuses, one may use the IW, which is a quickly and easily obtained measurement. During the second trimester one may monitor the fetal kidney using equations and growth curves without taking the fetal sex into account. During the third trimester the fetal kidney volume must be evaluated using specific curves for male and female fetuses.Supported by a grant from the National Council of Scientific and Technological Development (CNPq - Brazil - 302.369/86-4/BM-FV)     

Bi-iliac distance and iliac bone position compared to the vertebral column in normal fetal development

Prenatal standards of bi-iliac width were not found in the literature based on autopsy investigations, nor was the caudo-cranial position of the ilia compared to the vertebral column. The first purpose of the present study was to establish normal standard values for the bi-iliac distance in fetal life, the second to evaluate the level of the iliac bones proportional to the ossified vertebral column. Whole body radiographs in antero-posterior projections from 98 human fetuses (36 female and 44 male fetuses, as well as 18 fetuses on which the sex had not been determined) were analyzed in the study. The fetuses derived from spontaneous or induced abortions and they were radiographed as part of the required autopsy procedure. The crown-rump-length (CRL) of the fetuses varied from 32 to 245 mm. The outer and inner bi-iliac distance was measured from the radiographs with a digital Helios slide caliper. The caudo-cranial position of the iliac bones was evaluated. The present study shows that in normal fetal development there is a continuous linear enlargement of the pelvic region in the transverse and vertical planes. The upper iliac contour stays at the level of the first sacral vertebral body, whereas the lower iliac line moves caudally. Significant differences between male and female fetuses were not found. The value of the present study is that the results can be used as reference standards in prenatal pathology.     

Variation in infanticide and parental behavior in male mice due to prior intrauterine proximity to female fetuses: Elimination by prenatal stress

When sexually-naive male mice are placed together with newborn young, some males will commit infanticide (kill the young) while others will behave parentally (retrieve the young to a nest and keep them warm). The intrauterine position of male mouse fetuses, which is recorded at Cesarean delivery, has previously been found to influence the titers of estradiol that male fetuses are exposed to in utero. In adulthood, most male mice that developed in utero between male fetuses (2 M males) behaved parentally toward young, while most males that developed in utero between female fetuses (0 M males) committed infanticide. When 0 M and 2 M males were castrated at birth and tested with young in adulthood, few males committed infanticide. But, when these same males were tested with young after 25 days of treatment with testosterone, more 0 M than 2 M males committed infanticide and more 2 M than 0 M males behaved parentally. In contrast to the above findings, more 2 M than 0 M males that were castrated when 28 days old behaved parentally without treatment with testosterone; few of the non-parental males committed infanticide, but, instead, ignored the young. Finally, stressing pregnant mice by placing them under bright lights during the last third of pregnancy eliminated the effect of developing next to female fetuses in the male offspring, and all prenatally-stressed males resembled 2 M males in their behavior toward young: most prenatally-stressed males were parental rather than infanticidal when tested with young. The significance of these findings to models of hormonal effects on sexual differentiation is discussed.     

Sexual differentiation of the urogenital system of the fetal and neonatal tammar wallaby, Macropus eugenii

In male tammar wallabies, the scrotum is the first organ to become sexually differentiated, 4–5 days before birth (day 22 of gestation). This is followed by enlargement of the gubernaculum and processus vaginalis one day before birth. However the indifferent gonad does not show any signs of testicular cord formation or androgen production until later, at around the time of birth; this is more pronounced at 2 days post-partum (p.p.), when the testis takes on a characteristic rounded appearance. Primordial germ cells proliferate throughout the testis at this time, although the testis does not become significantly heavier than the ovary until around 80 days p.p.. In females, the appearance of the mammary glands is the first sign of sexual differentiation 4–5 days before birth. The indifferent gonad first shows signs of developing an ovarian cortex and medulla 7 days after birth. The migrating germ cells are confined to the cortex, and first start to enter meiosis about 25 days after birth. The Wolffian (mesonephric) ducts are patent to the urogenital sinus in fetuses at day 21 of gestation. In the female they have started to regress by 10 days p.p. and only rudiments remain by day 25 p.p.. The Müllerian (paramesonephric) ducts develop adjacent to the cranial pole of the mesonephros at about day 25 of gestation and grow caudally to meet the urogenital sinus between days 2 and 7 p.p.. The Müllerian duct of the female develops a prominent ostium abdominale by day 9 p.p., but this structure has completely regressed in males by day 13 p.p.. The testis and ovary both migrate caudally, together with the adjacent mesonephros, at about day 10 p.p.. The ovaries remain around the level of lumbar vertebra 4 after about day 7 p.p., while the testes continue to descend. The testes enter the internal inguinal ring at about day 25 p.p., about the time that prostatic buds first appear in the urogenital sinus, and are in the inguinal canal from days 25 to 36 p.p.. They enter the scrotum at around day 36 p.p., and testicular descent is complete by days 65–72 p.p.. Melanin develops in the tunica vaginalis 72 days after birth. The overall development of the urogenital system in this marsupial is similar to that of eutherians but the sequence of events differs, with some aspects of genital differentiation preceding gonadal differentiation, apparently because they are directly controlled by X-linked genes, rather than indirectly controlled by gonadal steroids.     

Fine structural correlates of the choroid plexus of the lateral cerebral ventricle of the human fetal brain

The germinal matrix neuroepithelium and the choroidal fissure of the fetal choroid plexus commonly possess microvessels that are often poorly developed. There may be a reduction of type IV collagen that surrounds these fragile microvessels. During the first and second trimester of neural development, these microvessels are friable and can undergo intraventricular hemorrhage under a number of circumstances. Early subtle changes in the integrity of germinal matrix epithelium are not easily visualized by ultrasound. The current investigation employing scanning electron microscopy clearly defines subtle hemorrhagic events and tearing of the germinal matrix neuroepithelium in the brains of human fetuses. A 23-week-old fetus survived for 11 days but died from other causes. The choroid plexus of this fetus was compared with the choroid plexus and germinal matrix epithelium of a 22-week-old fetus that was the product of an elective termination due to severe anhydramnios of unknown origin and a 19-week-old male fetus from an elective termination. All tissues were autopsy material not requiring institutional review board approval.     

Maturation of fetal heart rate and body movement in 24-33-week-old fetuses threatening to deliver prematurely

Maturation of spontaneous cardiac and body movement behavior from 24 to 33 weeks gestational age was characterized prospectively in 168 high-risk fetuses threatening to deliver prematurely. Forty-eight, low-risk fetuses delivering as healthy full-term infants served as a comparison group. Fetuses were classified on the basis of gestational age at time of testing and newborn outcome following delivery (high-risk: premature compromised, premature healthy, term healthy infant; low-risk term healthy). In the high-risk group, the average fetal heart rate was greater and decreased over gestation from 148 to 140 bpm, regardless of outcome. In the low-risk group, it decreased from 145 to 138 bpm. In high- and low-risk groups, the average number of heart rate accelerations greater than or = 15 bpm increased over gestation from 2-3 to 8 while the average number of maternally perceived movements decreased. It was concluded that maturational changes in spontaneous fetal heart rate and maternally perceived body movements in fetuses threatening to deliver prematurely parallel those of low-risk fetuses.     

MRI辅助诊断胎儿脑积水的价值

目的探讨MRI(磁共振,magnetic resonance imaging)在胎儿脑积水的早期诊断与判断预后的价值。方法对26例产前经B超检查发现或怀疑为脑积水的胎儿(轻度25例,重度1例)进行MRI扫描,予查血染色体,生后定期复查患儿脑积水变化,并根据生长发育测量指标与贝利发育量表评价生长发育情况。结果经MRI检查,确诊轻中度脑积水23例,重度2例,正常1例,其中有4例B超疑似的轻度脑积水经MRI确诊,有1例经MRI扫描未发现脑积水;继续妊娠18例,1例因"肺发育不良"死亡,存活17例;5例在生后6月或纠正胎龄6月时经贝利小儿智力发育量表测定稍低于正常,经功能锻炼和/或药物治疗后再次贝利发育量表测定均达到正常水平,12例测定正常。结论在诊断胎儿中枢神经系统畸形时,MRI具有较高的阳性率,能准确的反映脑积水的程度,未合并其他畸形且不伴有染色体异常的单纯性轻、中度胎儿脑积水预后较好,MRI可作为胎儿脑积水产前诊断的重要补充。     

Expansion pattern of terminal air-spaces in the premature rabbit lung after tracheal deposition of surfactant

Summary The expansion pattern of the lungs of full-term and premature newborn rabbits was evaluated by direct observation of the lung surface during an inflation-deflation cycle, with particular reference to the effect of tracheal deposition of surfactant before the first breath. In non-treated premature fetuses, aeration of alveoli was initiated at an endotracheal pressure of 35 cm H₂O; the mean corresponding opening pressure was 25 cm H₂O in both full-term and surfactant-treated premature animals. The process of alveolar aeration was asynchronous in all groups but at maximal inflation pressure (35 cm H₂O) the expansion pattern was uniform in full-term and surfactant-treated premature fetuses; these animals also developed residual volume. In non-treated premature animals aeration was patchy, even at maximal inflation, and the lungs emptied at the end of deflation.This work was supported by grants from The Swedish Medical Research Council (Project No. 12X-3352)     

Localization of transthyretin-mRNA and of immunoreactive transthyretin in the human fetus

Summary Five human fetuses at mid-term (16–20 weeks) and one with a gestational age of 8 weeks were investigated. The cellular localization of transthyretin (TTR)-mRNA in different organs was demonstrated by in situ hybridization with a³⁵S-labelled, single-stranded RNA probe. Immunoreactive TTR (TTR-IR) was localized with a monoclonal antibody to TTR. In all fetuses, choroid plexus epithelial cells demonstrated intense labelling for TTR-mRNA as well as strong TTR-IR. Hepatocytes, on the other hand, showed weak in situ labelling and weak or, in some cases, non-demonstrable TTR-IR. In all mid-term fetuses, but not in the 8 week fetus, TTR-mRNA and TTR were also expressed in pancreatic endocrine A-cells. The degree of in situ labelling in these A-cells was moderate, whereas that of TTR-IR was strong. Despite negative findings for TTR-mRNA in the gut and the kidney, endocrine cells of the gut and epithelial cells of the renal proximal convoluted tubules showed TTR-IR in some of the fetuses. The investigation provides evidence for TTR synthesis in the human fetal choroid plexus, liver and endocrine pancreas. However, further studies are required to demonstrate TTR synthesis in the gut and the kidney.     

Respiratory activity of the neonatal dorsolateral pons in vitro

The lateral and medial parabrachial and the Kölliker-Fuse nuclei (NPB/KF) are well known respiratory modulating centers in adulthood, but their role in neonates is largely unknown. We examined the role of the NPB/KF using hemi-sectioned pons–brainstem–spinal cord preparations in neonatal rats. Electrical stimulation applied at various intensities and delays in relation to the onset of spontaneous inspiratory C4 bursts, evoked transient depression or termination of C4 activity. This depression/termination was greatly attenuated either after perfusion of the NMDA-receptor antagonists (MK-801 or APV) or after microinjecting MK-801 into NPB/KF. Furthermore systemic application of the GABA-A receptor antagonist bicuculline reduced NPB/KF evoked inhibition of the C4 burst. Finally, we identified inspiratory, tonic inspiratory, expiratory, and inspiratory–expiratory (I–E) neurons which was major in the recorded neurons in the NPB/KF using the whole-cell patch-clamp method. MK-801 significantly decreased the driving potential and burst duration of I–E neurons. We conclude that neonatal NPB/KF mediated inspiratory off-switch operates on similar synaptic mechanisms as an adult.     

The effect of maternal exposure to dioxin on fetal steroidogenesis in the steroidogenic organs

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposed to pregnant or lactational mother impairs the reproduction and development of the pups. The defect is a serious problem, because it is caused by TCDD at much lower doses than that needed for acute toxicity in the mother. However, the toxic mechanism underlying the defect remains to be obscure. We have previously revealed that maternal exposure to TCDD (1 microg/kg) causes a reduction in luteinizing hormone in the fetal pituitary, leading to the reduced expression of testicular steroidogenic proteins such as steroidogenic acute-regulatory protein (StAR) and cytochrome P450 (CYP) 17. In addition, we have provided evidence that such a reduction imprints defects in sexual behaviors at adulthood. In this study, we investigated TCDD effect on fetal steroidogenesis in the extra-gonadal tissues. Even when pregnant Wistar rats at gestational day (GD) 15 were orally treated with TCDD (0.25, 1 or 3 microg/kg), neither expression of StAR nor CYP17 mRNA was affected in the adrenal gland, placenta and hypothalamus of male fetuses (GD20). However, TCDD induced placental StAR (3 microg/kg) and adrenal CYP17 mRNAs (0.25 microg/kg) in female fetuses. Therefore, our study suggests that while TCDD gives damage to male fetal steroidogenesis in a testis-specific manner, the dioxin enhances the steroidogenesis of the fetal adrenal gland and placenta in females. Thus, the mechanism whereby TCDD exerts its endocrine-disrupting properties is considered to differ, at least partially, between male and female fetuses.     

Thyroidectomy and parathyroidectomy in progeny encumbered with an insufficiency of these glands in the ancestors

Summary Thyroid and parathyroid glands were studied in 134 fetuses and neonates born of thyroparathyroidectomized rats.Parathyroid and thyroid glands in such progeny were subject to destructive and dystrophic changes indicating their functional exhaustion and premature waste. In 50–60% of the progeny presenting an aggravated history of a two-fold surgical intervention in the ancestry, microscopy demonstrated the presence of hyperemia and enlargement of the parathyroid glands. Histological examination showed a marked atrophy of the parathyroid gland parenchyma and its replacement by paretically dilated vessels.(Presented by Active Member N. N. Zhukov-Verezhnikov AMN SSSR) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 5, pp. 86–89, May, 1964     

Age-Related Changes in Cadmium Content and Oxidative Modification of Proteins in Different Regions of Human Spinal Cord

A direct correlation was found between the content of oxidative protein modification products in the cervical enlargement of the spinal cord and age in humans. We revealed a considerable increase in Cd(2+) concentrations in elderly and old people and an increase in Fe(2+) concentration in old people. In the lumbosacral enlargement Cd(2+) concentration was maximum and did not vary with age. The content of oxidative protein modification products significantly increased in the lumbosacral enlargement in older adults and old people. Moreover, old people had high content of Cu(2+) in the lumbosacral enlargement. Our findings suggest that accumulation of Cd(2+) play a role in the metabolism of Cu(2+) and Fe(2+), which contributes to age-related intensification of oxidative protein modification in the spinal cord.     

Prenatal diagnosis of cystic kidney disease with ventriculomegaly: a report of six cases in two related sibships

In 2 consanguineous relationships, a Cape Verdian man fathered six fetuses (5 male) with fetal ventriculomegaly and echodense fetal kidneys as visualized by ultrasonography between 16 and 32 weeks. During prenatal monitoring, an increased alpha fetoprotein level and abnormal acetylcholinesterase were detected at amniocentesis in 5 of 6 affected fetuses. Chromosomes were normal. Five pregnancies resulted in elective termination; one child was still-born prematurely. Hydrocephalus and cystic disease of the (renal) cortico medullary areas were found. One fetus had polydactyly. The differential diagnosis and prenatal diagnosis of this presumably autosomal recessive syndrome are discussed.     

Cholecystokinin-8-like-immunoreactive fibers in rat lumbosacral autonomic regions are sexually dimorphic and altered by a reduction of androgen receptors

Cholecystokinin-8-like-immunoreactive (CCK-8-LI) fibers in laminae VII and X of the rat lumbosacral spinal cord demarcate the position of preganglionic autonomic neurons. This investigation reveals that adult male Sprague-Dawley, or King-Holtzman/Sprague-Dawley rats contain more CCK-8-LI fibers in lumbosacral laminae VII and X than adult females. Furthermore, testicular feminization mutation male rats (which lack 85-90% of their functional androgen receptors) contain fewer CCK-8-LI fibers than normal male or female rats, with the amount of CCK-8-LI being reduced to a greater extent in the sympathetic vs. the parasympathetic regions of the lumbosacral spinal cord. Thus, CCK-8-LI in testicular feminization mutation male rats has a distinctly female-like pattern. These results suggest that testosterone is a regulatory factor for CCK-8-LI fibers found in laminae VII and X of the lumbosacral spinal cord. Sexual dimorphism in lumbosacral CCK-8-LI fibers may contribute to modulating the final common pathway which differentially regulates the reproductive organs and stereotypic reproductive behavior, and may be involved with the sex differences described for pain.     

An anatomical investigation of the muscles of the pelvic outlet in Japanese giant salamander (Cryptobranchidae Megalobatrachus japonicus) with special reference to their nerve supply.

Four pelvic halves from two Japanese giant salamanders (Cryptobranchidae Megalobatrachus japonicus, one male and one female) were dissected in order to obtain detailed morphological data on the lumbosacral plexus and the muscles of the pelvic outlet. According to the positions of the passage of the metazonal nerves, the nerves can be divided into three groups: 1) the nerves passing dorsal to the caudofemoralis muscle, 2) the nerves passing between the caudofemoralis and the caudoischiadicus, 3) the nerves passing ventral to the caudoischiadicus. In consideration of the sites of origin from the lumbosacral plexus, a three-way stratificational analysis can be made, group 1 arising craniodorsal to group 2, and group 3 caudoventral to group 2. It is suggested that the three pelvic outlet muscles, the caudofemoralis, caudocruralis, and caudoischiadicus, have derived from the ventral muscles of the posterior limb, and have extended ventrocaudalwards.     

Testosterone induced mounting behavior in adult female rats born in litters of different female to male ratios

Female rats can show mounting behavior towards isosexual or heterosexual conspecifics. The present experiments were designed to study whether the prenatal presence of male fetuses would affect display of this mounting behavior in adulthood. Therefore mounting behavior, after gonadectomy and during continuous treatment with testosterone propionate (TP) was studied in female rats which were born in litters without male siblings (“all female” litters) and in litters with a variable number of male siblings. Litter composition at birth did not affect display of adult mounting behavior during protracted tests (a total of 6 tests during 8 weeks of treatment with TP). The data indicate that TP induced mounting behavior in adulthood occurs independent of the prenatal presence of male fetuses. If mounting behavior in adulthood has to be “organized” by prenatally present androgen (the current way of thinking), then the present data indicate that female rat fetuses provide themselves with these hormones. It would then seem inappropriate to judge adult mounting behavior as a sign of “masculinization” of the rat brain.