Second Half Of Gestation Research Articles

Fetal heart rate variability in growth restricted fetuses

Intrauterine growth restriction (IUGR) remains a major problem in perinatal medicine because of the variety of its underlying causes and the prediction of its outcome. Characteristics of heartbeat interval patterns are associated with neuro-vegetative and humoral regulatory processes. Fetal magnetocardiography allows non-invasive assessment of these processes with high precision throughout the second half of gestation. The aim of our study was the analysis of linear and non-linear parameters of fetal heart rate fluctuations to distinguish between IUGR fetuses and a cohort of normal subjects, both pre-selected from heart-rate traces representing a quiet state of activity in the third trimester of gestation.

Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins

Better understanding of the mechanisms involved in docosahexaenoic acid (DHA) transfer to the neonate may contribute to improve dietary support for infants born prematurely to mothers with placental lipid transport disorders. We studied whether DHA supplements modify the messenger RNA (mRNA) expression of placental lipid transport proteins to allow a selective transfer of DHA to the fetus. Healthy pregnant women (n = 136) received, in a double-blind randomized trial, 500 mg DHA + 150 mg eicosapentaenoic acid, 400 microg 5-methyl-tetrahydrofolic acid, 500 mg DHA + 400 microg 5-methyl-tetrahydrofolic acid, or placebo during the second half of gestation. We analyzed the fatty acid composition of maternal and cord blood phospholipids and of placenta; we quantified placental mRNA expression of fatty acid-transport protein 1 (FATP-1), FATP-4, FATP-6, fatty acid translocase, fatty acid-binding protein (FABP) plasma membrane, heart-FABP, adipocyte-FABP, and brain-FABP. The mRNA expression of the lipid carriers assayed did not differ significantly between the 4 groups. However, the mRNA expression of FATP-1 and FATP-4 in placenta was correlated with DHA in both maternal plasma and placental phospholipids, although only FATP-4 expression was significantly correlated with DHA in cord blood phospholipids. Additionally, the mRNA expression of several membrane lipid carriers was correlated with EPA and DHA in placental triacylglycerols and with EPA in placental free fatty acids. Correlation of the mRNA expression of the membrane placental proteins FATP-1 and especially of FATP-4 with maternal and cord DHA leads us to conclude that these lipid carriers are involved in placental transfer of long-chain polyunsaturated fatty acids.

Plasma pregnancy-associated glycoprotein-1 (PAG-1) concentrations during gestation in Neospora-infected dairy cows

The aim of this study was to determine whether plasma pregnancy-associated glycoprotein-1 (PAG-1) concentrations in pregnancy are affected by persistent Neospora caninum infection in dairy cows. The data analyzed were derived from 22 multiparous cows: 16 N. caninum-seropositive and 6 N. caninum-seronegative animals (used as controls). Three of the 16 seropositive cows aborted during the study period and the corresponding data were analyzed separately. Pregnancy diagnoses were performed on day 40 post-insemination by transrectal ultrasound, and by palpation per rectum on days 90, 120, 150, 180 and 210. Blood samples were collected from each animal immediately before each pregnancy diagnosis, and then at parturition or at the time of abortion detection. Plasma was tested for antibodies against N. caninum and PAG-1 concentrations were determined by radioimmunoassay. In non-aborting animals, the effects of neosporosis (seropositive versus seronegative), N. caninum antibody levels, semen providing bull, sex of the newborn, and day of gestation on PAG-1 concentrations were evaluated by GLM repeated measures analysis of variance. The effect of the gestation period (first half versus second half) on the N. caninum antibody titer was established by the Student's t-test in seropositive cows. A significant positive effect of gestation day on PAG-1 concentrations was observed (d.f. = 6; F = 12.6; P < 0.0001). For all cows, PAG-1 concentrations increased steadily during the course of gestation, with peak concentrations recorded at parturition. Neosporosis ( P = 0.493), N. caninum antibody levels ( P = 0.921), sex of the newborn ( P = 0.856) and semen providing bull ( P = 0.087) had no effect on plasma PAG-1 concentration. There was a significant 52% increase ( P < 0.0001) in N. caninum antibody titers during the second half of gestation compared to the first half. The fates of the three aborting cows were abortion on gestation day 215 in one, and fetus mummification diagnosed on gestation days 180 and 210, respectively, in the remaining two cows. A luteolytic dose of prostaglandin was applied 30 days after mummification diagnosis in these last two cows, and fetus expulsion was detected on days 215 and 250, respectively. Two of the aborted fetuses were submitted to laboratory analysis and the presence of N. caninum was confirmed by specific PCR. In the cows with a mummified fetus, PAG-1 concentrations were low or undetectable when the diagnosis was made. These findings suggest that N. caninum infection has no effect on placental function in chronically infected, cows not suffering abortion, while PAG-1 measurements in aborting animals provide a useful indication of feto-placental status.

Iron prophylaxis in pregnancy—general or individual and in which dose?

Iron is mandatory for normal fetal development, including the brain. Iron deficiency may have deleterious effects for intelligence and behavioral development. It is important to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. Iron deficiency anemia during pregnancy is a risk factor for preterm delivery and low birth weight. In the Western countries there is no consensus on iron prophylaxis to pregnant women. An adequate iron balance during pregnancy implies body iron reserves of >or=500 mg at conception. The physiologic iron requirements in the second half of gestation cannot be fulfilled solely through dietary iron. Iron supplements during gestation consistently increase serum ferritin and hemoglobin and reduce the prevalence of iron deficiency anemia. Iron has a negative influence on absorption of other divalent metals and increases oxidative stress in pregnancy, for which reason minimum effective iron dose should be advised. From a physiologic point of view, individual iron prophylaxis according to serum ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are (1) ferritin>70 microg/l: no iron supplements; (2) ferritin 30-70 microg/l: 40 mg ferrous iron daily; and (3) ferritin<30 microg/l: 80-100 mg ferrous iron daily. In controlled studies, there are no documented side effects of iron supplements below 100 mg/day. Iron supplements should be taken at bedtime or between meals to ensure optimum absorption.

Ultrasonography for pregnancy diagnosis and evaluation in queens

In the present paper, we describe the clinical utility of ultrasonography for diagnosing and evaluating pregnancy in domestic cats. Ultrasonography is a non-invasive technique that permits an accurate diagnosis of pregnancy and allows serial evaluation of the developing embryo/fetus and the extrafetal structures. The first ultrasonographic indication of pregnancy is a gestational chamber seen on day 10 after mating as a small circular anechoic structure. From day 30, it is possible to recognize different fetal organs, and between 38 and 43 days, the gender of the fetus can be determined. Measurements obtained during the second half of gestation can be used to determine fetal age and calculations can then be made that may more accurately predict the time of parturition. Further studies are needed in the queen to determine the applicability of the echo-Doppler technique used routinely in human obstetric medicine. This type of ultrasonography could potentially provide useful information about fetal health and the maturity of the placenta.

Lack of effect on rat testicular organogenesis after in utero exposure to 3-monochloropropane-1,2-diol (3-MCPD)

3-Monochloropropane-1,2-diol (3-MCPD) is a food-born contaminant known to display toxic effects on male reproduction, producing infertility in rats and humans. Using the rat as a model, we investigated whether or not testicular organogenesis, which, in the rat species, occurs during the second half of gestation, was at particular risk regarding 3-MCPD toxicity. Pregnant rats were given daily doses of 5, 10 or 25 mg/kg BW of 3-MCPD from days 11.5–18.5 postcoitum (dpc). On 19.5 dpc, testes were removed from fetuses for histological examination and testosterone analysis. Eight genes were selected among the differentiation markers of testicular cell lineages, and their expression was studied by RT-PCR. The levels of 3-MCPD and its main metabolite, β-chlorolactic acid, were assayed in fetal tissues and dam plasma. Our results show a statistically significant decrease in the mean body weight gain of pregnant rats treated with 10 and 25 mg/kg BW of 3-MCPD. Fetal testes exposed to 3-MCPD exhibited normal histology and produced testosterone at levels that were similar to controls. In addition, 3-MCPD did not alter gene expression in the fetal testes. This lack of effect occurred under conditions where 3-MCPD and β-chlorolactic acid were found to readily cross the placental barrier and diffuse throughout the fetal tissues. Our findings indicate that 3-MCPD has minimal effect on rat testicular organogenesis.

Biochemical markers of adverse pregnancy outcomes in fetal blood

Within the past decade, significant progress has been made with regard to improving maternal and newborn health. Biochemical markers in fetal blood are assessed after diagnostic cordocentesis (which was primarily collected for genetic screening), or immediately prior to fetal transfusion. Concentrations of the following diagnostic markers are measured in this study: endothelin-1, leptin, beta-2-microglobulin and the inflammatory marker IL-6. Endothelin-1 is a potent vasoconstrictor, induced by rising venous pressure and rising shear stress. Subjects involved in this study included women with anti-DRh alloimmunized pregnancies, and fetal blood sampled pre- and post-transfusions. Rapid expansion of fetal intravascular volume by intravenous transfusion of packed red blood cells with a high hematocrit enhances fetal endothelin levels. Beta-2-microglobulin is a ubiquitous cell surface protein, associated with the major histocompatibility complex. It is a potential marker of Graft-versus-Host Disease. The median concentrations of beta-2-microglobulin are significantly higher in fetuses with prior transfusions compared with non-anemic fetuses. Evaluation of fetal beta-2-microglobulin might prove useful in identifying fetuses with potentially severe Graft-versus-Host or Host-versus-Graft reaction to cell transplants. Leptin is a recently discovered circulating hormone that cord coordinates energy intake and expenditure in adults. Leptin levels in the umbilical blood positively correlate with neonatal birth weight, suggesting a role in adipose homeostasis in utero. In this study, leptin levels were measured in fetal and paired maternal plasma in the second half of gestation, in pregnancies complicated with Down syndrome and euploid pregnancies. In euploid pregnancies, fetal leptin levels were significantly lower than in corresponding maternal values, but increased across gestation. Down syndrome was associated with significantly lower fetal leptin levels. It is possible that lower fetal leptin levels could reflect the persistent immaturity of the pattern of placental peptide hormone synthesis in fetal Down syndrome. Recent evidence strongly implicates the inflammatory response to intrauterine infection in the pathogenesis of neonatal brain and lung injury. The frequency and clinical significance of systemic inflammatory responses were defined by elevated plasma interleukin- 6 concentrations in fetuses with preterm labor. A fetal plasma interleukin-6 cut-off value of 11 pg/mg was used to define the presence of a systemic inflammatory response.

Ontogeny of the human central nervous system: What is happening when?

The present paper reviews current data on the structural development of the human nervous system. Focus is on the timing of ontogenetic events in the telencephalon. Neuronal proliferation and migration especially occur during the first half of gestation; the second half of gestation is the period of the existence of the functionally important transient structure ‘subplate’ and the major period of glial cell proliferation and programmed cell death. Axon and dendrite sprouting and synapse formation bloom during the last trimester of gestation and the first postnatal year. Major part of telencephalic myelination occurs during the first year after birth. Many developmental processes, such as myelination, synapse formation and synapse elimination continue throughout childhood and adolescence. Evidence is emerging that the peak of synapse elimination occurs between puberty and the onset of adulthood. Neurotransmitter systems are present from early foetal life onwards and their pre- and perinatal development is characterized by periods of transient overexpression. The latter is for instance true for the acetylcholinergic, catecholaminergic and glutamate systems. Thus, the development of the human brain is characterized by a protracted, neatly orchestrated chain of specific ontogenetic events. The continuous changes of the nervous system have consequences for vulnerability to adverse conditions, for diagnostics and for physiotherapeutical intervention.

Genomic analysis of neuroendocrine development of fetal brain-pituitary-adrenal axis in late gestation

The present study was performed to identify the changes in genomic expression of critical components of the hypothalamus-pituitary-adrenal (HPA) axis in the second half of gestation in fetal sheep. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brain stem in fetal sheep at 80, 100, 120, 130, and 145 days of gestation and 1 and 7 days after delivery (n = 4-5/group). Using real-time RT-PCR, we measured mRNA expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), serum- and glucocorticoid-induced kinase-1 (sgk1), proopiomelanocortin (POMC), CRF, and arginine vasopressin (AVP). Both MR and GR were highly expressed in pituitary and hippocampus; in all tissues GR was more highly expressed than MR. AVP was more highly expressed than CRF in hypothalamus. MR, GR, and sgk1 expression were increased postnatally in brain stem, and sgk1 expression was increased postnatally in hypothalamus. GR expression was reduced in pituitary in term fetuses compared with younger ages. Hypothalamic CRF expression was increased at the end of gestation compared with younger ages, and AVP expression was increased in newborn lambs. Pituitary POMC was increased at 100 days of gestation compared with 80 days; hypothalamic POMC was increased at 120 days. Overall, the results demonstrate the expression of both MR and GR in brain regions important for control of the HPA axis. Decreases in expression of GR in pituitary at the end of gestation might contribute to the decreased corticosteroid negative feedback sensitivity at term in this species.

Beat‐to‐beat estimate of fetal cardiac time intervals using magnetocardiography: longitudinal charts of normality ranges and individual trends

Fetal magnetocardiography (fMCG) records fetal cardiac electro-physiological activity during the second half of gestation. We aimed at assessing normality values, related variability, and trends of fetal cardiac time intervals (fCTI) evaluated longitudinally from beat-to-beat fMCG analysis in uncomplicated pregnancies. The fMCG were recorded with multi-channel system in shielded room. FCTI were estimated on more than 2600 fetal cardiac cycles from 51 fMCG data sets of uncomplicated pregnancies. Independent component analysis (ICA) allowed reconstructing reliable fetal signals for beat-to-beat identification of fCTI (RR, P wave, PQ, PR, QT, QTc, QRS, ST, and T wave); intra-individual variability analysis and trends were calculated; reference longitudinal charts accounted for intra- and inter-individual variations and were compared with figures estimated on averaged signals. For each data set, fCTI were calculated beat-to-beat on rhythm strips of more than 50 beats (95% overall detection rate). FCTI values, variability, and trends were in good agreement with available reference figures; intervals related to P and T waves were, respectively, underestimated and overestimated with respect to those estimated on averaged signals or obtained by other research groups. Errors were reduced and individual trends could be drawn. ICA permitted the reconstruction of reliable time course of fetal cardiac signals and the beat-to-beat calculation of time intervals, and normality ranges, with smaller errors with respect to previous studies. The retrieval of fetal traces with clear morphology and the longitudinal character of the study allowed estimating individual trends and beat-to-beat characterization, impossible with cross-sectional studies on averaged beats.

Placentation in the African elephant, Loxodonta africana. IV. Growth and function of the fetal gonads

The gonads, both ovaries and testes, of 44 elephant fetuses weighing 0.09-112 kg (6.1-21.3 months gestation) were examined grossly and histologically. As in equids, elephant fetal gonads undergo a phase of marked growth and enlargement during the second half of gestation, which is more pronounced in ovaries than testes due to growth and antrum formation of numerous follicles in the former. Stromal cells undergo hypertrophy and transformation to form zones of interstitial cells that are associated with the enlarged follicles in the ovaries and in which the primitive seminiferous tubules are embedded in the testes. The interstitial cells have the capacity to synthesize 5alpha-dihydroprogesterone and other 5alpha-reduced progestagens from cholesterol and pregnenelone and the hypothesis is raised that these fetal gonadal progestagens may supplement significantly the progestagens secreted by the multiple large corpora lutea of pregnancy in the elephant.

Effects of prolactin inhibition during late gestation on the immunity of gilts and foetuses

The goal of the present study was to determine the effects of inhibiting prolactin (PRL) synthesis for three consecutive 20-d periods during the second half of gestation, on the immune status of gilts and their foetuses. Crossbred gilts were randomly assigned as controls (n = 12) or received 10 mg of bromocriptine orally three times daily from days 50 to 69 (BR50, n = 12), days 70 to 89 (BR70, n = 12), or days 90 to 109 (BR90, n = 12) of gestation. All gilts were injected subcutaneously with ovalbumin (OVA) on days 53 and 72 of gestation. Blood samples were collected on days 50, 60, 70, 90 and 109 of gestation to evaluate the antibody response. Cellular immunity, as measured by lymphocyte proliferative response and production of interferon-γ, was characterized on controls and BR50 gilts until the end of gestation. Six foetuses from five litters per treatment were selected and their thymus and spleen were excised and weighed. Splenocytes and thymocytes were assayed to characterize lymphocyte sub-populations and to evaluate splenocyte responses to mitogenic stimulation. Average spleen weight in foetuses from BR90 gilts was significantly lower (P &lt; 0.05) than that of foetuses from control or BR70 gilts. In all gilts treated with bromocriptine,percentages of CD4+ and CD8+ lymphocyte populations in foetus spleens were numerically reduced compared with those obtained in foetus from control gilts but the differences were not significant. In BR50 gilts, inhibition of PRL synthesis did not affect the proliferative response of lymphocytes to mitogenic stimulations compared with control group, but tended (P = 0.13) to increase the production of interferon-γ. A time effect showed that production of interferon-γ by leukocytes was reduced (P &lt; 0.02) on days 80 and 100 compared with days 50 and 70, regardless of bromocriptine treatment. The antibody response of gilts to OVA was not affected by bromocriptine treatments. In conclusion, inhibition of PRL synthesis by bromocriptine did not significantly affect immune response of pregnant gilts. In foetuses, although the differences between treatments were not significant, data suggest that the foetal development of immune tissues seems to be impaired by bromocriptine treatment. Key words: Bromocriptine, prolactin, immunity, pregnancy, sow

Doppler assessment of fetal aortic isthmus blood flow in two different sonographic planes during the second half of gestation

To compare the reliability of Doppler blood flow measurements of the fetal aortic isthmus (AoI) according to whether the sampling plane is obtained from the traditional longitudinal aortic arch (LAA) view or the more recently described three vessels and trachea (3VT) view of the fetal upper mediastinum. Doppler blood flow measurements of pulsatility index (PI), resistance index (RI), peak systolic (PSV), end-diastolic (EDV) and time-averaged maximum (TAMXV) velocities were performed in the AoI of 40 fetuses between 24 and 36 weeks of gestation. All measurements were sampled in two different sonographic planes of the AoI: the LAA view, at a few millimeters beyond the origin of the left subclavian artery, and the 3VT view, just before the V-shaped junction of the aortic and ductal arches. All scans were performed by the same observer. The reliability of Doppler blood flow measurements was assessed by calculating intraclass correlation coefficients (ICCs) and limits of agreement between the two different sonographic sites evaluating the AoI. Mean values of PI, RI, PSV, EDV and TAMXV were similar in the LAA and 3VT views. The PI and vascular velocities were reliably measured from both sonographic sites. ICCs for variability of measurements were 0.78, 0.63, 0.63, 0.60 and 0.55 for PI, RI, PSV, EDV and TAMXV, respectively. Limits of agreement revealed minimal disagreement between the two sites of evaluation of the AoI for all measurements. On the basis of our observations, Doppler blood flow measurements across the fetal AoI can be reliably obtained from both the 3VT and the traditional LAA sonographic views. Since the transverse upper thoracic 3VT plane is achievable in most fetal positions, Doppler study of the AoI appears to be easier than expected.

Gradients of cone differentiation and FGF expression during development of the foveal depression in macaque retina

Cones in the foveola of adult primate retina are narrower and more elongated than cones on the foveal rim, which in turn, are narrower and more elongated than those located more eccentric. This gradient of cone morphology is directly correlated with cone density and acuity. Here we investigate the hypothesis that fibroblast growth factor (FGF) signaling mediates the morphological differentiation of foveal cones--in particular, the mechanism regulating the elongation of foveal cones. We used immunoreactivity to FGF receptor (R) 4, and quantitative analysis to study cone elongation on the horizontal meridian of macaque retinae, aged between foetal day (Fd) 95 and 2.5 years postnatal (P 2.5 y). We also used in situ hybridization and immunohistochemistry to investigate the expression patterns of FGF2 and FGFR1-4 at the developing fovea, and three other sample locations on the horizontal meridian. Labeled RNA was detected using the fluorescent marker "Fast Red" (Roche) and levels of expression in cone inner segments and in the ganglion cell layer (GCL) were compared using confocal microscopy, optical densitometry, and tested for statistical significance. Our results show that morphological differentiation of cones begins near the optic disc around Fd 95, progressing toward the developing fovea up until birth, approximately. Levels of FGF2 and FGFR4 mRNAs expression are low in foveal cones, compared with cones closer to the optic disc, during this period. There is no similar gradient of FGF2 mRNA expression in the ganglion cell layer of the same sections. Maturation of foveal cones is delayed until the postnatal period. The results suggest that a wave of cone differentiation spreads from the disc region toward the developing fovea during the second half of gestation in the macaque. A gradient of expression of FGFR4 and FGF2 associated with the wave of differentiation suggests that FGF signalling mediates cone narrowing and elongation.

Ontogeny of AMPA and NMDA receptor gene expression in the developing sheep white matter and cerebral cortex

This study examined the hypothesis that the high prevalence of white matter injury in premature infants is associated with increased expression of calcium-permeable forms of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptors in pre-myelinating white matter. We characterized expression of subunits of the AMPA, and for reference, the N-methyl- d-aspartate (NMDA), glutamate receptors at 0.5, 0.65, 0.85, and term gestation in the ovine fetal white matter and cerebral cortex. There was a low expression of the critical calcium-impermeable AMPA receptor GluR2 subunit in subcortical white matter both absolutely and relative to other AMPA subunits throughout gestation. In contrast, GluR2 subunit mRNA expression fell in the cerebral cortex with increasing gestation whereas protein expression increased. These findings suggest a vulnerability of subcortical white matter to AMPA receptor-mediated calcium toxicity throughout the second half of gestation. Thus, the hypothesis that AMPA receptor-mediated glutamate toxicity contributes to brain damage in premature infants needs to be revised.

Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection1

The multidrug resistance phosphoglycoprotein ATP-binding cassette subfamily B (ABCB1) actively extrudes a range of structurally and functionally diverse xenobiotics as well as glucocorticoids. ABCB1 is present in many cancer cell types as well as in normal tissues. Although it has been localized within the mouse placenta, virtually nothing is known about its regulation. In the mouse, two genes, Abcb1a and Abcb1b, encode ABCB1. We hypothesized that there are changes in placental Abcb1a and Abcb1b gene expression and ABCB1 protein levels during pregnancy. Using in situ hybridization, we demonstrated that Abcb1b mRNA is the predominant placental isoform and that there are profound gestational changes in the expression of both Abcb1a and Abcb1b mRNA. Placentas from pregnant mice were analyzed between Embryonic Days (E) 9.5 and 19 (term approximately 19.5d). Abcb1b mRNA was detected in invading trophoblast cells by E9.5, peaked within the placental labyrinth at E12.5, and then progressively decreased toward term (P < 0.0001). Abcb1a mRNA, although lower than that of Abcb1b at midgestation, paralleled changes in Abcb1b mRNA. Changes in Abcb1 mRNA were reflected by a significant decrease in ABCB1 protein (P < 0.05). A strong correlation existed between placental Abcb1b mRNA and maternal progesterone concentrations, indicating a potential role of progesterone in regulation of placental Abcb1b mRNA. In conclusion, there are dramatic decreases in Abcb1a and Abcb1b mRNA and in ABCB1 at the maternal-fetal interface over the second half of gestation, suggesting that the fetus may become increasingly susceptible to the influences of xenobiotics and natural steroids in the maternal circulation.

Faecal steroid metabolites for non-invasive assessment of reproduction in common warthogs ( Phacochoerus africanus), red river hogs ( Potamochoerus porcus) and babirusa ( Babyrousa babyrussa)

The objectives of this study were to analyse faecal steroid metabolites in African and South East Asian pig species kept in European zoos. Species studied were the warthog ( Phacochoerus africanus), the red river hog ( Potamochoerus porcus) and the babirusa ( Babyrousa babyrussa). Faecal samples were collected 1–3 times per week from non-pregnant and pregnant captive female warthogs ( n = 9), red river hogs ( n = 7) and babirusas ( n = 5). Enzyme-immunoassays for faecal progesterone, androgen, and oestrogen metabolites, were tested for their ability to determine follicular and luteal phases. In all three species, oestrous cycles could be monitored with 20α-OH- and 20-oxo-pregnane assays. In contrast, oestrogens and androgens were not useful in characterising follicular activity during the oestrous cycle in any species. Faecal 20α-OH- and 20-oxo-pregnane values were significantly correlated. Faecal pregnane concentrations revealed species-specific differences. Luteal phase values of 20α-OH-pregnanes were considerably higher than 20-oxo-pregnanes; 20α-OH-pregnanes were in the range of 3–10 μg/g in warthogs and red river hogs, whereas concentrations were 30–200 μg/g faeces in the babirusa. Regular oestrus cycles had a length of about 35 days in all three species studied. Results indicated a seasonal influence on the occurrence of reproductive cycles in the warthog with anoestrous periods in the European summer. The red river hog was found to be a seasonal and poly oestrous breeder; oestrus cycles started by January and continued until summer. In contrast, the babirusa showed non-seasonal ovarian cyclicity. In pregnant red river hogs, progesterone metabolites were comparable to luteal phase values of the oestrous cycle during the first 3 months of gestation, but did further increase during the last month of pregnancy. Oestrogens and 17-oxo-androstanes were significantly elevated during the second half of gestation. In summary, the reproductive biology of three exotic pig species was studied using non-invasive faecal steroid analysis and these methods were used for comparative investigations of oestrous cycles, pregnancy and seasonality.

Developmental neuropathology of the second half of gestation

In this review we focus primarily on the events taking place in the second half of gestation. At second trimester end, human brain weight gain accelerates rapidly. Germinal matrix attains maximal absolute volume, only to ablate 50% over two gestational weeks. At 10 weeks of gestation interhemispheric, choroidal, and transverse fissures exist. Germinal matrix hemorrhages peak during its devolution and some of these rupture into the lateral ventricle. By 28 weeks homologous primary sulci are present, having appeared in both hemispheres at slightly different gestational ages. Secondary sulcation, during the third trimester, is hemispherically unique. Despite emphasis on neuronal vulnerability, prevalence of lesions in white matter exceeds that of gray matter and, within white matter, diffuse white matter astrocytosis prevalence exceeds that of focal necroses. Gray matter hypotensive lesions most commonly occur in the upper brainstem and thalami followed by convexity borderzone lesions causing sclerotic microgyria. White matter hypoplasia with normal gray matter volume is sometimes associated with hypomyelination.

Development of the primate area of high acuity, 3: Temporal relationships between pit formation, retinal elongation and cone packing

By establishing an avascular, highly elastic, region within the fetal area of high acuity (AHA), the developing primate eye has created a unique substrate on which the mechanical forces of intraocular pressure (IOP) and growth-induced retinal stretch (stretch) can act. We proposed (Springer & Hendrickson, 2004b) that these forces generate both the pit and high cone density found in the adult AHA. In this paper, we use quantitative measures to determine the temporal relationships between nasal and temporal retinal elongation, changes in pit depth, cone packing, and cone morphology over M. nemestrina retinal development. Retinal length increased rapidly to about 105 days postconception (dpc; Phase 1) and then elongation virtually ceased (Phase 2) until just after birth (180 dpc). Retinal elongation due to stretch resumed during Phase 3 until approximately 315 dpc (4-5 months), after which time the retina appeared mature (Phase 4). The pit appeared during the quiescent Phase 2, suggesting that IOP acts, in conjunction with molecular changes in the inner retina, on the highly elastic, avascular, AHA to generate a deep, narrow pit and causes inner retinal cellular displacements. Subsequently (Phase 3), the pit widened, became 50% shallower and central inner retinal lamina thinned slightly due to a small amount of retinal stretch occurring in the AHA. Centripetal movement of cones was minimal until just after birth when the pit reached 88% of its maximal depth. Accelerated cone packing during Phase 3 was temporally correlated with increased stretch.

Anatomical study of the proximal femur in the fetus

Two angles effectively describe the upper femur geometry: The neck shaft angle (NSA) and anteversion (AV). AV and NSA decrease from birth until they reach their adult values, but little work has focused on in-utero life. Our aim was to determine if and how AV and NSA change through the fetal life. Eighty-seven femurs from 44 formalin preserved fetuses were sampled to achieve a biometry. Correlation tests and linear regression showed that AV was highly correlated with age: AV increases during the second half of gestation. No conclusion can be given concerning NSA. It is speculated that these changes may be caused by mechanical stresses.