Late Fetus Research Articles

Effects of altered glucose supply and adiposity on expression of hypothalamic energy balance regulatory genes in late gestation growth restricted ovine fetuses

Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term = 147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H + early GH) or late gestation (H + late GH) ( n = 6/group). GH increased maternal glycemia for the duration of treatment. H and H + early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H + late GH fetuses, with 40% increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H + early GH and H + late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.

Prenatal hypoxia triggers maladaptive alterations in the heart of very late but not in late chicken embryos

Prenatal hypoxia triggers important structural and functional changes to the heart and the vasculature concomitant to the reduction in fetal growth. In the late chicken fetus (E19-E20), chronic hypoxia causes dilated cardiomyopathy as evidenced by the dilatation of the left ventricle and a reduction in ventricular wall mass. Hypoxic hearts also evidence diastolic dysfunction and decreased left ventricular ejection fractions partly due to decreased sensitivity to β-adrenergic stimulation. Earlier in development (E15), however, the heart grows disproportionately larger to hypoxia without changes in left (979±82μm vs. 962±41μm in controls) or right ventricular wall thickness (538±60μm vs. 527±34μm in controls) nor β-adrenergic density. Marked differences in the gene transcription profile were observed due to developmental age (between E15 and E19, 65 probes of 32773 transcripts in the Affymetrix chicken array) with few genes being altered by hypoxia, 5 genes at E15 and 8 genes at E19. The most remarkable transcription change at E15 was a 9.8 fold downregulation later validated by qPCR in a gene of the Embryonic Normal Stem cell family (cENS-1), a family of retroviral origin. Taken together our findings suggest that chronic hypoxia might induce adaptive changes up to E15 in development that become pathological at late developmental stages.

Maternal selenium supplementation and timing of nutrient restriction in pregnant sheep: Impacts on nutrient availability to the fetus1

To determine the effects of maternal Se intake and plane of nutrition during mid or late gestation or both on AA concentrations and metabolite concentrations in the dam and fetus, pregnant ewe lambs (n = 64) were assigned to 1 of 8 treatments arranged in a 2 × 2 × 2 factorial array: Se level [initiated at breeding; adequate (ASe; 3.05 μg/kg of BW) or high (HSe; 70.4 μg/kg of BW)] and nutritional level [100% (control; CON) or 60% (restricted; RES) of NRC recommendations] fed at different times of gestation [d 50 to 90 (mid) or d 91 to 132 (late)]. A blood sample was obtained from each ewe and fetus on d 132 of gestation and used to measure circulating concentrations of glucose, NEFA, blood urea N, and AA. The late RES ewes and their fetuses had less (P ≤ 0.03) circulating glucose compared with late CON ewes and fetuses at d 132; however, no effect (P ≥ 0.14) of diet on the fetal:maternal glucose concentration ratio was observed. Late RES ewes had a smaller (P = 0.01) fetal:maternal NEFA ratio compared with late CON ewes. Ewes fed ASe had a greater (P = 0.01) fetal:maternal blood urea N ratio compared with HSe ewes. Fetal:maternal ratios of total circulating AA, total essential AA, and total nonessential AA were each affected (P ≤ 0.03) by the combination of Se treatment and late gestation nutritional level.

Maternal undernutrition alters fat cell size distribution, but not lipogenic gene expression, in the visceral fat of the late gestation guinea pig fetus

This study investigated the development of adipose tissue in the guinea pig and the impact of maternal undernutrition on the structural and functional characteristics of perirenal adipose tissue in the dam and fetus. Date-mated guinea pigs were provided with either ad libitum feed (Control, C) or 85% of food intake per body weight of the Controls (Undernutrition, UN). Maternal (C, n = 6; UN, n = 7) perirenal adipose tissue (PAT) was collected at 60 d gestation and fetal PAT was collected at 50 d (C, n = 4) and 60 d (C, n = 8 and UN, n = 7) gestation (term, 69 d). The expression of stearoyl-CoA desaturase (SCD-1), fatty acid synthase (FAS), lipoprotein lipase (LPL), leptin and glycerol 3 phosphate dehydrogenase (G3PDH) mRNA and glucose transporters 1 and 4 (GLUT1 and GLUT4) was determined by Real Time PCR. There was no effect of maternal UN on total or relative PAT mass in the pregnant dam. There was an increase in G3PDH, but not LPL, leptin, FAS or GLUT4 mRNA expression, in UN dams compared to Controls ( P < 0.05). In the fetal guinea pig there was no effect of maternal UN on total or relative PAT mass, however, the UN fetuses had a higher percentage of larger lipid locules in their PAT compared to Controls ( P < 0.05). The expression of FAS, LPL, SCD-1, leptin, G3PDH and GLUT4 mRNA in PAT was not different between the Control and UN fetuses. These results support previous studies which have demonstrated that maternal undernutrition is associated with an increased accumulation of visceral adipose tissue in utero, and extend them by showing that maternal undernutrition results in early changes in the size distribution of lipid locules in visceral fat depots that precede changes in lipogenic gene expression.

The development of the subplate and thalamocortical connections in the human foetal brain

The aim of this review is to present clinically relevant data on prenatal development of thalamocortical connections in the human brain. The analysis is based on extensive Zagreb Neuroembryological Collection, including more than 500 prenatal human brains stained with various classical neurohistological, as well as modern histochemical and immunohistochemical methods. The connection of thalamocortical axons during the 'waiting' period with transient cortical subplate zone and subsequent synaptic engagement in the cortical plate is the main connectivity event in the late foetus and preterm infant. This connectivity is the structural substrate for the endogeneous subplate and sensory-driven circuitry generating transient electrical phenomena and may represent a transient network in the developmental history of consciousness. Findings presented in this review should be considered in the management of pain in preterm infants, in searching for the vulnerability of the subplate zone in diagnostic procedures using the in vivo MRI and in revealing the developmental origin of cognitive and mental disorders.

A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development

BackgroundThe developmental transition between the late fetus and a newborn animal is associated with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels. We tested the hypothesis that this developmental transition is associated with large coordinated changes in the transcription of skeletal muscle genes.ResultsUsing an ovine model, transcriptional profiling was performed on Longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) and two postnatal time points, one approximately 3 days postpartum and a second at 3 months of age. The developmental time course was dominated by large changes in expression of 2,471 genes during the interval between late fetal development (120 d fetal development) and 1-3 days postpartum. Analysis of the functions of genes that were uniquely up-regulated in this interval showed strong enrichment for oxidative metabolism and the tricarboxylic acid cycle indicating enhanced mitochondrial activity. Histological examination of tissues from these developmental time points directly confirmed a marked increase in mitochondrial activity between the late fetal and early postnatal samples. The promoters of genes that were up-regulated during this fetal to neonatal transition were enriched for estrogen receptor 1 and estrogen related receptor alpha cis-regulatory motifs. The genes down-regulated during this interval highlighted de-emphasis of an array of functions including Wnt signaling, cell adhesion and differentiation. There were also changes in gene expression prior to this late fetal - postnatal transition and between the two postnatal time points. The former genes were enriched for functions involving the extracellular matrix and immune response while the latter principally involved functions associated with transcriptional regulation of metabolic processes.ConclusionsIt is concluded that during late skeletal muscle development there are substantial and coordinated changes in the transcription of a large number of genes many of which are probably triggered by increased estrogen levels. These changes probably underpin the adaption of muscle to new physiological demands in the postnatal environment.

The role of fetal autopsy and placental examination in the causes of fetal death: a retrospective study of 132 cases of stillbirths

To investigate the most plausible cause of stillbirth by evaluating clinical records and postmortem examination findings including placental analysis. A retrospective cohort study concerning 132 stillbirths from 124 pregnancies occurred in the Mother-Infant Department of the University Hospital of Modena, Italy, from January 2000 to December 2004. Collected data were reviewed and classified according to the Gardosi ReCoDe system. A reasonable cause of fetal death was identified in 99/124 pregnancies (79.84%). No associated relevant factors were disclosed in 25 fetuses (20.16%) classified as unexplained stillbirths. A succeeding scrupulous analysis of the placenta and an accurate clinical record review were useful to detect other conditions in 82 cases, including 5 cases of unexplained stillbirth. The major relevant conditions associated to stillbirths were feto-placental infection especially in the early fetal gestation age, under the 24th week of gestation, and placental insufficiency occurred both in early and late gestation age fetuses and mainly associated with a IUGR (<10th customized percentile). The main frequent secondary conditions were represented by placental anomalies including cluster of avascular villi with stromal fibrosis associated to thrombosis in minor and/or major vessel(s). Through the further analysis of the placenta, we were able to reduce the unexplained stillbirth rate from 20.16 to 15%. Accurate fetal autopsy and placental examination related to meticulous clinical collecting data are requisites in the valuation of stillbirth and could play an important role in reduction of unexplained stillbirth rate.

The relation of S100beta and metabolic and endocrine responses to acute fetal hypoxemia

Elevations in S100beta protein in umbilical cord blood have been proposed as a reproducible marker of fetal stress, leading to cell damage within the central nervous system. However, it remains unknown whether fetal S100beta concentrations correlate with established endocrine and metabolic indices of fetal distress. Hence, in the late gestation ovine fetus, plasma concentrations of S100beta, adrenocorticotropic hormone (ACTH), cortisol, neuropeptide Y (NPY), and catecholamines and blood concentrations of glucose and lactate were measured during acute hypoxemia. Under general anesthesia, 5 sheep fetuses were chronically instrumented with catheters and subjected 5 days later to 1h normoxia, 0.5h hypoxemia and 1h recovery. Plasma samples were taken during each experimental period. Hypoxemia induced significant falls in PaO2 with increases in fetal plasma concentrations of ACTH, cortisol, catecholamines and NPY, and elevations in blood glucose and lactate, all of which showed significant positive relationships with fetal plasma S100beta concentrations. Hence, evaluation of S100beta may provide a valuable clinical tool in the assessment of fetal well-being in suspected complicated pregnancies.

The ovine sexually dimorphic nucleus, aromatase, and sexual partner preferences in sheep

We are using the domestic ram as an experimental model to examine the role of aromatase in the development of sexual partner preferences. This interest has arisen because of the observation that as many as 8% of domestic rams are sexually attracted to other rams (male-oriented) in contrast to the majority of rams that are attracted to estrous ewes (female-oriented). Our findings demonstrate that aromatase expression is enriched in a cluster of neurons in the medial preoptic nucleus called the ovine sexually dimorphic nucleus (oSDN). The size of the oSDN is associated with a ram's sexual partner preference, such that the nucleus is 2–3 times larger in rams that are attracted to females (female-oriented) than in rams that are attracted to other rams (male-oriented). Moreover, the volume of the oSDN in male-oriented rams is similar to the volume in ewes. These volume differences are not influenced by adult concentrations of serum testosterone. Instead, we found that the oSDN is already present in late gestation lamb fetuses (∼day 135 of gestation) when it is ∼2-fold greater in males than in females. Exposure of genetic female fetuses to exogenous testosterone during the critical period for sexual differentiation masculinizes oSDN volume and aromatase expression when examined subsequently on day 135. The demonstration that the oSDN is organized prenatally by testosterone exposure suggests that the brain of the male-oriented ram may be under-androgenized during development.

OP04.04: The myocardial performance (Tei) index is more reliable than shortening fraction (LVSF) in early late trimester fetuses for determining ventricular function

M. Habli2,3, J. F. Cnota1, A. Divanovic1, T. M. Crombleholme3, M. Kinsel-Ziter1, R. Keller1, E. C. Michelfelder1 1Fetal Heart Program, The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 2Division of Maternal Fetal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA; 3Fetal Care Center of Cincinnati, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

New insight into the bony labyrinth: A microcomputed tomography study

Objectives To visualize and quantify the morphology and mineralization of the developing fetal human bony labyrinth, using 3D-microcomputed tomography (3D-μCT) imaging. Methods Eleven right temporal bones from late second and third trimester fetuses were used in this prospective pilot study. After fixation in 10% formalin solution, all samples underwent a microcomputed tomography (μCT) scan, permitting the 3D imaging of the bony labyrinth as well as the quantitative assessment of mineral density, angular distances and dimensions of inner ear components the progression of ossification was precised with histological observations. Results Our findings show different rates of growth among the semicircular canals, the vestibular aqueduct, the oval window, the round window and the cochlea. The final sizes of the cochlea and round window are achieved at 23 weeks of gestation, with heights of 5 mm and 2 mm, respectively. The oval window reaches adult size at 35 weeks, whereas the vestibular aqueduct will attain adult size after birth. An increasing degree of torsion of each semicircular canal is observed during fetal development. The superior semicircular canal achieves adult size at 24 weeks, before the posterior and the lateral canals (25 weeks). The time-course of ossification and mineralization observed in structures and confirmed by histology. Conclusions During this developmental period poorly studied until now, our findings suggest that each part of the bony labyrinth follows distinct growth and ossification kinetics trajectories, some of these reaching their adult size only after birth.

Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

Old World monkeys provide naturally occurring and experimentally induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia and increased incidence of type 2 diabetes that characterize early gestation-exposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health-care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood.

Levels of mRNA for three selenoproteins in skeletal muscle of fetal and newborn pigs

Selenoproteins have wide-ranging functions throughout the body, including important roles in protection against oxidative stress, as well as muscle development and integrity. In this study, prepubertal gilts were randomly assigned to either a Se-sufficient or deficient diet ( n = 12/treatment). Levels of mRNA coding for the selenoproteins glutathione peroxidase-1 (GPx-1), selenoprotein W (SelW) and selenoprotein N (SelN) and the concentration of Se in fetal and neonatal swine skeletal muscle ( gluteus maximus) were measured at time intervals throughout gestation and immediately after birth. Total RNA was isolated from skeletal muscle, and cDNA was synthesized for real-time RT-PCR analysis of the selected selenoproteins. Selenium concentration in skeletal muscle of fetal and newborn pigs decreased throughout gestation ( P < 0.0001) and was lower ( P < 0.05) when dams were fed the low Se diet. Levels of GPx-1 mRNA in fetal skeletal muscle were unaffected by maternal Se intake nor did GPx-1 mRNA levels change during late gestation. Selenoprotein W mRNA levels increased ( P = 0.01) in fetal skeletal muscle during late gestation but were reduced ( P = 0.05) by low maternal intake of Se. Levels of SelN mRNA showed a gestational time by treatment interaction ( P < 0.05). The increased levels of SelW mRNA in skeletal muscle during late gestation, despite a decrease in Se concentration, indicate that SelW may be an important antioxidant protein to the late term fetus and the newborn.

Histomorphology and proteomics analysis of human fetus liver

To investigate the histomorphology and protein expression profiles of human fetal liver at different developmental stages. The protein expression patterns of human fetus livers at early and late stages were profiled by two-dimensional gel electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The differentially expressed proteins were identified by searching the protein databases with Mascot or ProFound softwares. The obvious differences between early and late fetus liver were not only in morphology but also in protein expression profiles. Compared with protein expression pattern of hepatocellular carcinoma, 32 differential or similar protein spots were analyzed by MALDI-TOF MS, and 26 proteins, including proteins involved in cell proliferation, apoptosis and metabolism, were identified. The data suggest that the hepatic cancer cells regain some characteristics of fetal hepatic cells during the process of carcinogenesis.

Branched Chain Fatty Acids Are Constituents of the Normal Healthy Newborn Gastrointestinal Tract

Vernix suspended in amniotic fluid is normally swallowed by the late term fetus. We hypothesized that branched chain fatty acids (BCFA), long known to be major vernix components, would be found in meconium and that the profiles would differ systematically. Vernix and meconium were collected from term newborns and analyzed. BCFA-containing lipids constituted about 12% of vernix dry weight, and were predominantly saturated, and had 11-26 carbons per BCFA. In contrast, meconium BCFA had 16-26 carbons, and were about 1% of dry weight. Meconium BCFA were mostly in the iso-configuration, whereas vernix BCFA contained dimethyl and middle chain branching, and five anteiso-BCFA. The mass of BCFA entering the fetal gut as swallowed vernix particles is estimated to be 180 mg in the last month of gestation whereas the total mass of BCFA found in meconium is estimated to be 16 mg, thus most BCFA disappear from the fetal gut. The BCFA profiles of vernix and meconium show that BCFA are major components of normal healthy term newborn gastrointestinal tract. BCFA are candidates for agents that play a role in gut colonization and should be considered a nutritional component for the fetus/newborn.

Placental transfer and pharmacokinetics of allopurinol in late pregnant sows and their fetuses

At present no standard pharmacological intervention strategy is available to reduce these adverse effects of birth asphyxia. In the present study we aimed to evaluate placental transfer of allopurinol, an inhibitor of XOR. For this purpose, fetal catheterization of the jugular vein was conducted in five late pregnant sows (one fetus per sow). At 24-48 h after surgery, sows received allopurinol (15 mg/kg body weight; i.v.) and pharmacokinetics of allopurinol and its active metabolite oxypurinol were measured in both late pregnant sows and fetuses. Maternal and fetal blood samples were collected during and after allopurinol administration. Maternal C(max) values averaged 41.90 microg/mL (allopurinol) and 3.68 microg/mL (oxypurinol). Allopurinol crossed the placental barrier as shown by the average fetal C(max) values of 5.05 microg/mL at 1.47 h after allopurinol administration to the sow. In only one fetus low plasma oxypurinol concentrations were found. Incubations of subcellular hepatic fractions of sows and 24-h-old piglets confirmed that allopurinol could be metabolized into oxypurinol. In conclusion, we demonstrated that allopurinol can cross the placental barrier, a prerequisite for further studies evaluating the use of allopurinol as a neuroprotective agent to reduce the adverse effects following birth asphyxia in neonatal piglets.

The temporal requirement for vitamin A in the developing eye: Mechanism of action in optic fissure closure and new roles for the vitamin in regulating cell proliferation and adhesion in the embryonic retina

Mammalian eye development requires vitamin A (retinol, ROL). The role of vitamin A at specific times during eye development was studied in rat fetuses made vitamin A deficient (VAD) after embryonic day (E) 10.5 (late VAD). The optic fissure does not close in late VAD embryos, and severe folding and collapse of the retina is observed at E18.5. Pitx2, a gene required for normal optic fissure closure, is dramatically downregulated in the periocular mesenchyme in late VAD embryos, and dissolution of the basal lamina does not occur at the optic fissure margin. The addition of ROL to late VAD embryos by E12.5 restores Pitx2 expression, supports dissolution of the basal lamina, and prevents coloboma, whereas supplementation at E13.5 does not. Surprisingly, ROL given as late as E13.5 completely prevents folding of the retina despite the presence of an open fetal fissure, showing that coloboma and retinal folding represent distinct VAD-dependent defects. Retinal folding due to VAD is preceded by an overall reduction in the percentage of cyclin D1 positive cells in the developing retina, (initially resulting in retinal thinning), as well as a dramatic reduction in the cell adhesion-related molecules, N-cadherin and β-catenin. Reduction of retinal cell number combined with a loss of the normal cell–cell adhesion proteins may contribute to the collapse and folding of the retina that occurs in late VAD fetuses.

The effect of rapamycin on DNA synthesis in multiple tissues from late gestation fetal and postnatal rats

Rapamycin is a potent antiproliferative agent that arrests cells in the G1 phase of the cell cycle through a variety of mechanisms involving the inhibition of the mammalian target of rapamycin (mTOR) pathway. The majority of normal cells in culture are sensitive to the cytostatic effects of rapamycin, whereas the growth of many malignant cells and tumors is rapamycin resistant. We had shown previously that hepatic DNA synthesis in the late gestation rat fetus is rapamycin resistant even though signaling through the mTOR/S6 kinase (S6K) pathway is attenuated. On the basis of this finding, we went on to characterize the response to rapamycin in a spectrum of tissues during late gestation and the early postnatal period in the rat. We found that rapamycin had no effect on DNA synthesis in major organs such as heart, intestine, and kidney in the fetal and early postnatal rat despite a marked attenuation in the phosphorylation of ribosomal protein S6. In contrast, the proliferation of mature hepatocytes during liver regeneration was highly sensitive to rapamycin. These data indicate that basal cellular proliferation in a wide variety of tissues is rapamycin resistant and occurs independently of mTOR/S6K signaling. Furthermore, the well-characterized effects of rapamycin in tissue culture systems are not recapitulated in the asynchronous cell proliferation that accompanies normal growth and tissue remodeling.

Effect of Variable Long-Term Maternal Feed Allowance on the Development of the Ovine Placenta and Fetus

Maternal feed allowance during pregnancy can affect the development of the ovine placenta and fetus. The impact of variations in feed allowance prior to as well as throughout pregnancy has received less attention. Ewes were offered 0.6 (R), 1.2 (C) or 1.8 (AL) maintenance requirements from 89 days before conception until day 133 of pregnancy. Ewes were euthanased on days 50, 92 and 133 of pregnancy. Ewe live weight and body condition score, maternal and fetal metabolic and hormonal profiles, fetal body dimensions and organ weights, and the number, weight and morphology of placentomes were measured. Maternal live weight and condition score were lower in R compared to AL ewes at all stages of pregnancy ( P < 0.05). Plasma glucose and albumin concentrations of R ewes were significantly reduced ( P < 0.05) at mid and late gestation, respectively. Placental components were generally unresponsive to long term variations in maternal feed allowance. However, placental weight was significantly ( P < 0.05) correlated with fetal weight at days 50 ( r = 0.59) and 133 ( r = 0.69) of gestation. By late gestation growth-retarded singleton fetuses from R ewes were 19% lighter ( P < 0.05), with reduced abdominal (9%) and thoracic (10%) girths ( P<0.05) but of similar crown-rump length compared with fetuses from AL ewes. These differences were associated with significantly reduced IGF-I concentrations in fetal plasma ( P < 0.05). In conclusion, maternal, placental and fetal adaptations to long established planes of variable maternal feed allowance were able to maintain fetal growth during early and mid-pregnancy while fetal growth restriction, associated with reduced fetal IGF-I levels, became apparent in late pregnancy.

Fetal insulin secretion in late gestation: does size matter?

Fetal insulin secretion in late gestation: does size matter?