Part Of Gestation Research Articles

Frontal Lobe Growth impairment in fetuses with congenital heart disease using Ultrasound parameters; A Comparative Cross-sectional study

Introduction and the Αim: 2D and 3D biometry measures can record the increased development of the fetal brain in the later part of gestation. The objective of this study is to determine whether or not the frontal brain regions of fetuses with congenital heart disease (CHD) are smaller than those of healthy controls. Patients and Μethods: The fetal Medicine unit of the Ain Shams University Maternity Hospital carried out a comparative cross-sectional study, including 140 normal fetuses and 140 fetuses with isolated CHD evaluated between 20 and 39 gestational weeks at our fetal medicine unit in the period November 2021–September 2023 Results: Our results showed the occipito-frontal diameter (OFD) and frontal antero-posterior diameter (FAPD) utilising ultrasonography. FAPD Mean±SD: 26.53 ± 10.44, OFD Mean±SD: 89.14 ± 28.34, and FAPD/OFD Mean±SD: 0.29 ± 0.05. The OFD Mean±SD was found to be 82.18 ± 18.42, the FAPD Mean±SD to be 31.68±6.58, and the FAPD/OFD Mean±SD to be 38.70±2.15. Our results showed that 0.7% of patients exhibited anomalies related to the central nervous system, such as dilated posterior fossa, vermis = 25 mm, and aberrant posterior cranial fossa. The percentage of those with a history of CHD was 3.9%.The history of CHD showed a statistically significant difference between the research groups. When examining comorbidities, surgical history, and the relationship between the other parameters and FAPD, OFD, and FAPD/OFD, there was no statistically significant difference between the groups under investigation, except for CNS abnormalities and gestational age. Conclusion, compared to normal fetuses, fetuses with CHD had shorter FAPDs and a lower FAPD/OFD ratio. Despite the fact that different types of CHD affect hemodynamics differently, there appears to be a common deficiency in the development of the frontal cortex.

Nocardioform placentitis in a sample population of mares foaling in southeastern Pennsylvania and northeastern Maryland in 2020

Nocardioform placentitis (NP) has been associated with mid to late pregnancy loss in mares. To date, disease outbreaks have been described only in central Kentucky, although sporadic, isolated cases have been reported globally. This study describes a series of cases of NP that occurred in a sample population of 299 mares foaling in southeastern Pennsylvania and northeastern Maryland in 2020. These cases coincided with an outbreak of NP that occurred in Kentucky that same year. On farms that reported information on both normal and abnormal foalings, nocardioform organisms/DNA were isolated from 6.3% of placental samples based on aerobic culture and/or PCR. In cases with characteristic gross lesions of the chorion, 41% of cases were positive on aerobic culture and/or PCR. NP was confirmed in 16 mares that had not resided in Kentucky for breeding or any part of gestation. Characteristics of mares confirmed positive for NP, including age, gestation length, and problems during gestation are described. Standardbred mares bred by artificial insemination were less likely to be affected than Thoroughbred mares bred by natural cover. Affected mares had prolonged Stage III labor compared with normal mares. These findings suggest that regional increases in NP may occur outside of Kentucky, potentially in parallel with Kentucky outbreaks.

One or two pups - optimal reproduction strategies of common noctule females

BackgroundThe success of animal reproduction is impacted by a trade-off between energetic costs and mortality associated with immediate vs. future reproductive attempts. The reproductive strategies of European insectivorous bats differ from common mammalian standards due to the use of delayed fertilisation. Phenology of bat reproduction, including length of pregnancy, which may vary in the same species at different latitudes, between years at the same site or between individuals within a colony, is influenced by ecological conditions. To assess factors influencing the course of pregnancy, we evaluated levels of blood progesterone in 20 female common noctule bats Nyctalus noctula. The bats were individually tagged and randomly divided into two groups with different hibernation ending points (i.e. a control group vs. a treatment group with one-week longer hibernation). Following emergence from hibernation, the bats were kept in a wooden box at a stable temperature of 22 °C.ResultsThe majority of females gave birth to a single neonate (65%), but one female aborted her pups 2 days before the first successful births of other females. Based on development of progesterone concentration, we were able to define a number of different reproduction strategies, i.e. females with single offspring or twins, and females with supposed resorption of one embryo (embryonic mortality after implantation of the developing fertilised egg). Progesterone levels were much higher in females with two embryos during the first part of gestation and after birth. Progesterone levels were at their highest mid-gestation, with no difference between females carrying one or two foetuses. Length of gestation differed significantly between the two groups, with the longer hibernation (treatment) group having a roughly two-day shorter gestation period.ConclusionsFemale N. noctula are able to manipulate their litter size to balance immediate and future reproduction success. The estimated gestation length of approx. 49-days appears to be standard for N. noctula, with females optimising their thermoregulatory behaviour to keep the length of gestation as close to the standard as possible.

Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation.

We present pharmacokinetic data during pregnancy and lactation for brivaracetam, lacosamide and perampanel based on two case studies. Patient 1 used brivaracetam as monotherapy and gave birth to twins. Patient 2 used a combination of brivaracetam, lacosamide and perampanel. In both patients, serum drug concentrations were monitored throughout the pregnancies. Drug concentrations were also analysed in umbilical cord blood at birth, in serum from the offspring and in breastmilk after five days and 3-11 weeks. There were minor changes in concentration/dose-ratios for brivaracetam and lacosamide. The mean milk/serum ratios for brivaracetam and lacosamide were 0.71 and 0.83, respectively, five days and 3-5 weeks after delivery. The perampanel serum concentration increased by up to 80% in Patient 2 during the last part of gestation. The mean milk/serum-ratio for perampanel was 0.13, unchanged from five days to five weeks after delivery. Whereas serum concentrations of brivaracetam and lacosamide remained fairly stable throughout pregnancy, perampanel concentrations seemed to steadily increase towards the end. The distribution to milk was considerable for brivaracetam and lacosamide and low for perampanel. More studies on mother-infant pairs are warranted to confirm these results in larger groups.

Maternal endotoxemia induces renal collagen deposition in adult offspring: Role of NADPH oxidase/TGF-β1/MMP-2 signaling pathway

Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-β1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-β1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-β1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring.

The Association between Hypertensive Disorders of Pregnancy and Peripartum Cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a diagnosis of exclusion and a heterogeneous disorder that presents during the last month of pregnancy or the first five months postpartum. It is a rare but potentially life-threatening illness. A lot of work has been done trying to discover the causes of this condition, and several risk factors have been identified, including hypertension during pregnancy (HDP), ethnicity, advanced age, and multiple gestations. HDP affects 40% of cases of PPCM, and the strength of the association increases with increasing severity of hypertension. Among PPCM patients, there is a 1.5 times higher prevalence of HDP and a four-fold higher prevalence of preeclampsia (PE). Besides, the risk of PPCM markedly increases among women with HDP (5-21 times) compared with normotensive women. The experimental work done in animal models has provided support for the angiogenic-imbalance theory proposed regarding the association between these two conditions. The presence of the same risk factors also supports the prevalence of the coexistence of PE and PPCM. During the last part of gestation, the placenta secretes more anti-angiogenic factors, which leads to the development of both PE and PPCM. However, not all patients with HDP develop PPCM. In fact, most PPCM patients do not show any signs of HDP. Further work in these patients elucidated that there is an underlying susceptibility in some women that predisposes them to develop this condition and results in a worse prognosis as compared with those PPCM patients who have HDP. Better provision of care, genetic variations, and association with HDP have been cited as some of the factors affecting prognosis. HDP has also been found to increase the risk of other forms of cardiomyopathies in the future. A lot of work still needs to be done to uncover all the pathologic mechanisms and genetic variations involved in this disorder. More intensive and focussed research may help in developing new therapies to better manage this condition and address all of its complications.

Biodistribution of [11C]-Metformin and mRNA Expression of Placentae Metformin Transporters in the Pregnant Chinchilla.

Background While metformin is the first-line pharmacological treatment of diabetes mellitus type 2, this drug is not considered safe to use in pregnant women because of its unknown consequences for the fetus. In this study, we aimed to investigate the biodistribution of metformin in the pregnant chinchilla, a species exhibiting placental characteristics comparable with the pregnant woman. Furthermore, we aimed to investigate the expression of metformin transporters in humans and chinchillas, respectively, in order to evaluate the pregnant chinchilla as a novel animal model for the use of metformin in pregnancy. Methods Three chinchillas in the last part of gestation were injected with [11C]-metformin and scanned by PET/CT for 70 minutes to visualize the distribution. To investigate the difference in expression of placenta transporters between humans and chinchillas, PCR was performed on samples from five chinchilla placentae and seven human placentae. Results Dynamic PET with [11C]-metformin showed that the metformin distribution in chinchillas was similar to that in nonpregnant humans, with signal from kidneys, liver, bladder, and submandibular glands. Conversely, no radioactive signal was observed from the fetuses, and no metformin was accumulated in the chinchilla fetus when measuring the SUV. PCR of placental mRNA showed that the human placentae expressed OCT3, whereas the chinchilla placentae expressed OCT1. Conclusion Since metformin did not pass the placenta barrier in the pregnant chinchilla, as it is known to do in humans, we do not suggest the chinchilla as a future animal model of metformin in pregnancies.

Ecological factors affecting eruption timing of mandibular teeth in roe deer

Increasing evidence suggests that conditions in early life have important consequences for body size and fitness in mammals. As regards herbivores, teeth play a central role in the long-term performance of individuals. So far, however, patterns of teeth eruption have been scarcely investigated in relation to environmental and climatic factors experienced by herbivores. We described the eruption timing of mandibular teeth in a population of roe deer (Capreolus capreolus) located in the Apennines (Central Italy), through the analysis of 2161 jaws of fawns (1176 females and 985 males) shot in their first winter of life over three hunting seasons (2013–2015). Results showed that the percentage of juveniles exhibiting permanent teeth depends on the cohort. Among the factors that may affect both incisiviform and molariform teeth replacement timing, our findings include body mass and population density. Additional factors determining the relative speed of teeth replacement are (1) food availability for the mother during the last part of gestation, the birth period and the lactation, (2) winter temperature experienced by the mother, and (3) temperature experienced by fawns during their first summer and autumn. Besides, for the first time in literature, elevation was reported to delay front teeth replacement. A greater number of climatic factors were found to shape the eruption timing of the third molar (M3) in comparison to that of incisiviform teeth. Also, a different pattern was found in males and females. The eruption of M3 is, indeed, a costly and long-lasting process requesting optimal nutritional conditions and the meeting of a threshold jaw size. Our results indicate a strong correlation between environmental conditions and eruption process, i.e., between resource availability during the gestation and rearing periods and eruption timing.

“Check our watches”. III. Doppler ultrasonography in the second part of gestation

This article discusses issues of screening and comprehensive Doppler ultrasonography in the second part of gestation including assessment of the uterine artery, umbilical artery, fetal middle cerebral artery and ductus venosus waveforms.

The effects of leptin on plasma concentrations of prolactin, growth hormone, and melatonin vary depending on the stage of pregnancy in sheep.

The effects of hyperleptinemia and leptin resistance during gestation are unclear. Leptin, an important neuroendocrine regulator, has anorexic effects, but its interactions with other metabolic hormones during pregnancy are unclear. We examined potential roles of leptin in regulating prolactin (PRL), GH, and melatonin plasma concentrations during pregnancy in Polish Longwool ewes. Twelve estrus-synchronized ewes carrying twins after mating were randomly assigned to receive i.v. injections of saline or recombinant ovine leptin (2.5 or 5.0 µg/kg BW). Blood samples were collected (15-min intervals over 4 h) immediately before the first injection at dusk and kept under red light. Treatments were repeated at 2-wk intervals, starting before mating and continuing from days 30 to 135 of gestation. Concentrations of plasma PRL, GH, and melatonin were determined using a validated RIA. The effects of leptin on hormone plasma concentrations varied depending on pregnancy stage and leptin dose. PRL plasma concentrations were affected at most stages of pregnancy and before gestation. In non-, very early- (day 30), and late- (day 120 and 135) pregnant ewes, exogenous leptin stimulated PRL (P < 0.001) plasma concentrations, while during the second month of gestation, it decreased PRL concentrations (P < 0.01). Leptin affected GH plasma concentrations (P < 0.05) only during the first 2 mo of pregnancy, with no effects during the second part of gestation or before pregnancy. In early-pregnant ewes (day 30 and 45), leptin decreased melatonin plasma concentrations (P < 0.05), but at day 60, leptin stimulated melatonin plasma concentrations at low (P < 0.01) and high doses (P < 0.05), with no effects in ewes after 105 d of gestation. These data indicate specific pregnancy-induced endocrine adaptations to changes in energy homeostasis, supporting the hypothesis that leptin affects PRL, GH, and melatonin release during gestation.

A longitudinal study of hair cortisol concentrations in Macaca nemestrina mothers and infants.

Cortisol is a well-known glucocorticoid that can be used as a biomarker of hypothalamic-pituitary-adrenocortical activity. To explore basal cortisol physiology during pregnancy and infancy in Macaca nemestrina monkeys, hair was collected from a convenience sample of 22 healthy mother-infant dyads. Adult females were housed in pairs as part of a small breeding colony at the Washington National Primate Research Center and infants were reared in a specialized nursery. Maternal samples were collected from females during a pregnancy-detection ultrasound and immediately following labor and delivery. Infant samples were collected at birth, 20 days, 4, 6, 8, and 10 months of age. Hair cortisol concentrations (HCCs) were determined using an enzyme immunoassay in washed and ground hair samples. Like human mothers, macaque HCCs rose during pregnancy (paired t = 5.8, df = 16, P < 0.001). Maternal HCCs at pregnancy-detection (114.2 ± 12.07 picogram/milligram [pg/mg]) were highly predictive of maternal HCCs at delivery (144.8 ± 13.60 pg/mg), suggesting a trait-like quality (r = 0.90, P < 0.001). When maternal HCCs were viewed on a continuum, the absolute rise in cortisol over the course of pregnancy was significantly related to newborn HCCs (r = 0.55, P = 0.02). Infant birth HCCs (1,027.43 ± 97.95 pg/mg) were seven times higher than maternal HCCs at delivery (paired t = 19.1, df = 16, P < 0.001). Higher birth HCCs were strongly associated with larger decreases in infant hair cortisol until 6 months of postnatal age when infant HCCs converged on values indistinguishable from adults. Overall, study results demonstrate a marked degree of fetal cortisol exposure during the latter part of gestation and suggest that the rise in maternal cortisol over pregnancy may play an influential role on HCCs in the newborn.

110 BARLEY SUPPLEMENTATION AT MID-GESTATION IN BROODMARES DOES NOT AFFECT FETAL DEVELOPMENT AND IS ACCOMPANIED BY MINIMAL PLACENTAL ADAPTATIONS

Modifications of maternal environment could alter fetal growth and development through the placenta and thus health in adulthood. The developmental origins of health and disease suggest that maternal nutrition during pregnancy may affect offspring development and subsequent energy metabolism. To understand the effect of common feeding practices during gestation, 24 saddlebred mares were allocated to 1 of 2 groups: group B was supplemented twice a day with barley (B) and group F was fed only with fodder (F) between month 7 of gestation and foaling. B mares maintained an optimal body condition score through gestation, with an increase in glycaemia and insulinemia after each meal and insulin resistance in month 9 of gestation. F mares lost condition as assessed by body condition score in the last part of gestation, leading to a moderate undernutrition and a transitional increase in nonesterified fatty acid plasma concentrations. Diets had no effect on feto-placental biometry or on placental structure. In contrast, an increase in microcotyledonary vessel volume was observed in F placentas, indicating placental adaptation, possibly to increase fetomaternal exchanges. There was no overall difference in the expression of genes involved in vascularization, nutrient transfer, growth, and development between placentas from B and F mares. Nevertheless, as seen in other species, sex-specific effects of maternal nutrition were observed in placentas from female foals, with differences in the expression of endogline, kinase insert domain receptor, insulin-like growth factor 2 and insulin-like growth factor 1 receptor genes. This study demonstrates that breeding practices such as supplementation in concentrate at mid-gestation do not seem to affect fetal development. More work is ongoing to evaluate postnatal health.

Intravenous Immunoglobulin Therapy for Persistent Pemphigoid Gestationis with Steroid Induced Iatrogenic Cushing's Syndrome

Dear Editor: A 30-year-old woman developed pemphigoid gestationis (PG) after 20 weeks of gestation during her first pregnancy. Initially, she was treated with prednisone (10~30 mg/d), but she had a miscarriage in the 26th week of pregnancy. After the miscarriage, she was treated with prednisone (30~40 mg/d) and azathioprine (100 mg/d). However, her PG did not show clinical remission and new blisters continued to develop until the 12th post-partum week. Therefore, she was referred to our clinic for further treatment. She had erythematous patches, plaques and tense bullae on both the upper extremities and trunk (Fig. 1A). Histopathological examination of the skin samples showed the presence of subepidermal vesicles with perivascular lymphocytes and eosinophils (Fig. 2A, B). Direct immunofluorescence examination revealed positive, linear deposition of IgG and C3 in the basement membrane zone (Fig. 2C, D). Therefore, we confirmed the diagnosis of PG and started her on high-dose systemic corticosteroids; however, after receiving the treatment, she rapidly gained weight and developed moon face. Therefore, we performed a rapid adrenocorticotropic hormone stimulation test and measured her 24-hour urine cortisol level; on the basis of the test results, she was diagnosed with iatrogenic Cushing's syndrome. Therefore, she was started on prednisone (40~60 mg/d) and azathiprine (100 mg/d), but the symptoms persisted. After considering further treatment options, we decided to administer intravenous immunoglobulin (IVIG) therapy at a dose of 0.5 g kg-1 day-1 for 2 consecutive days. Fig. 1 (A) Large tense bullae and erythematous pruritic plaques on the arm. (B) Improved skin lesions with postinflammatory hyperpigmentation after intravenous immunoglobulin combination treatment. Fig. 2 (A) Subepidermal blister with superficial inflammatory infiltrate. (B) Superficial perivascular lymphohistiocytic infiltration, with moderate infiltration of eosinophils. Linear staining for (C) IgG, (D) C3 at the basement membrane zone. (A) H&E, ... After receiving the IVIG therapy, her skin lesions quickly subsided (Fig. 1B), so prednisone was tapered down to 10 mg/day. She was also administered a steroid at a low dose for 8 weeks for treating her Cushing's syndrome. At the follow-up after 3 months, no lesions were found on the patient. PG is a rare autoimmune-mediated blistering disease, usually occurring in the late pregnancy and immediate postpartum period. Many patients experience spontaneous resolution during the latter part of gestation only to experience a flare at the time of delivery. However, the persistence of disease activity for many years postpartum has been reported. Numerous immunosuppressive treatments have been reported for PG1. If the disease persists, treatment options are limited because they have potential side-effects, e.g. development of Cushing's syndrome, as seen in our patient. IVIG has been used to treat various autoimmune blistering diseases2. Many authors reported the use of IVIG for treating PG. The immunomodulatory actions of IVIG are mediated via several immune-mediated mechanisms, such as complement blockade and degradation, Fc receptor blockade and induction of immunomodulatory Fc receptors, inhibition of B cells, and alteration of T-cell function, cytokine modulation, and cellular migration3. IVIG therapy is relatively safe, and severe adverse events associated with the use of IVIG are rare. Headache and acute cutaneous reactions are the most common adverse effects of the therapy, while renal failure, thromboembolic events, and anaphylaxis have rarely been reported in association with IVIG therapy3. It is difficult to differentiate refractory PG from epidermolysis bullosa acquisita using only clinical, histological and direct immunofluorescence findings. Therefore, the findings of enzyme-linked immunosorbent assay and indirect immunofluorescence performed on sodium chloride-split skin are helpful in the differentiation4. We confirmed the diagnosis of PG in the case of our patient, as PG manifests itself during pregnancy, moreover, the patient achieved remission after one-cycle treatment2,3. PG is a rare disease and only 4 cases of PG treated with IVIG have been reported to date. We presented a case of persistent PG treated with IVIG combination therapy. IVIG should be considered as a therapeutic option in patients that fail to respond to conventional immunosuppressive treatment.

Rabbit morula vitrification reduces early foetal growth and increases losses throughout gestation

Several studies have extensively examined structural and biochemical damage induced by cryopreservation that may lead to loss of rabbit embryo viability, but very little information is available on alterations in growth during gestation and at gene expression level. We started our work by comparing the distribution of losses of embryo and foetal development between control and vitrified rabbit morulae. Furthermore, data on foetal sack, foetal and maternal placenta and foetus size for 10–14days of gestation were evaluated by ultrasonography. We reported that vitrification procedure causes detrimental effects on rabbit embryo and foetal development, with two major peaks of losses: one before the implantation (at day 6) and the other during the second part of gestation (after day 14). However, foetal loss may occur during the implantation process and placenta development, as there was a reduction in development of foetus produced from vitrified-warmed embryos between day 10 and 14 of gestation. For these reasons, using a recent microarray study performed in frozen–thawed rabbit embryos as a point of reference, we analysed the effects of vitrification procedure on the expression of 10 candidate genes in 6-day-old blastocysts obtained after vitrification and transfer. We observed that the relative expressions of mRNA transcripts from SCGB1A1, EMP1, ANXA3 and EGFLAM genes were significantly altered. This could help explain why a large number (29%) of vitrified embryos were successfully implanted but subsequently failed to develop to term.Further studies in subsequent embryo–foetal developmental stages, such as initiation of placenta formation, together with more sensitive high-throughput tools, should help us understand the deficiencies that hinder foetal development and identify the repairing mechanism employed by embryos to overcome vitrification effects.

Food Intake and Nutrition During Pregnancy, Lactation and Weaning in the Dam and Offspring

ContentsIn mammalian species, the connection between reproduction and nutrition is undeniable and illustrated by numerous publications: its role concerning regulation of hormonal secretions, fertility, pregnancy outcome, lactation and neonatal development indeed retains the attention of the scientific community. The interest on the influence of nutrition in dog and cat reproductive physiology is growing. Awareness on the key aspects of feeding during critical periods like pregnancy, lactation and weaning is essential to optimize the reproductive performances in these species.

Maternal corticosterone regulates nutrient allocation to fetal growth in mice

Stresses during pregnancy that increase maternal glucocorticoids reduce birth weight in several species. However, the role of natural glucocorticoids in the mother in fetal acquisition of nutrients for growth remains unknown. This study aimed to determine whether fetal growth was reduced as a consequence of altered amino acid supply when mice were given corticosterone in their drinking water for 5 day periods in mid to late pregnancy (day, D, 11-16 or D14-19). Compared to controls drinking tap water, fetal weight was always reduced by corticosterone. At D16, corticosterone had no effect on materno-fetal transfer of [(14)C]methylaminoisobutyric acid (MeAIB), although placental MeAIB accumulation and expression of the Slc38a1 and Slc38a2 transporters were increased. However, at D19, 3 days after treatment ended, materno-fetal transfer of MeAIB was increased by 37% (P < 0.04). During treatment at D19, placental accumulation and materno-fetal transfer of MeAIB were reduced by 40% (P < 0.01), although expression of Slc38a1 was again elevated. Permanent reductions in placental vascularity occurred during the earlier but not the later period of treatment. Placental Hsd11b2 expression, which regulates feto-placental glucocorticoid bioavailability, was also affected by treatment at D19 only. Maternal corticosterone concentrations inversely correlated with materno-fetal MeAIB clearance and fetal weight at D19 but not D16. On D19, weight gain of the maternal carcass was normal during corticosterone treatment but reduced in those mice treated from D11 to D16, in which corticosterone levels were lowest. Maternal corticosterone is, therefore, a physiological regulator of the amino acid supply for fetal growth via actions on placental phenotype.

Carcinogenic effects of "whole-life" exposure to inorganic arsenic in CD1 mice.

In a previously developed mouse model, arsenic exposure in utero induces tumors at multiple sites in the offspring as adults, often duplicating human targets. However, human environmental inorganic arsenic exposure occurs during the entire life span, not just part of gestation. Thus, "whole-life" inorganic arsenic carcinogenesis in mice was studied. CD1 mice were exposed to 0, 6, 12, or 24 ppm arsenic in the drinking water 2 weeks prior to breeding, during pregnancy, lactation, and after weaning through adulthood. Tumors were assessed in offspring until 2 years of age. Arsenic induced dose-related increases in lung adenocarcinoma (both sexes), hepatocellular carcinoma (both sexes), gallbladder tumors (males), and uterine carcinomas. Arsenic induced dose-related increases in ovarian tumors (including carcinomas) starting with the lowest dose. Adrenal tumors increased at all doses (both sexes). Arsenic-induced lung and liver cancers were highly enriched for cancer stem cells, consistent with prior work with skin cancers stimulated by prenatal arsenic. Reproductive tract tumors overexpressed cyclooxygenase-2 and estrogen receptor-α. Arsenic target sites were remarkably similar to prior transplacental studies, although tumors from whole-life exposure were generally more aggressive and frequent. This may indicate that arsenic-induced events in utero dictate target site in some tissues, whereas other exposure periods of arsenic enhance incidence or progression, though other factors could be at play, like cumulative dose. Whole-life arsenic exposure induced tumors at dramatically lower external doses than in utero arsenic only while more realistically duplicating human exposure.

Polyhydramnios and bone development: An unexplored relationship

Immersion of a humans and Macaca mulatta into a pool with fluid whose specific weight is equal to their specific weight cause bone demineralization. Also, in professional scuba divers, bone mineral density is reduced. Because of water immersion, the apparent weight of scuba divers represents 10% of their actual weight. The aim of this paper was to point out a previously unexplored aspect of fetal bone development in an environment lacking adequate mechanical stress on fetal bone, such as polyhydramnios. In the first part of gestation, the human fetus develops under conditions similar to neutral floating and has an apparent weight which is approximately 5% of its actual weight. During the last trimester of gestation, the fetus overgrows the intrauterine cavity and its apparent body weight is 60-80% of its actual weight. Polyhydramnios represents an excess of amniotic fluid in the uterus during gestation and it can reduce the apparent weight of the fetus to 10-20% of its actual weight. Reduction of the mechanical stress on fetal bone caused by polyhydramnios may significantly affect bone development and ossification during the last trimester of gestation. It is necessary to direct further studies towards examining bone development and mineralization in newborns from gestations complicated by polyhydramnios. A complete lack of data and studies on fetal bone development and bone mineralization in pregnancies complicated by polyhydramnios is not surprising. There is still a misleading opinion that the fetus is in weightlessness condition in the intrauterine environment throughout the second half of gestation regardless of the amount of amniotic fluid.

17 EFFECT OF A PROGESTERONE INTRAVAGINAL DEVICE ON PREGNANCY RATE IN CROSSBREED DAIRY COWS UNDER TROPICAL CONDITIONS

The objectives of these experiments were to evaluate the effect of intravaginal progesterone device on crossbreed Holstein × Carora on pregnancy rate under 2 conditions: cycling and noncycling cows. The first experiment was conducted on 135 noncycling cows (45 ± 3 days postpartum) divided in 2 groups. The first group was treated with a timed AI procedure using a progesterone device for 9 days with an eCG injection on Day 6 and estradiol benzoate after progesterone device removal followed by AI 48 h later. The second group was not treated and they were checked until they came in heat and were inseminated. The second experiment was performed on 123 cycling cows and they were divided in 2 groups. The first group was submitted to a time AI treatment similar to that in experiment 1, and the second group was not treated and they were inseminated upon heat detection. Pregnancy rate on Day 120 postpartum was recorded and pregnancy rate was compared among the different proportion of Holstein (H) × Carora (C) crossbreed cows. For the first experiment, differences (P &lt; 0.05) were observed between ¾ Carora ¼ Holstein (46.15%) compared with the other crossbreed groups (10% 7/8 H 1/8 C, 21.42% 5/8 H 3/8 C, 29.16% ½ H ½ C). In the second experiment, differences (P &lt; 0.05) were observed between ¾ Carora ¼ Holstein (57.14%) compared with the other crossbreed groups (6.66% 7/8 H 1/8 C, 30.76% 5/8 H 3/8 C, 33.33% ½ H ½ C). For the variable pregnancy rate at 120 days postpartum, significant differences (P &lt; 0.05) were observed in cycling cows (39.2%) treated with the progesterone device v. nontreated cows (21%). In noncycling cows, there were no differences between treated and nontreated cows. In conclusion, the use of progesterone device did not improve pregnancy rate in the noncycling cows, which could be related to the negative energy balance that cows undergo during the first part of gestation. However, the use of the progesterone device in cycling cows did improve the pregnancy rate compared with nontreated, cycling cows. We demonstrated that this dairy farm has a serious problem in detecting estrous, which was help by use of the progesterone device and timed AI. Also, the Carora blood included in dairy animals help them to perform better under tropical conditions and they can became pregnant much faster than animals with a high level of Holstein blood.

An interspecies comparison of placental antibody transfer: New insights into developmental toxicity testing of monoclonal antibodies

There are profound differences in maternofetal transfer of immunoglobulins between species with extensive gestational transfer of maternal immunoglobulins in primates (including humans) via the chorioallantoic placenta as well as in rabbits and guinea pigs via the inverted yolk sac splanchnopleure. In contrast, other neonatal rodents (rats and mice) receive passive immunity predominantly postnatally. This transfer is mediated principally via FcRn receptors. Therapeutic monoclonal antibodies (mAbs) are most commonly of the IgG1 subclass, which is transported most efficiently to the fetus. In all animal species used for testing developmental toxicity, fetal exposure to IgG is very low during organogenesis, but this increases during the latter half of gestation such that the neonate is born with an IgG1 concentration similar to the mother (but not rats and mice). Review of mAb developmental toxicity studies of licensed products reveals Cynomolgus monkey as the species used in the majority of the cases (10 out of 15). Pregnancy outcome data from women gestationally exposed to mAb is limited. In general, the findings are consistent with the expected low exposure during organogenesis. Guinea-pigs and rabbits are potential candidates as "alternatives" to the use of nonhuman primates as the maternofetal transfer in the last part of gestation is at a level similar in humans. Based on the pattern of placental transfer of IgG in humans, study designs that allow detection of both the indirect effects in early gestation plus the effects of direct fetal exposure in mid and late gestation are recommended for developmental toxicity of mAbs.