Sonographic biometrical normograms and estimation of fetal weight in the baboon (Papio anubis)

Background  In order to consider the non-human primate as an adequate model for studying prenatal diagnosis and therapy, comparative data on fetal growth should be available.
Methods  Sixty ultrasound scans were performed in 22 baboons between 14 and 167 days of gestation. Measurements included greatest length, head circumference, biparietal diameter (BPD), transcerebellar diameter, abdominal circumference (AC), femur length (FL), and amniotic fluid index. For all parameters growth curves were established and compared with human curves. In 18 animals, birth weight and placental weight were determined. Different equations described in the literature for estimating the human fetal weight were tested in the baboon.
Results  The fetal and placental growth pattern in the baboon was comparable with humans. The best predictor of fetal weight was the formula presented by Combs: 0.23966 × AC² × FL + 1.623 × BPD³.
Conclusions  A high similarity between baboon and human growth charts is shown. The best equation for estimating the baboon fetal weight is proposed.     

Study of prenatal growth in the capuchin monkey (Cebus apella) by ultrasound

Capuchin monkey (Cebus apella) is a new world primate that in recent years has become important in biomedical research. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in capuchin monkeys. In seven pregnant animals serial ultrasonic assessment of gestational sac (GS), embryo/fetal greatest length (GL), biparietal diameter (BPD), thorax height (TH), and femur length (FL) were performed. Identification of the GS was possible on day 23+/-2.8 (X +/- SE). The embryo and its heartbeat was detected on day 32.7+/-2.8, the GL being measurable thereafter. By day 45.4+/-1.4 BPD and TH were measurable. FL could only be measured from day 70.6+/-2.1. Predictive regression equations of gestational age (GA) were modeled with data obtained. In addition, preliminary data of fetal heart rate showed a decrease in frequency with advancing gestation.     

采用三次样条拟合胎儿体格发育指标百分位数参考值

目的:生长发育评价标准的最佳形式是年龄别百分位数,然而,目前我国缺乏胎儿的孕周别体格发育指标百分位数评价标准,影响了胎儿宫内生长发育水平的准确评价,本研究拟建立陕西省正常单胎妊娠孕妇胎儿体格发育指标百分位数参考标准。方法:以陕西省西安、汉中、延安5所大型综合医院超声科或妇产科超声室为数据采集点,选择2010-01-01到2010-12-31间进行常规孕期检查的正常单胎妊娠胎儿的超声测量数据,随机抽取一次测量结果,共收集到6832个单胎正常妊娠胎儿的超声测量数据。采用三次样条法对陕西省孕16-41周正常单胎妊娠胎儿的双顶径、腹围、股骨长百分位数进行拟合。结果:三次样条拟合胎儿的双顶径、腹围、股骨长百分位数,各百分位数的决定系数均在0.95以上,均方差均在各指标重复测量的容许误差内,拟合结果满意。计算出了胎儿的孕周别双顶径、腹围、股骨长的P3、P10、P25、P50、P75、P90、P97百分位数。结论:三次样条兼顾了曲线拟合中的拟合优度和光滑度,能更好的实现曲线拟合的目的。所建立的孕周别胎儿体格发育指标百分位数符合胎儿宫内生长发育规律,为胎儿宫内生长发育的准确评价提供了科学、准确的评价工具,可用于产科临床和研究工作中。     

Teratogenic effects of nicotine on palate formation in mice

Fetuses of pregnant CD-1 mice, exposed to intraperitoneal injection of 0.1% nicotine sulfate at a dose of 1.67 mg/kg body weight/day on gestational days 6-15, were compared with control (saline injected and non-injected) fetuses to assess the effects of nicotine on fetal growth in general and palatogenesis in particular. A total of 59 pregnant females (18 experimental and 41 control) were sacrificed on the 18 th gestational day and their fetuses were examined gross morphologically and histologically (using serial sections through the head in the frontal plane). Data analysis revealed that maternal weight gain, crown-rump length, fetal weight and head dimensions were significantly reduced in nicoted treated animals when compared to those of the controls. Histological examination revealed that 9.6% of fetuses of nicotine injected mothers presented clefts of the palate, whereas none of the control fetuses had that anomaly. It was concluded that nicotine has a detrimental effect on general growth and development as well as on palatogenesis of mice.     

Effects of gestational age and labor on the expression of prostanoid receptor genes in pregnant baboon cervix

We sought to determine whether expression of genes encoding prostaglandin receptors varied with advancing gestational age and in association with the onset of spontaneous labor in the cervix of pregnant baboons. We performed cesarean hysterectomy on 14 pregnant baboons, five during spontaneous labor. Expression of genes was quantified by Northern analysis. Clear signals which were similar in estimated size to the human genes were detected by Northern analysis for the genes encoding the EP1, EP2, EP3, EP4, FP, IP and TP receptors. Expression of the gene encoding the prostanoid EP1 receptor increased with advancing gestational age prior to labor (r2 = 0.8, P = 0.007). There was a 4 fold lower level of expression of the EP2 receptor gene among animals in labor compared with animals not in labor (P = 0.006) and approximately 2-fold lower levels of expression of the FP and TP receptor genes (P < 0.0001 and P = 0.0002, respectively). We conclude that variation in the relative expression of prostanoid receptor types and sub-types may have a role in cervical dilatation in primate parturition.     

Fetal blood sampling in baboons (Papio spp.): Important procedural aspects and literature review

Background  The baboons ( Papio cynocephalus ) have similarities with human placentation and fetal development. Fetal blood sampling allows investigators to assess fetal condition at a specific point in gestation as well as transplacental transfer of medications. Unfortunately, assessing fetal status during gestation has been difficult and fetal instrumentation associated with high rate of pregnancy loss. Our objectives are to describe the technique of ultrasound guided cordocentesis (UGC) in baboons, report post-procedural outcomes, and review existing publications.
Methods  This is a procedural paper describing the technique of UGC in baboons. After confirming pregnancy and gestational age via ultrasound, animals participating in approved research protocols that required fetal assessment underwent UGC.
Results  We successfully performed UGC in four animals (five samples) using this technique. Animals were sampled in the second and third trimesters with fetal blood sampling achieved by sampling a free cord loop, placental cord insertion site or the intrahepatic umbilical vein. All procedures were without complication and these animals delivered at term.
Conclusions  Ultrasound guided fetal umbilical cord venipuncture is a useful and safe technique to sample the fetal circulation with minimal risk to the fetus or mother. We believe this technique could be used for repeated fetal venous blood sampling in the baboons.     

Real-time ultrasonic evaluation of the baboon pregnancy: biometric measurements

Ultrasonic and direct biometric measurements of nine fetal baboons were made during 23 evaluations. Both the femur length and the biparietal diameter were correlated to gestational age. These initial results have facilitated intrauterine surgery. The data presented will help in determining adequate fetal growth and in dating the baboon pregnancy.     

Transabdominal Ultrasound for Pregnancy Diagnosis in Reeves' Muntjac Deer

Reeves'' muntjac deer (Muntiacus reevesi) are a small cervid species native to southeast Asia, and are currently being investigated as a potential model of prion disease transmission and pathogenesis. Vertical transmission is an area of interest among researchers studying infectious diseases, including prion disease, and these investigations require efficient methods for evaluating the effects of maternal infection on reproductive performance. Ultrasonographic examination is a well-established tool for diagnosing pregnancy and assessing fetal health in many animal species^1-7, including several species of farmed cervids^8-19, however this technique has not been described in Reeves'' muntjac deer. Here we describe the application of transabdominal ultrasound to detect pregnancy in muntjac does and to evaluate fetal growth and development throughout the gestational period. Using this procedure, pregnant animals were identified as early as 35 days following doe-buck pairing and this was an effective means to safely monitor the pregnancy at regular intervals. Future goals of this work will include establishing normal fetal measurement references for estimation of gestational age, determining sensitivity and specificity of the technique for diagnosing pregnancy at various stages of gestation, and identifying variations in fetal growth and development under different experimental conditions.     

Teratological studies of prenatal exposure of mice to a 20 kHz sawtooth magnetic field

In order to evaluate the importance of gestational age in possible effects due to exposure to a 20 kHz sawtooth magnetic field, pregnant ICR mice at gestational 2.5-15.5 days post-coitus, which is the most sensitive stage for the induction of major congenital malformations, were exposed in a carrousel irradiator. The mice were exposed to a 20 kHz intermediate frequency (IF) sawtooth magnetic field had a 6.5 microT peak intensity for 8 h/day. The animals were sacrificed on the 18th day of gestation; and the fetuses were examined for mortality, growth retardation, changes in head size, and other morphological abnormalities. From the above conditions, it is concluded that the exposure to a 20 kHz sawtooth magnetic field with 6.5 microT peak intensity does not inflict any adverse effect on fetuses of pregnant mice.     

Prenatal growth in the cynomolgus and rhesus macaque (Macaca fascicularis and Macaca mulatta): A comparison by ultrasonography

The rhesus monkey has played an important role in the history of reproductive research. Because of limitations on the exportation and availability of this species, several other species of nonhuman primates have been considered as alternate models. Among them is the crab-eating, or cynomolgus, macaque (Macaca fascicularis), which displays similarities in developmental, reproductive, and physiological parameters. The use of both species of macaques for pregnancy-related studies necessitates the assessment of differences in growth and development through gestation. Observations during the embryonic and fetal periods in both species have been compared with diagnostic ultrasound. Results indicate no significant differences in size during the embryonic and early fetal periods, but a greater acceleration of growth in the rhesus begins at approximately 100–110 gestational days (GD). Analysis of embryonic and fetal heart rates indicate no differences between the two species. Normal predictive values for a variety of growth parameters including gestational sac, greatest length, biparietal diameter, and femur length have boon calculated by multiple regression analysis. These charts have proven useful for confirming the gestational age after timed matings and for predicting the age of animals for which the conception date is not known.     

Cellular and biochemical aspects of growth retardation in rat fetuses induced by maternal administration of selected anticancer agents.

Single ip injections of 600 mg/kg 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DIC) and 900 mg/kg 5-[3,3-bis(2-chlorethyl)-1-triazeno]-imidazole-4-carboxamide (BIC) were given to pregnant Wistar rats at day 12 and the animals were killed 4 h after injection and at days 13-17 of gestation. Fetal tissues were used to determine total DNA, RNA, and protein and the data used to derive cell number and cell weight, RNA, and protein/cell. Both compounds reduced total fetal body weight, DNA, RNA, and protein but reduction of RNA by BIC was not statistically significant. These effects were observed 4 h after injection, increased with age (days 13-17), and were 3-4 times greater for DIC than BIC. By using the value of 6.2 mumug DNA/cell, cell number and per-cell values for weight, RNA, and protein, and weight: DNA, RNA:DNA, and protein:DNA ratios were computed. The per-cell values and ratios in the DIC-exposed animals were 8-44% greater and in BIC-treated animals 0-11% greater than control animals of the same gestational age. Percentage of body water was the same in the experimental and control animals. The differences in DNA, RNA, and protein are believed to be related to drug-induced growth retardation incident to total fetal DNA reduction resulting in diminished cell number.     

超声多参数在预测妊娠期糖尿病巨大儿分娩方式中的临床价值

摘要 目的：探究超声多参数在预测妊娠期糖尿病巨大儿分娩方式中的应用价值。方法：选择2016年2月至2020年9月于中国人民解放军联勤保障部队第九○一医院（我院）分娩的156例妊娠期糖尿病产妇为研究对象,回顾性分析其一般临床指标及多普勒超声检测参数,按照新生儿是否为巨大儿区分为巨大儿组（52例）和非巨大儿组（104例）,对比两组胎儿超声参数差异,评估胎儿双顶径（biparietal diameter,BPD）、头围（head circumference,HC）、腹围（abdominal circumference,AC）及股骨长度（femur length,FL）与新生儿体重的相关性,纳入年龄、宫高、孕妇腹围、孕妇体重、BPD、HC、AC、FL等指标评估巨大儿单因素影响因素,最后多因素Logistic回归分析探究巨大儿独立危险因素。结果：（1）比较显示巨大儿组胎儿BPD、HC、AC和HL均大于非巨大儿组（P<0.05）;（2）Spearman相关性分析显示BPD、HC、AC和HL均与新生儿体重呈正相关（P<0.05）;（3）分析显示产妇宫高、产妇腹围、孕期增重、BPD、HC、AC和HL均为巨大儿单因素影响因素（P<0.05）;（4）Logistic多因素回归分析显示孕妇宫高、BPD、HC、AC为巨大儿独立危险因素。结论：孕期使用超声多参数对妊娠期糖尿病产妇巨大儿发生情况具有较好的预测价值,可协助医师了解胎儿相关指标,并据此选择合适的分娩方式,值得临床推广应用。     

Inhibiting matrix metalloproteinases with prinomastat produces abnormalities in fetal growth and development in rats

BACKGROUND: Matrix metalloproteinases (MMPs) play key roles in remodeling of the extracellular matrix during embryogenesis and fetal development. The objective of this study was to determine the effects of prinomastat, a potent selective MMP inhibitor, on fetal growth and development. METHODS: Prinomastat (25, 100, 250 mg/kg/day, p.o.) was administered to pregnant female Sprague-Dawley rats on gestational days (GD) 6-17. A Cesarian section was carried out on GD 20 and the fetuses were evaluated for viability and skeletal and soft tissue abnormalities. RESULTS: Prinomastat treatment at the 250 mg/kg/day dose produced a decrease in body weight and food consumption in the dams. A dose-dependent increase in post-implantation loss was observed in the 100 and 250 mg/kg/day-dose groups, resulting in only 22% of the dams having viable litters for evaluation at the 250 mg/kg/day dose. Fetal skeletal tissue variations and malformations were present in all prinomastat treated groups and their frequency increased with dose. Variations and malformation in fetal soft tissue were also increased at the 100 and 250 mg/kg/day doses. Prinomastat also interfered with fetal growth of rat embryo cultures in vitro. CONCLUSIONS: These data confirm that MMP inhibition has a profound effect on fetal growth and development in vivo and in vitro.     

Intra-amniotic endotoxin increases pulmonary surfactant proteins and induces SP-B processing in fetal sheep

Intra-amniotic (IA) endotoxin induces lung maturation within 6 days in fetal sheep of 125 days gestational age. To determine the early fetal lung response to IA endotoxin, the timing and characteristics of changes in surfactant components were evaluated. Fetal sheep were exposed to 20 mg of Escherichia coli 055:B5 endotoxin by IA injection from 1 to 15 days before preterm delivery at 125 days gestational age. Surfactant protein (SP) A, SP-B, and SP-C mRNAs were maximally induced at 2 days. SP-D mRNA was increased fourfold at 1 day and remained at peak levels for up to 7 days. Bronchoalveolar lavage fluid from control animals contained very little SP-B protein, 75% of which was a partially processed intermediate. The alveolar pool of SP-B was significantly increased between 4 and 7 days in conjunction with conversion to the fully processed active airway peptide. All SPs were significantly elevated in the bronchoalveolar lavage fluid by 7 days. IA endotoxin caused rapid and sustained increases in SP mRNAs that preceded the increase in alveolar saturated phosphatidylcholine processing of SP-B and improved lung compliance in prematurely delivered lambs.     

Gestational age-dependent effects of lipopolysaccharide on prostaglandin production by murine decidual caps

We sought to determine whether the gestational age of the pregnant mouse had any relationship with its lipopolysaccharide (LPS) responsiveness. Murine decidual caps from days 13, 15 and 17 of gestation (term is day 20) were dissected out, placed in inserts and equilibrated in media overnight. The following day, media were removed, replaced with fresh media (+/-LPS at 10 microg/mL). After LPS stimulation (24 h), prostaglandin (PG)E2 production by decidual caps from days 13 and 15 increased by 80-fold and 5-fold, respectively. PGF2alpha, 6-keto-PGF1a and TxB2 production also increased. Day 17 decidual caps were unaffected by LPS, pregnant mice inoculated i.p. with LPS (50 microg) at day 13 of gestation induced 100% delivery within 24 h. However, mice treated at days 15 and 17 had an equal occurrence of premature delivery or fetal resorption. This change in LPS responsiveness may indicate changes in the fetal-maternal immune system in late pregnancy.     

Maternal age and parity influence ultrasonographic measurements of fetal growth in Dutch Warmblood mares

Ultrasonographic examination of the equine fetus in mid-late gestation is usually performed only if there are concerns about fetal or maternal health. Even then it is difficult to determine whether development is ‘normal’ for gestational age because the reference values include considerable error margins. This study examined maternal factors that influence fetal growth with the aim of producing more precise late gestation fetal growth curves for Dutch Warmblood horses. Fetal development was monitored at 2-week intervals from day 100 of gestation until term in 32 mares ranging from 4 to 18 years in age; seven of the mares were primiparous. Transrectal and/or transabdominal ultrasonographic measurement of the fetal eye orbit, cranium, aorta, heart rate and of the combined thickness of uterus and placenta (CTUP) were performed using a portable ultrasound machine equipped with 6 MHz linear and 3.5 MHz curved array probes.During days 100–250 of gestation, the CTUP was thicker in primiparous than multiparous mares (p < 0.05). After day 220 the maximum cross-sectional area, but not diameter, of both the eye orbit and cranium were also greater in primiparous than multiparous mares (p < 0.05). Fetal aorta diameter was not influenced by parity but was affected by maternal age, being smaller in mares ≥15 years of age than younger animals (p < 0.05). Only biparietal cross-sectional surface area and aorta diameter increased linearly throughout late gestation. However, even allowing for the effects of parity and maternal age, the late gestational variation in fetal size is such that serial measurements may be required to definitively identify abnormal development.     

Accuracy of canine parturition date prediction using fetal measurements obtained by ultrasonography

The length of canine gestation is 65 days from the luteinizing hormone (LH) surge. Early and accurate determination of canine gestational age is useful for predicting and managing parturition. We performed a retrospective study on fetal measurements obtained by transabdominal ultrasonographic examination of 83 bitches (32 breeds) to estimate gestational age. Gestational age was estimated using two published tables correlating either (1). embryonic vesicle diameter (EVD), crown-rump length (CRL), body diameter (BD), and biparietal diameter (HD) to the LH surge in mid-gestational beagles or (2). BD and HD to parturition in late-gestation retrievers. Parturition date was predicted by obtaining the difference between the gestational age estimate and 65 days. Bitches were divided into four body weight (BW) groups based on nonpregnant body weight: small (9-20 kg), large (>20-40 kg), and giant (>40 kg). Mean+/-S.D. litter size (LS) was calculated for each BW group. The BW groups were then divided into small, average, or large LS groups. The accuracy of the prediction was not affected by LS but was affected by maternal body weight for small and giant BW groups only. When adjusted for weight, the accuracy of prediction within +/-1 day and +/-2 day intervals was 75 and 87%, respectively. Using stepwise logisitic regression, the most accurate prediction of parturition date was obtained when fetuses were measured at 30 days after the LH surge, regardless of body weight or LS. Parturition date predictions made after 39 days of gestation using only biparietal and BD fetal measurements were <50% accurate within +/-2 days.     

The effects of maternal undernutrition on maternal and fetal serum insulin-like growth factors, thyroid hormones and cortisol in the guinea pig.

The insulin-like growth factors (IGF-I and -II) are potential mediators of the effects of maternal undernutrition on fetal growth and muscle development. The effects of a 40% reduction in maternal feed intake on serum levels of the IGFs, the thyroid hormones and cortisol, were investigated for the last two trimesters (day 25 to birth). This level of undernutrition is known to cause a 35% reduction in fetal and placental weights, and a 20-25% reduction in muscle fibre number. Maternal IGF-I level was greater than non-pregnant levels on day 25 gestation, in both control and restricted dams, and declined with gestational age. The increase in IGF-I level in the 40% restricted group was approximately two-thirds that of control animals. Fetal serum IGF-I was also reduced in undernourished fetuses throughout gestation. Maternal IGF-II did not change with gestational age and was unaffected by undernutrition. Fetal IGF-II reached a peak at day 55 of gestation, this peak was greatly diminished by maternal feed restriction. Both IGF-I and IGF-II tended to be related to fetal, placental and muscle weights at day 65 of gestation. Thyroid hormone concentration declined in maternal serum and increased in fetal serum with increasing gestational age. Levels were not significantly affected by undernutrition. Both triiodothyronine (T3) and thyroxine (T4) were correlated with IGF-I in maternal serum (P < 0.05), but not in fetal serum. Cortisol levels were elevated by undernutrition in both maternal and fetal serum, and increased with gestational age. Cortisol was inversely correlated with serum IGF-I in both maternal and fetal serum. Maternal serum IGF-I may mediate the effects of undernutrition on fetal growth by affecting the growth and establishment of the feto-placental unit in mid-gestation. Fetal IGF-I may mediate the effects on muscle growth, whereas IGF-II seems to be related to hepatic glycogen deposition. Cortisol may play a role via its effect on the IGFs, but the thyroid hormones are unlikely to be important until the late gestation/early postnatal period.     

Early pregnancy diagnosis by the ultrasonographical device and observation of fatal growth in cynomolgus monkeys (Macaca fascicularis)

Usefulness of the ultrasonographical device (USD) for early diagnosis of pregnancy and for observation of fetal growth was examined in the cynomolgus monkey (Macaca fascicularis). Firstly, 50 females, each of which was mated for 24 hours in an individual cage, were used. They were diagnosed for pregnancy by the use of USD 15 to 29 days and 35 days after mating. Then, 20 of them were judged to be pregnant. The early pregnancy diagnosis was based on the detection of gestational sac (GS) in the uterus. The GS was detected 20.0 +/- 1.8 days after mating. The duration from the day on which GS was first detected to the day on which the heart beat of embryo (HBE) was detected averaged 5.6 +/- 1.5 days. In 17 of these 20 pregnancies, GS was detected 17 to 23 days after mating. As regards the remaining three pregnant cases, GS and HBE were simultaneously detected on the 28th day of pregnancy in two cases, and on the 35th day in one case. Secondly, 225 females who were mated by the routine 3 day-mating system were used. Pregnancy diagnosis by USD was conducted on the 21st, 28th and 35th day after mating. Ninety-six of the 225 females were judged to be pregnant. In 33 (34.1%) of the 96 pregnant cases, GS was detected on the 21st day of pregnancy. In 57 females (59.4%), GS was detected on the 35th day. Furthermore, it was able to judge conditions of fetal growth by measuring the size of GS and biparietal diameter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nutritional control of respiratory and other muscular activities in relation to plasma prostaglandin E in the fetal sheep

The effects of nutrient availability on fetal plasma prostaglandin E (PGE) concentrations, on fetal breathing movements and electromyographic (EMG) activities of fetal nuchal and forelimb muscles were investigated in pregnant ewes by varying dietary intake and by manipulation of fetal plasma glucose concentration. The incidence of fetal breathing movements (06.00-10.00 h) decreased with increasing gestational age while fetal arterial concentrations of plasma PGE increased significantly over the same period of gestation. Maternal fasting for 48 h reduced the incidence of fetal breathing movements and the amount of nuchal EMG activity (06.00-10.00 h) in animals older than 130 days but had no effect earlier in gestation. No changes in forelimb EMG activity were observed during fasting at any gestational age. Plasma PGE levels increased significantly during fasts begun both before and after 130 days of gestation. When data from fed and fasted states were combined for all fetuses, irrespective of gestational age, there was a significant inverse correlation between fetal breathing movements incidence and plasma PGE concentration in utero. This relationship was even more pronounced when the fetuses were considered individually. Insulin infusions induced hypoglycaemia, an increase in fetal plasma PGE concentration and a significant reduction in the incidence of fetal breathing movements at all ages. Glucose infusions of fetal breathing movements only after 130 days and had no effect on plasma PGE levels in utero at any gestational age. Neither insulin nor glucose infusions altered the EMG activities of the nuchal and forelimb muscles. The results show that glucose availability is an important factor in determining the incidence of fetal breathing movements in utero and indicate that nutritionally induced changes in fetal breathing movements are mediated in part by PGE. They also suggest that PGE is a physiological regulator of fetal breathing movements in the sheep during late gestation.