Serum cortisol levels affect the metabolic clearance rate of progesterone in female baboons.

Since interactions between progesterone (P₄), Cortisol (F), cortisone (E) and corticosteroid binding globulin (CBG) may influence the metabolic clearance rates (MCR) of these steroids, the effect of altering circulating F concentrations on clearance of the steroids was determined. MCR of P₄, F and E were determined by the iv constant infusion method in 6 pregnant and 6 nonpregnant baboons (Papio papio). Serum F concentrations were altered by iv infusion of 5 mg F/90 min or im injection of betamethasone (3 mg bi-daily for 2 days). Mean MCR-P₄ (1/d/kg ± SE) was greater (P < 0.01) in pregnant (92.8 ± 8.5) than in nonpregnant (53.9 ± 4.4) animals while mean MCR-F was similar in both groups ($\text{10.8 ± 1.2}\text{vs}\text{13.0 ± 1.5}$, respectively). Mean MCR-E was also similar in pregnant (30.8 ± 4.9) and nonpregnant (34.1 ± 4.5) baboons. Mean serum F concentrations (/gmg/100 ml ± SE) in 4 nonpregnant (42.0 ± 8.6) and 4 pregnant (52.2 ± 10.0) baboons were increased (P < 0.05) 60% by F administration but MCR-P₄, -F and -E were unaltered. Betamethasone treatment reduced (P < 0.05) serum F 75% in both groups. In nonpregnant baboons, betamethasone treatment reduced (P < 0.01) MCR-P₄ (37.3 ± 3.9), MCR-F (7.4 ± 1.6) and MCR-E (18.5 ± 3.7). Betamethasone treatment of pregnant animals reduced (P < 0.01) MCR-P₄ (56.5 ± 7.4), MCR-F (6.3 ± 0.8) and MCR-E (14.6 ± 2.6). Infusion of F into betamethasone-treated animals increased serum F levels and increased MCR-P4, -F and -E. It is concluded that variations in serum F levels affect the clearance of F, E and P₄ presumably because of the mutual interactions of these steroids with CBG.     

Serum leptin in nonpregnant and pregnant women and in old and new world nonhuman primates

Leptin is a hormone that is produced during mammalian pregnancy in the placental trophoblast and other tissues, including! fetal and maternal adipocytes. Synthesis of the polypeptide and the presence of its specific receptors throughout the human maternal fetoplacental unit suggest direct effects on conceptus growth and development. However, both the physiologic roles of leptin and the mechanisms regulating leptin synthesis in human pregnancy differ from those in laboratory and domestic species, necessitating the development of non-human primate research models. Therefore, we compared serum leptin concentrations in nonpregnant and pregnant women with those in both old world nonhuman primates (i.e., baboon, rhesus monkey, cynomolgus monkey) and new world nonhuman primates (i.e., squirrel monkey, titi monkey). As expected, maternal leptin levels were elevated in human and baboon pregnancies (P < 0.05 and P < 0.001, respectively). Levels in both species of old world monkeys were also greatly enhanced (P < 0.001). Although maternal serum concentrations were slightly elevated compared to nonpregnant levels in both species of new world monkeys, overall concentrations were dramatically lower than for either old world primates or humans. Results provide comparisons of serum leptin concentrations in pregnant and nonpregnant humans and baboons with those in both old and new world monkeys and further characterize these nonhuman primates as models for the investigation of leptin dynamics in pregnancy.     

Effect of estrogen on the metabolism of cortisol and cortisone in the baboon fetus at midgestation

To determine whether the metabolism of cortisol (F) and cortisone (E) in the baboon fetus is regulated by estrogen, fetal interconversion of F/E was measured at midgestation after an experimental increase in placental estradiol (E2) production. Six baboons (Papio anubis) received increasing numbers of androstenedione implants (50 mg) inserted s.c. at 8-day intervals between Days 70 and 100 of gestation (term = Day 184) to elevate the production of estrogen; controls (N = 8) received no treatment. On Day 100 of gestation, each animal was anesthetized with ketamine:halothane/nitrous oxide, the fetus was exteriorized and [3H] F/[14C] E was infused via a fetal femoral vein for 70 min. Blood samples were then obtained from the contralateral fetal femoral vein, the umbilical vein/artery, and a maternal saphenous vein. After purification of F and E, the metabolic clearance rate (MCR), peripheral interconversion, and placental extraction of F and E were calculated. Maternal serum E2 concentrations (ng/ml; mean +/- SE) between Days 80 and 100 of gestation were greater (p less than 0.01) in androstenedione-treated baboons (2.2 +/- 0.2) than in untreated controls (1.2 +/- 0.1). Although the MCR of F was similar in control (5.2 +/- 0.3 1/day) and treated (7.7 +/- 1.0 1/day) animals, the MCR of E (13.5 +/- 2.0 1/day) was increased (25.8 +/- 2.5 1/day; p less than 0.05) by androstenedione treatment. Placental extraction of F (59 +/- 9%) was lower (p less than 0.01) than that of E (82 +/- 5%) in untreated baboons and was not affected by androstenedione treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy termination by prostaglandin F2α stimulates maternal behavior in the rat

Treatment with PGF_2α resulted in the termination of pregnancy in 16- and 19-day pregnant rats, but not in 10- or 13-day pregnant rats. Rats that aborted displayed a rapid onset of maternal behavior when tested with foster pups. Aborted rats also displayed sexual receptivity and ovulation: these phenomena resemble the sequence of events following hysterectomy on the same days of pregnancy. Both can be related to the events surrounding normal parturition in the rat. The results are interpreted as due to a pregnancy-induced deactivation of the factor in the uterus that prevents estrogen from stimulating maternal behavior in nonpregnant females. In the absence of this factor, the PGF_2α-induced rise in estrogen secretion facilitates maternal behavior and sexual behavior and induces ovulation.     

Normal concentrations of essential and toxic elements in pregnant baboons and fetuses (Papio species)

Heavy metals are essential for the normal progression of maternal and fetal tissue growth and metabolism in pregnancy. Considerable data have been collected for concentrations of various elements in pregnant women, but no comprehensive evaluation of element concentrations in any non-human primate model has been performed. Baboons were studied at the second half of pregnancy. Forty essential and toxic element concentrations were analyzed by absorption spectrophotometry in paired maternal and fetal blood samples; hair and nail samples in pregnant baboons; in placenta, amniotic fluid; and fetal femur, lymph nodes, and liver. Concentrations demonstrated an excellent correlation with concentrations reported in late human pregnancy. Twenty-four elements were below detectable limits in various specimens. We conclude that the pregnant baboon offers unique opportunities to study both normal maternal, fetal, and placental physiology as well as the environmental toxicology of these elements. This information and the ability to use the pregnant baboon as a model is important because essential and toxic elements are key components of the diet as well as major products of manufacturing processes within our industrialized society.     

Regulation of placental villous angiopoietin-1 and -2 expression by estrogen during baboon pregnancy

We recently showed an increase in vascular endothelial growth factor (VEGF), decrease in angiopoietin-1 (Ang-1) and unaltered Ang-2 expression by the villous placenta with advancing baboon pregnancy. Moreover, placental VEGF expression was increased by estrogen in early pregnancy. In the present study, we determined whether placental Ang-1 and Ang-2 are regulated by estrogen. Ang-1 and Ang-2 mRNA and protein were determined by RT-PCR and immunocytochemistry in the placenta of baboons on Day 60 of gestation (term is 184 days) after administration of estrogen precursor androstenedione on Days 25-59 or on Day 54 after acute estradiol administration. Chronic androstenedione treatment increased serum estradiol levels three-fold (P < 0.001) and decreased (P < 0.05) villous cytotrophoblast Ang-1 mRNA to a level (0.36 +/- 0.08 relative to 18S rRNA) that was one-third of that in untreated animals (0.98 +/- 0.26). Within 2 hr of estradiol administration, cytotrophoblast Ang-1 mRNA was decreased to a level (0.24 +/- 0.05) one-fifth (P < 0.05) of that in untreated animals (1.14 +/- 0.23). However, Ang-2 mRNA levels were unaltered. Ang-1, Ang-2 and estrogen receptors alpha and beta protein were localized within villous cytotrophoblasts providing a mechanism for estrogen action at this site. In summary, estrogen increased VEGF, decreased Ang-1, and had no effect on Ang-2 expression within placental cytotrophoblasts during early baboon pregnancy. We propose that the estrogen-dependent differential regulation of these angioregulatory factors underpins the unique pattern of neovascularization established within the villous placenta during primate pregnancy.     

Ontogeny of hematological cell and biochemical profiles in maternal and fetal baboons (Papio species)

The normal ranges of hematological cell profiles and biochemistry are documented in adult non-pregnant, pregnant, juvenile, and neonatal baboons. Despite the extensive use of the baboon as a model for the study of various aspects of pregnancy, there is no data from paired mothers and their fetuses at different stages of gestation. Hematologic and biochemical profile data were obtained from eight non-pregnant female baboons, 37 mothers and 38 fetal baboons at 30 +/- 2, 90 +/- 2, 125 +/- 2, and 175 +/- 2 days of gestation (mean +/- range; dGA; term, 180 dGA). Changes observed in fetal and maternal blood during normal baboon pregnancy were similar to those reported in human pregnancy. The level of alkaline phosphatase was two times higher in fetal blood circulation than that reported in human pregnancy.     

Pregnancy-stimulated growth of vascular smooth muscle cells: Importance of protein kinase C-dependent synergy between estrogen and platelet-derived growth factor

Dramatic smooth muscle cell (SMC) growth occurs in the uterine artery during pregnancy. The potential for pregnancy-associated growth may also exist at other vascular sites. We tested the hypothesis that increased growth of uterine artery SMC isolated from pregnant (vs. nonpregnant) guinea pigs would be detectable in culture, that pregnancy-associated phenotypic changes would also be found in nonuterine vascular cells (aortic SMC), and that the enhanced growth would be dependent on estrogen, peptide growth factors like platelet-derived growth factor (PDGF), and protein kinase C (PKC). Growth responses were measured by [³H]-thymidine incorporation and cell counts. Uterine artery SMC from pregnant guinea pigs grew to a higher plateau density with serum stimulation, had increased spontaneous DNA synthesis and persistent growth following serum withdrawal, and were more responsive to 3–30 ng/ml PDGF-BB than nonpregnant cells. Aortic SMC from pregnant animals also grew to a higher plateau density and had enhanced responsiveness to PDGF-BB. This increased response to PDGF-BB by pregnant uterine artery and aortic SMC (40–233% increase over nonpregnant PDGF result) was reproduced in nonpregnant cells by pretreatment for 1–24 h with 17-beta(β)-estradiol (30–100 nM). Neither the pregnancy-induced difference nor the estradiol pretreatment was associated with increased PDGF-BB binding activity. The synergistic effect of 17β-estradiol was partially (62%) reproduced with 17-alpha(α)-estradiol, an isomer which does not bind the estrogen receptor. This suggested that 17β-estradiol modulates the PDGF-BB response by both estrogen-receptor- and nonreceptor-mediated mechanisms. To test if the estrogen effects were dependent on PKC, two different antagonist strategies (3 μM dihydrosphingosine and phorbol-ester-induced downregulation) were applied prior to 17α- or β-estradiol and blocked the enhanced responses to PDGF. The synergistic effect of 17β-estradiol on PDGF was then reproduced by 1 h pretreatment with the cell-permeable PKC activator, 10 nM PMA. We conclude that pregnancy stimulates increased growth of uterine and aortic SMC in vitro which is dependent on estrogen, PDGF, and PKC and may be important in vascular remodeling during pregnancy. © 1996 Wiley-Liss, Inc.     

Serum and fecal steroid analysis of ovulation,pregnancy, and parturition in the black rhinoceros (Diceros bicornis)

Studies were conducted to determine: (1) if fecal hormone metabolite concentrations correlated with serum estrogen and progesterone concentrations, follicular activity and reproductive behavior in the black rhinoceros (Diceros bicornis) and (2) if threshold values of respective fecal metabolite concentrations correlated with pregnancy. Blood and fecal samples were collected, in conjunction with transrectal ultrasound and behavior observations, for an 18-month period from one black rhinoceros female. Subsequently, serial fecal samples were collected from 13 females in 10 zoos. Quantitative analysis of serum progesterone (P₄) and estradiol (E₂) was performed by radioimmunoassay (RIA): analysis of fecal estrogen metabolites (E) and fecal progesterone metabolites (P) were performed by enzyme immunoassay (EIA). Serum P₂ concentrations identified two luteal phase patterns and two nadirs which corresponded with behavioral estrus. Fecal E patterns indicated a sharp peak which corresponded with breeding. concentrations of fecal P illustrated identifiable nadirs and several peaks which corresponded to serum P₄ nadirs and luteal phases. Serum P₄ concentrations were not different between the luteal phase and pregnancy. Fecal P concentrations started to rise above luteal phase concentrations approximately 150 days postbreeding and remained elevated until immediately before parturition. Serum E₂ and fecal E concentrations rose and subsequently declined after parturition. In the fecal samples from seven pregnant females, fecal P concentrations were similarly elevated compared to six nonpregnant females. Results indicated that fecal steroid metabolites accurately reflected serum steroid hormone concentrations and that the measurement of P and E concentrations permitted the characterization of the estrous cycle, the diagnosis of pregnancy, and the onset of parturition. Zoo Biol 16:121–132, 1997. © 1997 Wiley-Liss, Inc.     

Endogenous estrogen mediates vascular reactivity and distensibility in pregnant rat mesenteric arteries

The role of estrogen in the maternal systemic cardiovascular adaptations during pregnancy is still controversial. Female Sprague-Dawley rats were implanted at day 14 of pregnancy with either a 50-mg tamoxifen pellet (estrogen receptor blocker, n = 10) or placebo pellet (n = 10). Virgin female rats were a nonpregnant control (n = 7). At days 20-22 of pregnancy, resistance-sized mesenteric arteries were mounted onto a dual-chamber arteriograph system. Pregnancy significantly blunted the pressor response to phenylephrine [measurement of the effective concentration that yielded 50% maximum response (EC(50)) values were 1.5 +/- 0.22 vs. 0.69 +/- 0.16 microM (P < 0.05)] and enhanced vasodilation to ACh [EC(50) = 1.13 +/- 2.53 vs. 3.13 +/- 6.04 nM (P < 0.05)] compared with nonpregnant rats. However, tamoxifen treatment during pregnancy reversed these effects. Inhibition of nitric oxide (NO) synthase with N(G)-monomethyl-L-arginine (250 microM) shifted only the responses of the placebo-treated pregnant group to both phenylephrine and ACh. Arterial distensibility in the placebo-treated pregnant group was also significantly increased (P < 0.05) compared with nonpregnant and tamoxifen-treated pregnant animals. In summary, endogenous estrogen during pregnancy increases NO-dependent modulation of vessel tone and arterial distensibility.     

X-linked,polymorphic genetic variation of thyroxin-binding globulin (TBG) in baboons and screening of additional primates

X-linked polymorphic variation of thyroxin-binding globulin (TBG) is observed in several human groups. Isoelectric focusing of plasma samples labeled in vitro with [¹²⁵I]thyroxin, followed by autoradiography, also reveals genetically determined polymorphic electrophoretic variation in baboon TBG. The protein detected by this method in baboon plasma is immunologically similar to human TBG and is distinct from the other thyroxin-binding proteins, albumin and prealbumin. The isoelectric patterns of human and baboon TBG are very similar and both have an isoelectric range of pH 4.1 to 4.5. The baboon TBG polymorphism is inherited in a two-allele X-linked fashion, with a frequency of 72% for the common allele and 28% for the slow allele. A survey of seven other primate species including African green monkey, bonnet macaque, chimpanzee, crab-eating macaque, gorilla, rhesus monkey, and spider monkey revealed no polymorphic variation in TBG, although isoelectric patterns were similar to the human and baboon patterns. In addition, samples from pregnant chimpanzees demonstrate a pronounced quantitative anodal shift in relative band densities, a shift also observed in pregnant humans. This shift was not observed in samples from pregnant baboons. TBG should prove to be a useful X-linked genetic marker in baboons and provides a model of serum protein changes in pregnancy, at least in humans and chimpanzees.This research was supported by NIH Grant 2R01-EY-02388 and a Biomedical Research Support Grant from the Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston.     

Opposing effects of androgen and estrogen on pituitary-adrenal function in nonpregnant primates

Maternal administration of androstenedione produces a sustained fall in maternal plasma adrenocorticotropic hormone (ACTH) concentrations in the pregnant nonhuman primate. We hypothesize a negative feedback influence on the maternal hypothalamo-pituitary-adrenal (HPA) axis by androgens in primates. This may reflect an important maternal adaptation during pregnancy in primates preventing premature induction of labor by maternal stress. However, androstenedione is precursor for placental estradiol-17beta synthesis, and infusion of androstenedione into pregnant primates elevates maternal plasma estradiol-17beta to term concentrations. Thus, it could be argued that 1) the effects attributed to androstenedione on the maternal HPA axis are mediated by estrogen rather than by androgen and 2) the negative influence of androgens may be on placental ACTH rather than, or in addition to, pituitary ACTH. To discriminate between androgenic and estrogenic effects of androstenedione on pituitary and/or placental ACTH function in primates we measured plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations in nonpregnant baboons after treatment with either androstenedione or estradiol-17beta. Nine female baboons were studied between 14 and 22 days postpartum prior to estrous cycling. After 2 days of baseline, a continuous i.v. infusion of androstenedione (1.5 mg/kg per h in 10% intralipid, IL) was started at 0900 h and maintained for 9 days in 3 baboons. A similar protocol was carried out in another 3 baboons that received a continuous i.v. infusion of estradiol-17beta (10 microg/kg per h in 10% IL) instead of androstenedione. Three additional baboons received continuous i.v. IL vehicle alone and served as controls. Arterial blood samples (0.5 ml) for measurement of plasma hormones were taken during baseline and after 1, 3, 5, 7, and 9 days of infusion. Baseline plasma ACTH, DHEAS, and cortisol concentrations were similar among all groups. Plasma ACTH did not change during IL, increased following estradiol-17beta, and fell during androstenedione treatment. Accordingly, plasma cortisol and DHEAS concentrations were also unaltered by IL, and both steroids increased during estradiol-17beta treatment. In contrast, plasma cortisol and DHEAS remained unaltered from baseline during androstenedione treatment, despite the fall in plasma ACTH measured at this time. These data in the nonpregnant baboon 1) are consistent with negative feedback on pituitary ACTH by androgens and 2) demonstrate a positive influence on pituitary-adrenal function by estrogen in primates.     

Effect of uncomplicated pregnancy on body water content and distribution in baboons

Body water content and distribution were estimated before, during, or after 32 pregnancies in baboons. Water content of the various compartments (in liters) correlated with body weight in both nonpregnant and pregnant baboons, and with length of gestation in pregnant baboons. In proportion to body weight (in ml/kg), most water compartments did not change significantly with length of gestation. Mean plasma volume and blood volume were higher during pregnancy than before or after.     

A study of prostaglandin F2α as the luteolysin in swine: V comparison of prostaglandin F, progestins, estrone and estradiol in uterine flushings from pregnant and nonpregnant gilts

Uterine flushings were collected from 38 gilts representing Days 6,8,10,12,14,15,16 and 18 of the estrous cycle and pregnancy. The same group of gilts were represented within each of the respective days of the estrous cycle and pregnancy, i.e., three to six gilts per day per status. Uterine flushings (about 40ml) were assayed for prostaglandin F (PGF), estrone (E₁), estradiol (E₂), progestins (P) and protein. Nonpregnant gilts had higher (P<.01) concentrations of P in uterine flushings than pregnant gilts, but pregnant gilts had higher (P<.01) E₁ and E₂ concentrations. Significant day by status interactions were detected for E₁ (P<.05), but not for E₂ concentrations in uterine flushings. Total recoverable PGF and PGF concentrations in uterine flushings were greater (P<.01) in pregnant than nonpregnant gilts and significant (P<.01) day by status interactions were detected. In nonpregnant gilts, PGF increased between Days 12 and 16, i.e., during the period of corpora lutea (CL) regression. In pregnant gilts, PGF in uterine flushings increased markedly between Days 10 and 18. Total recoverable PGF on Day 18 of the estrous cycle was only 464.5 ± 37.6 ng as compared to 22,688.1 ± 1772.4 ng on Day 18 of pregnancy. Total recoverable protein was also higher (P<.01) in pregnant gilts. These data indicate that PGF synthesis and secretion by the uterine endometrium and/or conceptuses is not inhibited during pregnancy and suggest that PGF is sequestered within the uterine lumen of pregnant gilts, as is the total protein component of endometrial secretions referred to as histotroph.     

Binding and retention of estrogen in the uterus of hamsters treated neonatally with diethylstilbestrol

We have shown previously that postpubertal estrogen exposure promotes the development of uterine tumors in hamsters treated neonatally with diethylstilbestrol (DES). The purpose of this study was to determine if the uterine estrogen receptor system of adult hamsters was altered after neonatal DES treatment. There was no effect on the concentration, subcellular distribution, apparent binding affinity, sedimentation properties, surface charge characteristics or ligand specificity of uterine estrogen receptor in ovariectomized, estrogen-replaced animals. Furthermore, neonatal DES treatment had no effect on the subcellular distribution of radioactivity in the uterus of adult animals ovariectomized 1 week before challenge with [³H]-estradiol-17β(E₂). However, the amount of radioactivity taken up and specifically bound within the uterus 6 h after [³H]-E₂ challenge was less in DES-treated compared to control animals. Six hours after challenge with unlabeled E₂, the concentration (pmol/g tissue) of occupied but not total nuclear estrogen receptor was reduced in DES-treated animals. The difference in uterine radioactivity levels and occupied nuclear receptor retention appears to be due to a difference in estrogen metabolism since the systemic concentration of authentic [³H]-E₂ was lower in DES-treated animals compared to control. These results demonstrate no DES-induced change in the physicochemical or functional properties of the uterine estrogen receptor system, suggesting that a lesion in this receptor system is not involved in the etiology of uterine tumor development following neonatal DES exposure. However, the DES-treated animal appears to have an enhanced estrogen metabolism.     

Developmental regulation of baboon fetal ovarian maturation by estrogen

Ovarian function in adult human and nonhuman primates is dependent on events that take place during fetal development, including the envelopment of oocytes by granulosa (i.e., folliculogenesis). However, our understanding of fetal ovarian folliculogenesis is incomplete. During baboon pregnancy, placental production and secretion of estradiol into the fetus increases with advancing gestation, and the fetal ovary expresses estrogen receptors alpha and beta in mesenchymal-epithelial cells (i.e., pregranulosa) as early as midgestation. Therefore, the current study determined whether estrogen regulates fetal ovarian follicular development. Pregnant baboons were untreated or treated with the aromatase inhibitor CGS 20267, or with CGS 20267 plus estradiol benzoate administered s.c. to the mother on Days 100-164 (term = Day 184). On Day 165, baboon fetuses were delivered by cesarean section and the number of total follicles and interfollicular nests consisting of oocytes and mesenchymal-epithelial cells in areas (0.33 mm(2)) of the outer and inner cortices of each fetal ovary were quantified using image analysis. Maternal and umbilical serum estradiol levels were decreased by >95% with CGS 20267. Treatment with CGS 20267 and estrogen restored maternal estradiol to normal and fetal estradiol to 30% of normal. Although fetal ovarian weight was unaltered, the mean number of follicles +/- SEM/0.33 mm(2) in the inner (59.0 +/- 1.7) and outer (95.3 +/- 2.4) cortical regions of fetal ovaries in untreated animals was 35%-50% lower (P < 0.01) in estrogen-depleted baboons (25.9 +/- 1.4, inner cortex; 62.5 +/- 2.7, outer cortex) and was restored to normal by treatment with CGS 20267 and estrogen. In contrast, the number of interfollicular nests was 2-fold greater (P < 0.01) in fetal ovaries of estrogen-suppressed animals, a change that was prevented by treatment with estrogen. In summary, fetal ovarian follicular development was significantly altered in baboons in which estrogen was depleted during the second half of gestation and restored to normal by estradiol. We propose that estrogen plays an integral role in regulating, and perhaps programming, primate fetal ovarian development.     

Erythrocyte metallothionein in relation to other biochemical zinc indices in pregnant and nonpregnant women

Erythrocyte metallothionein (E-MT) is considered a promising index of zinc status in humans, since it may be more sensitive than other biochemical indices to changes in dietary zinc. However, conditions of high zinc demand with substantial redistribution of tissue zinc and specific changes in hormone profile, such as pregnancy, may have an influence on E-MT levels in addition to dietary zinc. In this study, we compared E-MT concentrations in relation to other biochemical zinc indices in healthy pregnant women at delivery (n=40) and nonpregnant women (n=22) with similar habitual dietary zinc intakes (average 13.3 mg/d). Pregnant women had lower serum zinc and albumin-bound serum zinc, but higher levels of {ie115-1}-macroglobulin-bound serum zinc than the nonpregnant women. Erythrocyte zinc (E-Zn) was similar in both groups, but E-MT (mean±SE) was slightly but significantly (p<0.05) higher in the pregnant women (2.9±0.09 nmol/g protein) compared to nonpregnant women (2.6±0.06 nmol/g protein). A significant correlation was observed between E-MT and E-Zn in the nonpregnant women (r=0.70;p<0.001), consistent with the role of intracellular zinc in the regulation of metallothionein synthesis. However, such correlation was not observed in the pregnant women, suggesting that E-MT levels in pregnancy may be influenced by factors related to the pregnant state.     

Haemodynamics using transthoracic echocardiography in healthy pregnant and non-pregnant baboons (Papio hamadryas)

Background To determine systolic and diastolic function using transthoracic echocardiography in the baboon (Papio hamadryas). Methods Transthoracic echocardiography was performed in eight non‐pregnant female and six pregnant baboons according to American Society of Echocardiography recommendations. Results Haemodynamic measurements were obtained from fourteen baboons. Compared to non‐pregnant baboons, pregnant baboons demonstrated: (mean ± SD, pregnant vs. healthy) increased cardiac output (1615 ± 121 ml/minutes vs. 1317 ± 134 ml/minutes P = 0.001) due to an increased heart rate [120 ± 11 beats per minute (BPM) vs. 105 ± 6 BPM P = 0.018]. The inter‐observer and intra‐observer variability (mean difference ± SD) for the left ventricular outflow tract diameter was 0.05 ± 0.07 cm and 0.01 ± 0.03 cm respectively. There was minimal impact to the animal’s daily activities. Conclusions Transthoracic echocardiography was applicable and reproducible for the assessment of haemodynamics in baboons thus enabling translation of animal results to human studies.