Pregnancy outcome in ethanol-treated mice with folic acid supplementation in saccharose

Introduction Maternal folic acid deficiency is the most important metabolic factor in the etiology of neural tube defects (NTD) and is reduced by ethanol, which is extensively consumed by young women. Objective The objective of the study was to determine whether folic acid supplementation in dietary saccharose is efficient in the prevention NTD induced by ethanol in fetuses of Swiss mice. Materials and methods Pregnant mice were divided into four groups of six animals each: control (C), ethanol (E), deficient-supplemented (DS), and deficient-supplemented+ethanol (DSE). Groups C and E received commercial mouse chow (containing 3 mg/kg folic acid) throughout the experiment, while groups DS and DSE received a folic acid-free diet with the addition of saccharose supplemented with folic acid (2 mg/kg folic acid) in water. Group E and DSE animals received ethanol (4 g/kg) administered intraperitoneally from the seventh to the ninth gestational day (gd) and were euthanized on the 18th gd, while groups C and DS received saline. Results Congenital anomalies were observed in groups E and DSE. The fetal weight and length of the animals in group E were lower than in groups C and DS and, in group DSE, were lower than in groups C and DS. The placental diameter of group E was smaller than that of group C, and the placental weight of group C animals was lower than that of groups E, DSE, and DS. Conclusion The study demonstrated that dietary supplementation with folate in saccharose is an accessible means of consumption that could be further diffused but in an increased dose than recommended to reduce the teratogenic effects of ethanol.

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia

Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms. We examined how three eNOS polymorphisms [T-786C, rs2070744; Glu298Asp, rs1799983; 27 bp variable number of tandem repeats (VNTR) in intron 4] affect plasma nitrite concentrations in 205 pregnant women [107 healthy pregnant (HP) and 98 PE]. Genotypes were determined and eNOS haplotypes were inferred using the PHASE 2.1 program. The plasma nitrite concentrations were determined using an ozone-based chemiluminescence assay. The Glu298Asp polymorphism had no effects on the plasma nitrite concentrations. Higher nitrite levels were found in HP women with the CC versus TT genotype for the T-786C polymorphism (277.9 +/- 19.5 versus 140.6 +/- 8.2 nM; P < 0.05). Lower nitrite levels were found in healthy women with the 4a4a versus 4b4b genotype for the VNTR polymorphism (95.1 +/- 3.3 versus 216.1 +/- 16.8 nM; P < 0.05). No effects of genotypes were found in PE women (all P > 0.05). The `C Glu b` haplotype was more frequent in the HP group than in the PE group (20 versus 5; P = 0.0044). This haplotype was associated with higher nitrite concentrations than the other haplotypes in healthy pregnancies (P < 0.05). No differences in nitrite concentrations were found among PE women with different eNOS haplotypes (P > 0.05). These findings indicate that eNOS polymorphisms affect endogenous NO formation in normal pregnancy, but not in PE, and that the `C Glu b` haplotype may protect against the development of PE by increasing endogenous NO formation.

Visceral leishmaniasis and pregnancy: analysis of cases reported in a central-western region of Brazil

Objectives Because of the large number of cases of visceral leishmaniasis (VL) recorded in Brazil over the last few years, this disease has been showing characteristics different from previously known ones. We report cases of pregnant women treated for VL, describing their course and outcome and the chemotherapeutic medication used according to the clinical signs and symptoms of each patient. Study design We report five cases of pregnant women treated for VL in a central-western region of Brazil. Results No case of vertical transmission was observed, even in patients who were treated after delivery. One of the patients with a late diagnosis made after the onset of symptoms died. Thus, the treatment of VL during pregnancy reduces maternal mortality and the rate of vertical transmission of the disease, being safe and effective as long as the disease is diagnosed early. Conclusion At present, amphotericin B and its derivatives appear to be the best therapeutic option for the mother-child binomial.

Influence of pregnancy and smoking on brachial artery flow-mediated dilation values and time until maximum response

To evaluate the effect of pregnancy and smoking on endothelial function using brachial artery flow-mediated dilation (FMD) and to determine the time necessary until the occurrence of maximum brachial artery dilation after stimulus. This study was an observational study evaluating 133 women, who were grouped as follows: non-smoking pregnant women (N = 47), smoking pregnant women (N = 33), non-smoking women (N = 34), and smoking pregnant women (N = 19). The diameter of the brachial artery was measured at baseline and at 30, 60, 90 and 120 s after stimulus. The relative change of brachial artery was determined for each of these four moments. FMD measured at 60 s after stimulus was compared between the groups. The maximum FMD was observed at 60 s after cuff release in all groups. FMD was greater among non-smoking pregnant women compared to smoking pregnant women (11.50 +/- A 5.77 vs. 8.74 +/- A 4.83; p = 0.03) and also between non-smoking non-pregnant women compared to smoking non-pregnant women (10.52 +/- A 4.76 vs. 7.21 +/- A 5.57; p = 0.03). Maximum FMD was observed approximately 60 s after stimulus in all groups regardless of smoking and pregnancy status. The smoking habit seems to lead to endothelial dysfunction both in pregnant and non-pregnant women, as demonstrated by the lower FMD in smokers.

Genetic associations between age at first calving and heifer body weight and scrotal circumference in Nelore cattle

P>Age at first calving (AFC) measures the entry of heifers into the beef cattle production system. This trait can be used as a selection criterion for earlier reproductive performance. Using data from Nelore cattle participating in the `Program for Genetic Improvement of the Nelore Breed` (PMGRN-Nelore Brazil), bi-trait analyses were performed using the restricted maximum likelihood method, based on an AFC animal model and the following traits: female body weight adjusted to 365 (BW365) and 450 (BW450) days of age, and male scrotal circumference adjusted to 365 (SC365), 450 (SC450), 550 (SC550) and 730 (SC730) days of age. The heritability estimates for AFC ranged from 0.02 +/- 0.02 to 0.04 +/- 0.02. The estimates of additive direct heritabilities (with standard error) for BW365, BW450, SC365, SC450, SC550 and SC730 were 0.36 +/- 0.07, 0.38 +/- 0.07, 0.48 +/- 0.07, 0.65 +/- 0.07, 0.64 +/- 0.07 and 0.42 +/- 0.07, respectively, and the genetic correlations with AFC were -0.38, -0.33, 0.10, -0.13, -0.13 and 0.06, respectively. In the herds studied, selection for SC365, SC450, SC550 or SC730 should not cause genetic changes in AFC. Selection based on BW365 or BW450 would favor smaller AFC breeding values. However, the low magnitude of direct heritability estimates for AFC in these farms indicates that changes in phenotypical expression depend mostly on non-genetic factors.

Effects of gonadotropin-releasing hormone at initiation of the 5-d timed artificial insemination (AI) program and timing of induction of ovulation relative to AI on ovarian dynamics and fertility of dairy heifers

Two experiments evaluated the effects of the first GnRH injection of the 5-d timed artificial insemination (AI) program on ovarian responses and pregnancy per AT (P/AI), and the effect of timing of the final GnRH to induce ovulation relative to AT on P/AI. In experiment 1, 605 Holstein heifers were synchronized for their second insemination and assigned randomly to receive GnRH on study d 0 (n = 298) or to remain as untreated controls (n = 307). Ovaries were scanned on study d 0 and 5. All heifers received a controlled internal drug-release (CIDR) insert containing progesterone on d 0, a single injection of PGF(2 alpha),, and removal of the CIDR on d 5, and GnRH concurrent with timed AT on d 8. Blood was analyzed for progesterone at AI. Pregnancy was diagnosed on d 32 and 60 after AI. Ovulation on study d 0 was greater for GnRH than control (35.4 vs. 10.6%). Presence of a new corpus luteum (CL) at PGF(2 alpha),, injection was greater for GnRH than for control (43.1 vs. 20.8%), although the proportion of heifers with a CL at PGF(2 alpha) did not differ between treatments and averaged 87.1%. Progesterone on the day of AT was greater for GaRH than control (0.50 +/- 0.07 vs. 0.28 +/- 0.07 ng/mL). The proportion of heifers at AI with progesterone <0.5 ng/mL was less for GURH than for control (73.8 vs. 88.2%). The proportion of heifers in estrus at AI did not differ between treatments and averaged 66.8%. Pregnancy per AI was not affected by treatment at d 32 or 60 (GnRH = 52.5 and 49.8% vs. control = 54.1 and 50.0%), and pregnancy loss averaged 6.0%. Responses to GnRH were not influenced by ovarian status on study d 0. In experiment 2, 1,295 heifers were synchronized for their first insemination and assigned randomly to receive a CIDR on d 0, PGF(2 alpha) and removal of the CIDR on d 5, and either GnRH 56 h after PGF(2 alpha) and AI 16 h later (OVS56, n = 644) or GnRH concurrent with AI 72 h after PGF(2 alpha) (COS72; n = 651). Estrus at AI was greater for COS72 than for OVS56 (61.4 vs. 47.5). Treatment did not affect P/AI on d 32 in heifers displaying signs of estrus at AI, but COS72 improved P/AI compared with OVS56 (55.0 vs. 47.6%) in those not in estrus at AI. Similarly, P/AI on d 60 did not differ between treatments for heifers displaying estrus, but COS72 improved P/AI compared with OVS56 (53.0 vs. 44.7%) in those not in estrus at AI. Administration of GnRH on the first day of the 5-d timed AI program resulted in low ovulation rate and no improvement in P/AI when heifers received a single PGF(2 alpha) injection 5 d later. Moreover, extending the proestrus by delaying the finAI GnRH from 56 to 72 h concurrent with AI benefited fertility of dairy heifers that did not display signs of estrus at insemination following the 5-d timed AI protocol.

Effects of flunixin meglumine, recombinant bovine somatotropin and/or human chorionic gonadotropin on pregnancy rates in Nelore cows

The objective was to compare pharmacological strategies aiming to inhibit prostaglandin F2 alpha (PGF(2 alpha)) synthesis (flunixin meglumine; FM), stimulate growth of the conceptus (recombinant bovine somatotropin; bST) and progesterone (P(4)) synthesis (human chorionic gonadotropin; hCG), as well as their combinations, regarding their ability to improve pregnancy rates in beef cattle. Lactating Nelore cows (N = 975), 35 to 70 days postpartum, were synchronized and inseminated by timed artificial insemination (TAT) on Day 0. On Day 7, cattle were allocated into eight groups and received one of the following treatments: saline (S) on Days 7 and 16 (Group Control); S on Day 7 and FM on Day 16 (Group FM); bST on Day 7 and S on Day 16 (Group bST); bST on Day 7 and FM on Day 16 (Group bST + FM); hCG on Day 7 and S on Day 16 (Group hCG); hCG on Day 7 and FM on Day 16 (Group hCG + FM); bST and hCG on Day 7 and S on Day 16 (Group bST + hCG), or bST and hCG on Day 7 and FM on Day 16 (Group bST + hCG + FM). The aforementioned treatments were administered at the following doses: 2.2 mg/kg FM (Banamine (R); Intervet Schering-Plough, Cotia, SP, Brazil), 500 mg bST (Boostin (R); Intervet Schering-Plough), and 2500 IU hCG (Chorulon (R); Intervet Schering-Plough). Pregnancy diagnosis was performed 40 days after TAI by transrectal ultrasonography. Pregnancy rates were not significantly different among treatments. However, there was a main effect of hCG treatment to increase pregnancy rates (63.0 vs. 55.4%; P = 0.001). Concentrations of P(4) did not differ significantly among groups on Day 7 or on Day 16. However, consistent with the higher pregnancy rates, hCG increased P(4) concentrations on Day 16 (10.6 vs. 9.6 ng/mL, respectively; P = 0.05). We concluded that hCG treatment 7 days after TAI improved pregnancy rates of lactating Nelore cows, possibly via a mechanism leading to induction of higher P(4) concentrations, or by reducing the luteolytic stimulus during maternal recognition of pregnancy. (C) 2011 Elsevier Inc. All rights reserved.

Pulmonary Maturation in Canine Foetuses From Early Pregnancy to Parturition

Development of the foetal respiratory system includes both pulmonary growth and maturation. In human medicine, a higher incidence of respiratory distress is reported in newborn males. This study aimed to identify different phases of canine foetal lung maturation throughout pregnancy, to determine the stage of pregnancy in which surfactant production begins and to compare pulmonary development of male and female foetuses. Pregnant bitches (34) were subjected to elective ovariohysterectomy and allocated into four groups, according to the stage of pregnancy: 30-40 days of pregnancy (n = 10), 41-50 days (n = 10), 51-60 days (n = 10) and bitches in the first stage of parturition (n = 4). Foetal lungs were histologically processed and evaluated by optical microscopy. The pseudoglandular phase was identified between the 35th day and 46th day of gestation; the onset of canalicular and saccular periods was observed, respectively, from the 48th day and 60th day of pregnancy. Lungs from foetuses at term were in the saccular phase; thus, the development into the alveolar period occurs in the neonatal period. The histological analyses revealed that respiratory tract development is centrifugal, from upper to lower airways. Therefore, it is possible to identify distinct development periods in different portions of the same organ. In conclusion, the saccular phase of lung development begins around 57 and 60 days of pregnancy, the period in which surfactant production is believed to occur. Male and female foetuses present similar pulmonary development from early pregnancy until parturition.

Vitamin D receptor haplotypes affect lead levels during pregnancy

Pregnant women are particularly susceptible to toxic effects associated with lead (Pb) exposure. Pb accumulates in bone tissue and is rapidly mobilized from bones during pregnancy, thus resulting in fetal contamination. While vitamin D receptor (VDR) polymorphisms modify bone mineralization and affect Pb biomarkers including blood (Pb-B) and serum (Pb-S) Pb concentrations, and %Pb-S/Pb-B ratio, the effects of these polymorphisms on Pb levels in pregnant women are unknown. This study aimed at examining the effects of three (Fokl, Bsml and Apal) VDR polymorphisms (and VDR haplotypes) on Pb levels in pregnant women. Pb-B and Pb-S were determined by inductively coupled plasma mass spectrometry in samples from 256 healthy pregnant women and their respective umbilical cords. Genotypes for the VDR polymorphisms were determined by PCR and restriction fragment length digestion. While the three VDR polymorphisms had no significant effects on Pb-B, Pb-S or %Pb-S/Pb-B ratio, the haplotype combining the f, a, and b alleles for the Fokl, Apal and Bsml polymorphisms, respectively, was associated with significantly lower Pb-S and %Pb-S/Pb-B (P<0.05). However, maternal VDR haplotypes had no effects on Pb levels in the umbilical cords. To our knowledge, this is the first study showing that a combination of genetic polymorphisms (haplotype) commonly found in the VDR gene affects Pb-S and %Pb-S/Pb-B ratios in pregnant women. These findings may have major implications for Pb toxicity because they may help to predict the existence of a group of subjects that is genetically less prone to Pb toxicity during pregnancy. (C) 2010 Elsevier B.V. All rights reserved.