Serum concentrations of androstenediol and androstenediol sulfate, and their relation to cytokine production during and after normal pregnancy

Since it is known that androstenediol (ADIOL) has potent immunoregulatory effects, changes in ADIOL levels during and after pregnancy might affect the maternal immune system. We examined serum concentrations of ADIOL and androstenediol 3-sulfate (ADIOLS) together with IFN-gamma and IL-4 production levels during pregnancy and after delivery up to 10-11 months postpartum. The subjects were 73 normal pregnant, 76 normal postpartum, and 28 normal non-pregnant women. ADIOL and ADIOLS were measured using EIA and GC/MS, respectively. The cytokine levels in the supernatant of whole-blood cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin were measured using ELISA. ADIOL levels significantly decreased compared to non-pregnant levels in the first trimester (P < 0.05) and were reversed in the third trimester (P < 0.05). After pregnancy, ADIOL levels gradually declined, and a significant decrease was observed at 10-11 months postpartum (P < 0.05). ADIOLS levels were significantly lower in the third trimester (P < 0.05) and significantly higher at the first month postpartum (P < 0.001) compared to non-pregnant women. IFN-gamma and IL-4 levels decreased during pregnancy and subsequently increased postpartum. On the other hand, we found significant negative correlations between ADIOL concentrations and production levels of IFN-gamma (P < 0.05) or IL-4 (P < 0.05). These findings suggest that ADIOL may be involved in modifying the maternal immune response during and after pregnancy.     

Hormonal and experiential predictors of infant survivorship and maternal behavior in a monogamous primate (Callicebus cupreus)

To better understand the roles that hormones and experience play in infant survival and maternal behavior in a biparental primate species, we analyzed urinary estrone (E(1)C) and pregnanediol glucuronide (PdG) from 24 socially housed titi monkey (Callicebus cupreus) females over 54 pregnancies (N = 1,430 samples). Pregnancies were categorized according to whether the infant survived (N = 35) or not (N = 19), and by maternal parity (primiparous: N = 9; multiparous: N = 45). Mothers of infants that survived had a significantly greater drop in PdG from the third trimester to the first week postpartum than mothers of infants that did not survive. Multiparous mothers had a greater increase in PdG from the first to the third trimester as well as greater increases in the E(1)C:PdG ratio from the first to the third trimester and from the third trimester to the first week postpartum. There were positive relationships between third trimester PdG and maternal carrying and nursing during the first week postpartum, and between maternal age and carrying during the infant's first month of life. There was a negative correlation between maternal age and PdG during the third trimester. These results suggest that elevated progesterone during late pregnancy followed by progesterone withdrawal immediately following parturition is associated with greater probability of infant survivorship and maternal behavior in this species, and that older females engage in more postpartum maternal care.     

Productive performance of beef cows subjected to different nutritional levels in the third trimester of gestation

In general, calf production occurs in less intensive systems. The limitation of nutrients during the gestation phase of beef cows can have negative impacts on the consequent productivity of females. Therefore, this study aimed to evaluate the effects of nutritional levels in the third trimester of pregnancy on the productive performance of beef cows kept in a natural pasture (NP). Eighty-three Charolais × Nelore cows were used, ranging in age from 4 to 12 years, which were divided according to their nutritional levels during the third trimester of pregnancy: NP, cows supplemented with 100% of their energy and protein requirements (SP100) and cows supplemented with 150% of their energy and protein requirements (SP150). The experimental design was completely randomized with three treatments and a varied number of repetitions. The SP100 and SP150 cows presented better body condition at calving (2.92 and 2.99 vs 2.81 points) and at the start of the breeding season (2.90 and 2.95 vs 2.80 points) than did NP cows. The nutritional level of the cows in the third trimester of gestation did not influence the blood metabolite concentrations. The plasma levels of albumin and total proteins were 3.11 and 8.18 g/dl, respectively. Glucose and cholesterol showed values of 74.96 and 166.50 mg/dl. The lowest concentration of blood metabolites was observed in the first postpartum weeks. The SP100 and SP150 cows showed faster follicular growth and, consequently, a higher percentage of females with ovulatory follicles at 21 days postpartum than did NP cows (45.68, 41.11, and 11.00%, respectively). The SP150 cows had a higher pregnancy rate (40.74%), total calf production (295.88 kg/cow), and consequently, offspring sale value. An increased nutritional level in the third trimester of pregnancy improves the postpartum metabolic condition and productive efficiency of beef cows kept on NP.     

Atrial natriuretic factor in pregnancy and pregnancy-induced hypertension.

In normal pregnancy, cross-sectional clinical data do not consistently show plasma ANF concentration differences between early pregnancy and the nonpregnant state. Sequential data in the baboon (but not in rat) show a significant decrease in plasma ANF concentration and in cardiac filling pressures in early pregnancy. The latter data support the view that pregnancy is an underfill state secondary to a primary vasodilatation. Cross-sectional and longitudinal studies in normal pregnancy in humans show that plasma ANF levels tend rise to values that are, in the third trimester, higher than in the nonpregnant state. However, late postpartum sequential data (1.5-3 months) in humans do now show a significant drop in plasma ANF concentrations, suggesting that plasma ANF is not actually increased in normal pregnancy. In the baboon (but not in the rat) there is a steady rise in plasma ANF levels to values that are significantly higher in third trimester than before pregnancy. These data suggest that in human pregnancy, in contrast with the baboon, the plasma volume expansion induced by normal pregnancy is not sensed as such by the atria probably because of an isopressive adaptation of plasma volume to an enlarged vascular bed. However, acute decrease or increase of venous return induced by low sodium diet, changing position or infusion of isotonic saline are sensed as such by the atria in normal pregnancy as in the nonpregnant state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal thyroid function in early and late pregnancy.

Thyroid function was investigated during and after pregnancy in 12 healthy euthyroid women. During pregnancy, serum total T4 (TT4) levels were significantly elevated and nearly stable, while thyroxine-binding globulin (TBG) levels progressively increased till the 7th month. A slight elevation, though not significant, of free T4 (fT4) was recorded in early pregnancy. In the following months, fT4, free T3 (fT3) and the T4/TBG ratio progressively diminished, reaching a plateau at the 7th month. Serum TSH levels, measured by an ultrasensitive immunofluorometric assay, were comparable to postpartum values during the first trimester and showed a moderate upward trend with the progression of pregnancy. The evaluation of 24-hour TSH profiles was performed in 5 women during the first trimester of pregnancy. In all women, the circadian rhythm of TSH was present with a normal nocturnal surge, though anticipated in 1 case. In summary (1) during the first trimester of pregnancy, the increased thyroid activity does not seem to be only sustained by pituitary TSH which remains unmodified; the negative correlation between TSH and hCG levels might suggest that hCG also stimulates the gland to increase thyroid hormone output, and the presence of a normal TSH circadian rhythm indicates that the central mechanism of neuroregulation of the pituitary-thyroid axis is preserved in early pregnancy, and (2) in late pregnancy, a marked decrease in free thyroid hormone fractions is accompanied by serum TSH levels still in the normal range, indicating a modification of thyroid homeostasis which might recognize various etiological factors.     

Glycated albumin and glycated hemoglobin levels in normal pregnancy

Glycated albumin levels showed a progressive increase during normal pregnancy. The mean values (mole hexose/mole protein) were 1.68 +/- 0.27 (n = 15) in nonpregnant women, 1.83 +/- 0.21 (n = 11) in first trimester, 2.00 +/- 0.41 (n = 13) in second trimester, and 2.42 +/- 0.49 (n = 15) in third trimester. Glycated hemoglobin levels indicated a biphase pattern with low values at midpregnancy (controls 0.29 +/- 0.05, first trimester 0.30 +/- 0.04, second trimester 0.27 +/- 0.05, and third trimester 0.33 +/- 0.04). The data suggest that glycated albumin reflects the decreased glucose tolerance in pregnancy better that glycated hemoglobin levels. The reasons for the differing pattern of the two glycated proteins are discussed.     

Serum Fibrin Degradation Products Throughout Normal Pregnancy

Fibrin/fibrinogen degradation products in the serum of 169 healthy pregnant and 43 healthy non-pregnant subjects of a similar age group showed a significant increase throughout pregnancy, the highest levels being obtained in the third trimester. There was no correlation with plasma fibrinogen levels or euglobulin lysis times. Though these changes may be due to other alterations in pregnancy not primarily associated with fibrinolysis, it is possible that actual fibrinolysis is not decreased in late pregnancy, as has been previously asssumed.     

Detection of immunoreactive human placental oxytocin and its contractile effect on the uterine muscle

Freshly obtained human placentas from various periods of gestation were quantitatively analysed for their immunoreactive oxytocin (OT) content and its biological activity was examined in a Magnus apparatus by utilizing rat uterus. The mean values for placental immunoreactive OT per gram tissue increased from the first to the second trimester, maintaining its high level to term. The total content of placental OT also increased continually from the beginning of pregnancy to term. Blood levels of estrogen stimulated neurophysin (ESN) and OT were concomitantly enhanced through gestation. Placental extract and synthetic OT showed similar peaks in the elution pattern of ion-exchange chromatography through a carboxymethyl cellulose column. Synthetic OT and placental extract induced marked uterine contraction in diestrous rats. However placental extract previously incubated with OT antiserum failed to induce this effect. Though detection of immunoreactive OT by immunoassay alone does not provide definite identification of pituitary and placental OT, the present study suggests that placental immunoreactive OT could have a contracting effect on the uterine muscle.     

Serum PGF2 alpha levels during late pregnancy, labour and the puerperium

The serum prostaglandin (PG) F2alpha levels of women in the last trimester of pregnancy have been measured and compared with the levels found in samples taken during labor, during the 1st week postpartum, and from nonpregnant women. The laboratory procedures for drawing the samples and making the radioimmunoassay measurements are explained. 40 samples were taken during late pregnancy, 46 during labor, 7 during the 1st week postpartum, and 8 from nonpregnant women. The results are graphed. PGF2alpha levels during late pregnancy resemble those found in nonpregnant women. A significant rise (p.05) occurs during labor, most markedly during the late 1st stage. Levels during the 1st week postpartum were found to be very low. There was no difference between serum levels during the 33rd-36th weeks and those found during weeks 34-40. Serum levels did not differ according to whether labor was spontaneous, induced by artificial rupture of fetal membranes and infusion of Syntocinon, or merely accelerated by syntocinon infusion. This indicates that PG release occurs as a result of labor rather than as a triggering mechanism for the onset of labor. The highest levels of serum PGF2alpha seem to be associated with the time of greatest uterine activity and the period of greatest cervical stretching.     

The effect of Trypanosoma vivax infection on late pregnancy and postpartum return to cyclicity in Boran cattle

A study was designed to examine the effect of infection with Trypanosoma vivax KETRI 2501 on the maintenance of pregnancy and postpartum return to reproductive function in susceptible Galana (n = 6) and trypano-tolerant Orma Boran (n = 6) heifers during the third trimester of pregnancy. Of the 12 study animals, 3 Galana and 3 Orma Boran heifers served as controls. One of 3 Galana heifers calved prematurely with subsequent perinatal loss. Of the 2 heifers that produced live calves, 1 calf died shortly after birth, while the other survived. Two of 3 Orma heifers calved prematurely and all 3 calves died shortly after birth. The 6 control heifers produced live calves at term, all of which survived. Infection with T. vivax during the third trimester of pregnancy delayed the resumption of ovarian activity after calving, with the Ormas taking a significantly (P < 0.05) shorter time from calving to ovulation. There was no clear evidence that premature birth was associated with pathological changes in reproductive organs. Results from this study demonstrated that infection with pathogenic T. vivax during late pregnancy influenced the outcome of pregnancy in both susceptible Galana and trypano-tolerant Orma Boran heifers, resulting in premature births, perinatal loss, retained placentae, low birth weights and a prolonged period to the onset of postpartum ovarian activity.     

Effects of the reproductive status in Zebu heifers on the immunoglobulin M and G levels in bovine Trypanosoma vivax infection

Immunoglobulin M and G levels in bovine Trypanosoma vivax infection were compared in non-pregnant, first, second and third trimester pregnant heifers. All the infected heifers showed a significant rise in IgM levels when compared to the non-infected controls. 7–8 fold increases were recorded. There were however differences in the rate of increases and ability to maintain peak level response (P <0.01) between the groups. Infected pregnant heifers in the first and second trimester responded better than infected non-pregnant and infected heifers in the third trimester pregnancy. In all the groups, the differences between the infected and control heifers were highly significant (P <0.001). The IgG levels showed a similar pattern of increases in infected heifers though response was gradual. In the different groups 1.4–2.5-fold increases were recorded. These were significantly different from levels in the control (P <0.01). Again, pregnant heifers responded better than non-pregnant heifers except those in the third trimester pregnancy. The results correlated with the observation that given the same conditions, clinical manifestation of T. vivax infection is more severe in non-pregnant than in pregnant heifers except those in advanced pregnancy.     

Spatial working memory and hippocampal size across pregnancy in rats

The present experiments investigated the effects of pregnancy on performance in the Morris water maze and on hippocampal volume. In the first study, pregnant rats (in between the first and second trimester) outperformed nonpregnant rats on the Morris water maze on 1 day of testing. In the second study, rats were tested in a working memory variation of the maze in which the spatial location of the platform varied. Pregnant females traveled shorter distances than nonpregnant females during the first two trimesters, but performed worse than nonpregnant females during the third trimester. Latency measures showed a similar profile. Group differences in performance were not related to changes in swim speed. However, changes in performance in pregnant females may be related to estrogen, progesterone, and/or corticosterone levels during pregnancy, with low levels of estradiol and high levels of progesterone being associated with better performance. There were no significant differences between pregnant and nonpregnant animals on any of the brain measures, although pregnant animals tended to have a smaller hippocampus than nonpregnant animals. These results indicate that pregnancy can affect performance, possibly related to the hormonal changes that accompany pregnancy.     

孕中晚期HCG、D-二聚体变化与妊娠结局相关性

HCG是由胎盘的滋养层细胞分泌的一种糖蛋白,其测定可应用于诊断异位妊娠、先兆流产、葡萄胎及妊娠滋养细胞肿瘤（GTN）等不良妊娠结局。HCG水平可用于预测子痫前期一子痫、流产等。D-二聚体是交联的纤维蛋白被纤溶酶水解后产生的一种特异性分子标志物,是继发性纤溶的重要指征,对诊断血栓性疾病具有重要意义。孕妇D-二聚体与妊娠期高血压疾病、产后大出血、妊娠合并心脏病等有关。为了探讨妊娠中、晚期HCG、D-二聚体变化对妊娠结局的影响,通过复习国内外文献,分析孕中、晚期HCG、D2聚体变化与妊娠结局的相关性．为临床预测妊娠结局提供临床依据。     

Serum thyroglobulin concentration in normal pregnancy

We measured the levels of serum thyroglobulin (Tg) in 52 pregnant females at various stages and compared them with those of 15 age-matched nonpregnant females. Serum Tg was measured by a solid-phase immunoradiometric assay. In pregnant females, mean serum Tg levels at the first, second, early third, and late third trimesters were 8.4 (range; 1.3-18.0), 9.2 (1.7-25.6), 10.1 (1.8-22.8), and 12.1 ng/ml (5.3-25.2), respectively. The statistical comparison was made after logarithmic transformation of the data. The mean value only at the late third trimester was significantly higher than that of controls (mean; 6.0 ng/ml, range; 1.5-23.6), but each value was within the normal range. Although serum Tg levels have been reported to be high at the end of pregnancy, our results indicate that the Tg levels in females could be clinically interpreted without regard to the coexistence of pregnancy.     

The effects of oxidative stress in urinary tract infection during pregnancy

The purpose of this study was to determine the effect of urinary tract infection (UTI) on antioxidant systems and lipid peroxidation (LPO) levels during pregnancy. We also investigated if these antioxidant systems and LPO levels differed in each trimester. One hundred forty-three nonpregnant women, as a control group, and 77 pregnant women were included in the study. Urine cultures were performed according to standard techniques. Catalase (CAT), superoxide dismutase (SOD), and LPO levels were measured using a spectrophotometer. UTI was observed in 14 of 77 pregnant women and the isolated microorganisms were Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus. CAT, SOD, and LPO levels were increased in pregnant women compared with nonpregnant women (P<.01). CAT, SOD activities, and LPO levels were increased from the first trimester to the third trimester in pregnancy without UTI. However, CAT and SOD activities were decreased, LPO levels were increased from the first trimester to the third trimester in pregnancy with UTI (P<.01). Pregnancy causes oxidative stress and also UTI during pregnancy may aggravate oxidative stress.     

Influence of oxidative stress and metabolic adaptation on PON1 activity and MDA level in transition dairy cows

Serum PON1 is a HDL-associated enzyme that protects lipoproteins, both LDL and HDL, against oxidation and it is considered as an antioxidative/anti-inflammatory component of HDL. Dairy cows are highly susceptible to oxidative stress which commonly occurs in late pregnancy and early lactation. During the transition period, increased production of reactive oxygen species is associated to processes of metabolic adaptation to a low-energy balance. We investigated serum paraoxonase-1 (PON1) activity and malondialdehyde (MDA) concentration to assess the antioxidative/prooxidative status during pregnancy and the postpartum period. In order to evaluate metabolic homeostasis, common metabolic parameters (glucose, triglyceride, total cholesterol, HDL-C and albumin concentrations) were determined as well. A significantly lower PON1 activity was found in late pregnancy and early postpartum (P<0.05) compared to the first and the second trimester of pregnancy and the mid-lactation. MDA level was significantly higher (P<0.05) in the dry period compared to pregnant lactating and postpartum cows. Serum glucose concentration (P<0.001) was lower in the early and late puerperium indicating low-energy balance in the early lactation. Serum triglyceride and albumin concentrations were lower in late puerperium (P<0.001), while total cholesterol and HDL-C were lower during the dry period (P<0.05) as well as in early postpartum (P<0.001). Significant correlations of PON1 activity with glucose (P<0.05), albumin (P<0.05), total cholesterol (P<0.001) and HDL-C (P<0.001) were also found. The observed lower serum PON1 activity and higher MDA level in late pregnancy and early postpartum could indicate a prooxidants/antioxidants imbalance influenced by reproductive stress and metabolic adaptation in the transition period of dairy cows.     

Pregnancy suppresses experimental autoimmune encephalomyelitis through immunoregulatory cytokine production

Women with multiple sclerosis (MS) often experience a decrease in relapse rate during pregnancy, most notably during the third trimester, with a flare of disease activity 3-6 mo postpartum. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have shown that pregnancy delays the onset and decreases the incidence of disease. We investigated the effect of pregnancy and the postpartum period in a remitting-relapsing model of murine EAE. When immunization occurs during pregnancy, mice show a reduction in the incidence of EAE as well as a decrease in clinical severity, while mice immunized during the postpartum period exhibit more severe disease. No differences in lymphocyte proliferation or expression of activation markers were noted when immunization occurred during pregnancy as compared with the nonpregnant controls. Mice immunized during pregnancy produced less TNF-alpha and IL-17, and showed an increased number of IL-10-secreting cells within the CD11b+, CD11c+, CD19+, and CD4+/CD25+ populations. No differences were noted in the production of IFN-gamma, IL-2, IL-4, and IL-5. These results suggest that when an Ag is introduced during pregnancy, an immunoregulatory rather than an immunosuppressive or Th2 environment predominates.     

Impact of BVDV infection of white-tailed deer during second and third trimesters of pregnancy

While it has been demonstrated that persistent bovine viral diarrhea virus (BVDV) infections can be established in white-tailed deer (Odocoileus virginianus) following in utero exposure in the first trimester of gestation, there is little to no information regarding the outcome of infection in later stages of pregnancy in deer. Our goal was to observe the impact of infection of white-tailed deer in the second and third trimesters of pregnancy. Five white-tailed deer in the second trimester of pregnancy and four in the third trimester were infected with a BVDV type 2 virus previously isolated from a BVDV-infected deer harvested from the wild. Infection of deer in the second trimester of pregnancy resulted in loss of the pregnancy in three of five deer. Fawns born to the two remaining deer appeared normal and were born BVDV antigen-negative with neutralizing serum antibodies against BVDV. Infection of does in the third trimester of pregnancy did not result in fetal death or persistent infection and all does gave birth to live, healthy fawns that were BVDV antigen-negative and born with antibodies against BVDV. These results, combined with those previously reported regarding BVDV infection in the first trimester of pregnancy, suggest that the impact of BVDV infection of pregnant white-tailed deer is very similar to that observed in pregnant cattle.     

Plasma copper concentrations in pathological pregnancies.

Copper is an essential element required for the formation of many enzymes with important roles in the human body. During pregnancy, the maternal serum copper concentration is increased due to the higher levels of ceruloplasmin that are the result of elevated oestrogen levels. The aim of this work was to investigate maternal plasma copper concentrations in relation to various pathological conditions during pregnancy. A total of 319 maternal plasma samples were analysed: 103 taken from women in the first trimester, 73 in the second trimester, 99 in the third trimester of pregnancy and 44 at delivery. The plasma concentration of copper during each trimester of normal pregnancy was taken as a reference value. Group comparisons performed by analysis of variance (ANOVA) followed by Dunnett test indicated substantially lower plasma concentrations of copper in pathological conditions diagnosed during the first trimester of pregnancy (spontaneous abortion, threatened abortion, missed abortion and blighted ovum). No significant differences in maternal plasma blood copper concentrations were found in pathological conditions (threatened abortion, threatened preterm delivery and pyelonephritis) diagnosed in the second trimester of pregnancy. Significant differences in plasma copper concentrations were found in the third trimester, for which finding the Dunnett test indicated the cholestasis group to be responsible. Except for twin pregnancy, a tendency to higher plasma copper concentrations, however not statistically significant, was observed in other pathological conditions during the third trimester (gestosis, intrauterine growth retardation, preterm labour).     

Diminished maternal responsiveness during pregnancy in multiparous female common marmosets

Common marmoset monkeys (Callithrix jacchus) live in small groups in which, usually, only a single female breeds and all group members provide infant care. When two females breed concurrently, however, they may commonly kill one another's infants, especially during the peripartum period. To investigate the mechanisms underlying infanticide by breeding females, we characterized responses of multiparous females to infants and determined circulating hormone levels in adult females during early pregnancy, late pregnancy, and the early postpartum period. Additionally, we compared the responses of postpartum females to their own infants and infants of other females (unfamiliar infants). Postpartum females were highly maternal toward both their own and unfamiliar infants, and showed no differences in their behavioral or hormonal responses to the two. During both early and late pregnancy, however, these females exhibited longer latencies to initially approach unfamiliar infants and spent less time carrying unfamiliar infants. Moreover, females spent less time carrying unfamiliar infants during late pregnancy than early pregnancy. Most late pregnant females never carried infants, and those that did rejected them quickly. Prolactin concentrations were higher and progesterone concentrations lower postpartum than in early or late pregnancy, while estradiol concentrations, the estradiol-to-progesterone ratio, and cortisol levels were higher during late pregnancy. Within reproductive conditions, however, maternal behaviors were not correlated with hormone levels. These results suggest that maternal responsiveness in marmosets may be attenuated during pregnancy, especially late pregnancy, and this may contribute to infanticide by breeding females.