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Biomedical subjects

G E Mann

Publications and source records attributed to G E Mann.

At least 37 records · Page 2Linked to original sources
PubMed2003

Attenuation of PGF2alpha release in ewes infused with the oxytocin antagonist L-368,899.

We have investigated the effects of systemic administration of the oxytocin antagonist (OTA) L-368,899 on luteolytic PGF(2alpha) release in ewes. In the first study, carried out in four ovariectomized ewes primed with progesterone to induce responsiveness to oxytocin, 3-h i.v. infusions of 3, 10 and 30 microg/kg/min OTA, carried out on days 12, 14, 16 and 18 in a Latin Square design, resulted in a significant attenuation of the oxytocin induced increase in PGFM concentration at all doses (OTA 139+/-8.3% of pre-oxytocin baseline; control 206.8+/-18.7%; P<0.005). In a further study, continuous infusion of cyclic ewes (n=6) with 10 microg/kg/min OTA from day 13 to day 17 of the cycle resulted in a reduction in both the frequency (OTA 1.0+/-0.4/ewe; control 2.2+/-0.2/ewe; P<0.05) and amplitude (OTA 31.8+/-11.0 pg/ml; control 68.8+/-10.4 pg/ml; P<0.05) of endogenous PGFM episodes compared to control ewes (n=5) measured during daily 8-h sampling windows on days 14-17. This reduction in PGFM concentrations was accompanied by a modest extension in the day of luteolysis (progesterone <0.5 ng/ml) to day 17.5+/-0.4 in the OTA treated group compared with day 16.4+/-0.5 in the control group (P=0.07). The results demonstrate that treatment with OTA caused a significant reduction in episodes of increased PGFM concentration during the period of luteolysis and may provide an approach by which to reduce early pregnancy failure.

Animals↗
PubMed2003

Follicle growth, corpus luteum function and their effects on embryo development in postpartum dairy cows.

Absent or irregular ovarian cycles in lactating dairy cows are caused by failure to ovulate the dominant follicle at the appropriate time. The follicle then either regresses or develops into a cyst. This process can be triggered by a variety of metabolic and disease factors that act at the hypothalamus and pituitary gland to inhibit pulsatile LH secretion and the LH surge, and at the ovary to reduce follicular growth and oestradiol production. Cows of poor energy status have low circulating concentrations of insulin-like growth factor I (IGF-I). Predisposing factors include calving difficulties, inappropriate diet, reduced intake of dry matter and a high rate of body condition score loss. Various stressors predispose the follicle to cyst development by inhibiting the LH surge and ovulation; these include common infections, such as mastitis. Even when ovulation does occur, poor follicular development may result in production of an inadequate corpus luteum. The timing of the increase in progesterone in the early luteal phase (days 4-5) appears to be a key determinant of fertility, probably because it alters the secretory activity of the reproductive tract, thus influencing embryonic growth and interferon-tau production. A period of negative energy balance after calving can reduce fertility even though metabolic parameters have apparently improved at the time of service.

Animals↗
PubMed2002

Increased nitric oxide synthesis in uraemic platelets is dependent on L-arginine transport via system y(+)L.

Bleeding tendency in uraemic patients seems to be related to alterations in the activity of the L-arginine-nitric oxide (NO) signalling pathway in platelets. We have reported previously that L-arginine influx into human platelets is mediated by the high-affinity cationic amino acid transport system y(+)L. In the present study we examined the dependency of nitric oxide synthase (NOS) activity on L-arginine transport in platelets isolated from healthy controls and uraemic patients on haemodialysis. We investigated basal and ADP-stimulated NOS activity, as reflected by the conversion of L-[(3)H]arginine to L-[(3)H]citrulline, in platelets obtained from healthy controls and uraemic patients on haemodialysis. To determine whether NOS activity depended on L-arginine transport, we analysed the effects of competitive inhibitors of L-arginine transport via system y(+)L on NOS activity. Basal NOS activity was increased from 0.21+/-0.06 to 0.7+/-0.2 pmol/10(8) platelets ( n=9, P<0.05) in uraemic patients. Stimulation by ADP (10 micro M) significantly increased NOS activity (inhibitable by L-NAME) in control platelets (252%) but failed to increase further the elevated NOS activity in uraemic platelets. Homocysteine and L-leucine, competitive inhibitors of system y(+)L, markedly inhibited NOS activity in uraemic platelets. These observations indicate that platelets from uraemic patients on haemodialysis generate more NO than control platelets and that entry of L-arginine via system y(+)L is most likely rate-limiting for platelet NO production in chronic renal failure.

Adenosine Diphosphate↗
PubMed2002

Activation of L-arginine transport in peripheral blood mononuclear cells in chronic renal failure.

Transport of LL-arginine, the precursor for nitric oxide (NO) synthesis, has been investigated in human peripheral blood mononuclear cells (PBMCs) obtained from healthy volunteers and chronic renal failure patients. Chronic renal failure patients were either on treatment by haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Saturable influx of L-arginine in PBMCs was mediated by the cationic amino acid transport systems y(+) and y(+)L. Initial rates of L-arginine transport (2 microM) via system y(+) were significantly increased in chronic renal failure patients, whereas transport via system y(+)L was unaffected. The increase in L-arginine transport via system y(+) was: 1.7-fold in uraemic patients on CAPD, 4.3-fold in uraemic patients pre-haemodialysis and 2.6-fold post-haemodialysis. When the intracellular PBMCs amino acid profile was analysed in chronic renal failure patients and control subjects, L-lysine and L-arginine concentrations were significantly increased in pre-haemodialysis uraemic patients and restored to normal values by haemodialysis and CAPD. The present study provides the first evidence that system y(+) mediates the increased transport of L-arginine in PBMCs from patients with chronic renal failure. The increased activity of system y(+) may provide the necessary supply of L-arginine to sustain NO synthesis in PBMCs exposed to increased levels of circulating cytokines in chronic renal failure.

Amino Acids↗
PubMed2002

Milk production and composition, ovarian function, and prostaglandin secretion of dairy cows fed omega-3 fats.

Four multiparous Holstein cows were used in a 4 x 4 Latin square experiment to study the effects of fat sources rich in omega-3 fatty acids on milk production and composition, follicular development, and prostaglandin secretion. All cows were fed a total mixed diet containing 60% grass silage and 40% concentrate. The four treatments were concentrates based either on Megalac, formaldehyde-treated whole linseed, a mixture (50:50, oil basis) of fish oil and formaldehyde-treated whole linseed, or no fat source in the concentrate but with 500 g per day of linseed oil being infused into the duodenum. Feed intakes and milk yield were similar among treatments. In general, the lowest digestibility was observed for the formaldehyde-treated whole linseed treatment. Feeding fish oil decreased milk fat and protein percentages. Alpha-linolenic acid increased from 1.0 to 13.9% of milk fatty acids with linseed oil infusion. This confirms the high potential to incorporate alpha-linolenic acid into milk, and suggests that the formaldehyde treatment had little effect to limit biohydrogenation in the rumen. Increasing the supply of alpha-linolenic acid to these cows did not result in an increase in the concentration of eicosapentaenoic acid in milk. Levels of 13,14-dihydro-15-keto-PGF2alpha in plasma were higher for cows receiving formaldehyde-treated linseed and fish oil. Increases in this metabolite in response to oxytocin challenge, tended to be lower for cows given linseed either as sole oil supplement in the diet or as a duodenal infusion of linseed oil. Follicle dynamics were similar among treatments. Larger corpora lutea (CL) were found with cows that received high levels of omega-3 fatty acids through the diet as formaldehyde-treated linseed or as a mixture of formaldehyde-treated linseed and fish oil, although CL were smaller when cows were infused with linseed oil into the duodenum. These results suggest that the improvement in gestation rate that was observed when feeding increased levels of alpha-linolenic acid in earlier work may partly result from lower levels of production of the dienoic prostaglandin PGF2alpha.

Animal Feed↗
PubMed2002

Modulation of sex hormone secretion in cows by acute infection with bovine viral diarrhoea virus.

Bovine viral diarrhoea virus (BVDV) is a major pathogen of cattle and is responsible for considerable reproductive loss. In this study, the in vivo responses in six multiparous cows were investigated after a non-cytopathogenic BVDV challenge (strain Pe 515; 5 x 10(6) tissue culture infective dose 50) given 9 days before a synchronized ovulation. Six similar cows challenged with non-infectious culture medium served as controls. The experimental noncytopathogenic BVDV infection was followed by a viraemia and leucopenia at days 5-9 after challenge, but no other clinical signs of infection were detected. However, the BVDV infection altered endocrine function. Mean LH pulse frequency immediately before CIDR withdrawal was lower (P < or = 0.05) in the BVDV-infected (2.17 +/- 0.34 pulses per 8 h) compared with the sham-infected (4.83 +/- 1.04 pulses per 8 h) animals. At day 3 after CIDR withdrawal, plasma oestradiol concentrations remained high (P < 0.05) in the infected cows (2.19 +/- 0.51 pg ml(-1)) compared with the sham-infected controls (0.72 +/- 0.29 pg ml(-1)). However, there was no difference in the peak oestradiol concentration (BVDV: 2.31 +/- 0.29 versus sham: 2.34 +/- 0.41 pg ml(-1)). In addition, non-cytopathogenic BVDV significantly (P < 0.05) increased the duration of the interval between ovulation and onset of the postovulatory progesterone increase (values 1.0 ng ml(-1)) (BVDV: 3.0 +/- 0.26 versus sham: 4.0 +/- 0.26 days). The viral infection also significantly (P < 0.01) decreased mean plasma progesterone concentrations between day 3 and day 11 after ovulation (BVDV: 2.59 +/- 0.32 versus sham: 4.13 +/- 0.27 ng ml(-1)). These data show that non-cytopathogenic BVDV viraemias during the follicular phase can modulate the secretion of gonadotrophins and sex steroids, in particular progesterone, during a synchronized oestrous cycle. Therefore, viraemias during the follicular phase may reduce the fertility of cattle by disrupting the capacity of the ovulatory follicle to form a competent corpus luteum, thereby compromising early embryo development and maternal recognition of pregnancy.

Acute Disease↗
PubMed2002

Expression of the insulin-like growth factor (IGF) system in the bovine oviduct at oestrus and during early pregnancy.

Early mammalian embryo development in vitro can be enhanced by co-culture with oviductal cells and by the addition of insulin-like growth factors (IGFs). This study examined the expression patterns of the oviductal IGF system in cattle in relation to the number of days after oestrus and the presence or absence of embryos. Oviducts were collected from: (i) 66 nulliparous heifers on day 3, day 6 or day 16 after insemination and from (ii) ten non-pregnant, lactating cows on day 0 or day 1 of the oestrous cycle. Oviducts were coiled, frozen whole and sectioned for in situ hybridization. Expression patterns of mRNAs encoding IGF-I, IGF-II, type 1 IGF receptor (IGF-1R), and the IFG binding proteins (IGFBP)-1, -3 and -5 were determined from autoradiographs. Separate measurements were made for the mucosa and muscle layers of the infundibulum, ampulla and isthmus. None of the parameters measured differed between heifers with or without the presence of an embryo. mRNAs encoding IGF-I and IGF-1R were present in the mucosa and muscle of all three oviductal regions, and the highest value of IGF-I mRNA was measured in heifers on day 3. IGF-II mRNA was expressed predominantly in the muscle wall. IGFBP-1 mRNA was not detectable, whereas mRNAs encoding IGFBP-3 and -5 were expressed in both the muscle and mucosa. IGFBP-3 expression was higher in cows on day 0 and day 1 of the oestrous cycle than in heifers on day 3, day 6 and day 16 after insemination. A peak of IGFBP-5 expression was reached on day 6. Locally or systemically produced IGFs, regulated by IGFBPs, may act directly on the embryo or indirectly via modulation of oviductal secretions and muscular activity to influence the success of early embryo development.

Animals↗
PubMed2002

Production of recombinant ovine interferon tau using a Bombyx mori nuclear polyhedrosis baculovirus expression system.

Ovine interferon tau (oIFN-tau) is an embryonic protein of critical importance in the establishment of pregnancy in the sheep. We have produced recombinant (r) oIFN-tau using a baculovirus expression system and demonstrated the biological activity of the protein produced. Bombyx mori larvae were infected with B. mori nuclear polyhedrosis virus (BmNPV), modified by inserting a cDNA coding for oIFN-tau downstream of the strong polyhedron promoter. Following infection, antiviral activity of the haemolymph rose to a maximum of 3.6 x 10(8) u/mL (equivalent to 3 mg roIFN-tau/mL) by day 5, when haemolymph was collected and stored frozen. Control haemolymph, collected from uninfected insects at an equivalent time, contained no antiviral activity. The roIFN-tau was partially purified by gel filtration column chromatography and the presence of roIFN-tau confirmed by western blotting. The biological activity of the partially purified roIFN-tau was tested in ewes. Treatment with roIFN-tau caused a significant delay in luteolysis confirming biological potency. The results demonstrate that this system can be successfully used to produce large quantities of roIFN-tau.

Animals↗
PubMed2001

Effect of oestradiol treatment during GnRH-induced ovulation on subsequent PGF2alpha release and luteal life span in anoestrous ewes.

In sheep, induction of ovulation during anoestrus is accompanied by a high incidence of short luteal phases, though pre-treatment with progesterone can overcome this problem. We have investigated the effects of supplementing oestradiol during GnRH-induced ovulation on subsequent PGF2alpha release and luteal life span. Thirty anoestrous crossbred ewes received 250 ng GnRH i.v. at 2 h intervals for 48 h to induce ovulation either alone (group 1; n=10) or in association with either an i.m. injection of 20 mg progesterone 3 days earlier (group 2; n=10) or 3 i.m. injections of 10 microg oestradiol at 8 h intervals on the second day of GnRH treatment (group 3; n=10). Laparoscopy, performed 3 days following GnRH to confirm ovulation and 8 days later, coupled with plasma progesterone analysis were used to determine luteal life span. On day 4 following GnRH, plasma samples were collected at 20 min intervals for 8 h to monitor PGF2alpha release. One ewe from group 1 failed to ovulate and was excluded from further analysis. All groups showed an increase (P<0.01) in plasma oestradiol during GnRH treatment, with group 3 showing a marked (P<0.001) increase over that seen in the other two groups. In group 1 there were 1.4+/-0.2 PGF2alpha episodes/ewe/8 h. In group 2, pre-treatment with progesterone caused the complete inhibition of PGF2alpha episodes (0 episodes/ewe/8 h) while in group 3, treatment with oestradiol resulted in a significant reduction (0.3+/-0.1 episodes/ewe/8 h) compared with group 1 (P<0.01). In group 1, 9/9 ewes exhibited short cycles compared with 2/10 ewes in group 2 (P<0.01). In group 3 the proportion of ewes showing short cycles 7/10 ewes was not significantly different from the other groups. While treatment with oestradiol caused a significant attenuation of PGF2alpha release, this was associated with only a partial reduction in the incidence of short cycles.

Anestrus↗
PubMed2001

Modulation of adenosine transport by insulin in human umbilical artery smooth muscle cells from normal or gestational diabetic pregnancies.

1. Adenosine transport was measured in human cultured umbilical artery smooth muscle cells, isolated from non-diabetic or gestational diabetic pregnancies, under basal conditions and after pretreatment in vitro with insulin. 2. Adenosine transport in non-diabetic smooth muscle cells was significantly increased by insulin (half-maximal stimulation at 0.33 +/- 0.02 nM, 8 h) and characterized by a higher maximal rate (V(max)) for nitrobenzylthioinosine (NBMPR)-sensitive (es) saturable nucleoside transport (17 +/- 5 vs. 52 +/- 12 pmol (microg protein)(-1) min(-1), control vs. insulin, respectively) and maximal binding sites (B(max)) for [(3)H]NBMPR (0.66 +/- 0.07 vs. 1.1 +/- 0.1 fmol (microg protein)(-1), control vs. insulin, respectively), with no significant changes in Michaelis-Menten (K(m)) and dissociation (K(d)) constants. 3. In contrast, in smooth muscle cells from diabetic pregnancies, where the values of V(max) for adenosine transport (59 +/- 4 pmol (microg protein)(-1) min(-1)) and B(max) for [(3)H]NBMPR binding (1.62 +/- 0.16 fmol (microg protein)(-1)) were significantly elevated by comparison with non-diabetic cells, insulin treatment (1 nM, 8 h) reduced the V(max) for adenosine transport and B(max) for [(3)H]NBMPR binding to levels detected in non-diabetic cells. 4. In non-diabetic cells, the stimulatory effect of insulin on adenosine transport was mimicked by dibutyryl cGMP (100 nM) and reduced by inhibitors of phosphatidylinositol 3-kinase (10 nM wortmannin), nitric oxide synthase (100 microM N (G)-nitro-L-arginine methyl ester, L-NAME) or protein synthesis (1 microM cycloheximide), whereas inhibition of adenylyl cyclase (100 microM SQ-22536) had no effect. 5. Wortmannin or SQ-22536, but not L-NAME or cycloheximide, attenuated the inhibitory action of insulin on the diabetes-induced stimulation of adenosine transport. 6. Protein levels of inducible NO synthase (iNOS) were similar in non-diabetic and diabetic cells, but were increased by insulin (1 nM, 8 h) only in non-diabetic smooth muscle cells. 7. Our results suggest that adenosine transport via the es nucleoside transporter is modulated differentially by insulin in either cell type. Insulin increased adenosine transport in non-diabetic cells via NO and cGMP, but inhibited the diabetes-elevated adenosine transport via activation of adenylyl cyclase, suggesting that the biological actions of adenosine may be altered under conditions of sustained hyperglycaemia in uncontrolled diabetes.

Adenosine↗
PubMed2001

Validation of an Mx/CAT reporter gene assay for the quantification of bovine type-I interferon.

We describe here a specific and sensitive assay for biologically active bovine type-I interferon (IFN) in an Mx/CAT reporter gene assay. The assay is based on Madin-Darby Bovine Kidney cells transfected with a plasmid, containing a human MxA promoter driving a chloramphenicol acetyltransferase (CAT) cDNA. CAT expression was quantified in a commercially available enzyme linked immunosorbant assay. The response to recombinant bovine INF-alpha(1) was dose dependent between 0.25 and 125.0 iu/ml and was shown to be specific for type-I IFN as no significant effect was seen with a number of other cytokines, including IFN-gamma. This Mx/CAT reporter assay also has advantages in terms of simplicity and reliability over conventional cytopathic effect reduction assays used to quantify the IFN activity in bovine samples. The Mx/CAT reporter assay was used successfully to measure trophoblast derived type-1 IFN activity (IFN-tau) in uterine flushings collected from pregnant cows. IFN-tau is the pregnancy recognition signal produced in ruminants by pre-implantation embryos and was shown to increase markedly between the 12th (0.7+/-0.14 iu/ml) and 18th (44085.0+/-14414.2 iu/ml) day of pregnancy. In contrast, IFN-tau activity remained basal (0.5-0.7 iu/ml) in inseminated non-pregnant animals. Duplicate samples analysed using a cytopathic effect reduction assay correlated well (P<0.001; r(2)=0.945) with IFN levels obtained using the Mx/CAT reporter assay, confirming the reporter assay as a reliable substitute for the standard anti-viral IFN assay.

Animals↗
PubMed2001

Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages.

Amino acid transport in mouse peritoneal macrophages is mediated by several membrane carriers with different substrate specificity and sensitivity to environmental stimuli. We reported previously that transport activities of cystine and arginine in the macrophages were induced markedly by low concentrations of bacterial lipopolysaccharide (LPS). It is known that a variety of macrophage functions are affected by ambient oxygen tension. In this study, we have investigated the effects of oxygen on the induction of amino acid transport activity by LPS and found that the induction of cystine, but not arginine, transport activity was dependent on the ambient oxygen tension. When the macrophages were cultured with 2% O(2) in the presence of 1 ng/ml LPS, induction of cystine transport activity was reduced by approximately 70% compared with cells cultured under normoxic conditions. In macrophages, transport of cystine is mediated by a Na(+)-independent anionic amino acid transporter named system x(c)(-). System x(c)(-) is composed of two protein components, xCT and 4F2hc, and the expression of xCT was closely correlated with system x(c)(-) activity. A putative NF-kappaB binding site was found in the 5'-flanking region of the xCT gene, but the enhanced expression of xCT by LPS and oxygen was not mediated by NF-kappaB binding. An increase in intracellular GSH in macrophages paralleled induction of xCT, but not gamma-glutamylcysteine synthetase. These results suggest the importance of system x(c)(-) in antioxidant defense in macrophages exposed to LPS and oxidative stress.

Amino Acids↗
PubMed2001

Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure.

Patients with chronic renal and heart failure present with hypertension and widespread vasoconstriction, respectively. Although systemic release of nitric oxide (NO) may be elevated in both pathological syndromes, enhanced production of NO fails to overcome endothelial dysfunction. Plasma concentrations of L-arginine, a cationic amino acid precursor for NO synthesis, are reduced whilst levels of the endogenous L-arginine analogues, asymmetric and symmetric dimethyl arginine and N(G)-monomethyl-L-arginine, seem to be elevated. We have reported that transport of L-arginine via the cationic amino acid transporters y(+)/CAT and/or y(+)L are up-regulated in erythrocytes, peripheral blood mononuclear cells and platelets from both patients with either chronic renal or heart failure. A possible explanation why NO serves as a failing counter-regulatory mechanism in both these pathologies is that availability of L-arginine for NO production is reduced despite the observed increase in membrane transport. This review examines the mechanisms underlying alterations in NO production in chronic renal and heart failure, and the possible role of L-arginine transport in vascular and platelet dysfunction observed in both syndromes.

Animals↗
PubMed2001

Hormone control of prostaglandin F(2 alpha) production and oxytocin receptor concentrations in bovine endometrium in explant culture.

The effect of progesterone and estradiol on basal and oxytocin-stimulated prostaglandin F(2 alpha) production and on oxytocin receptor concentrations in endometrium from long term ovariectomized cows was investigated using an explant culture system. Uteri were obtained from cows at slaughter and endometrial explants were cultured in triplicate for up to 96 h in either control media, or media containing progesterone or estradiol. Basal prostaglandin F(2 alpha) production was unaffected by progesterone treatment but was stimulated by estradiol treatment in a dose dependent manner. Oxytocin receptor concentrations remained unchanged in control culture and were unaffected by treatment with estradiol while treatment with progesterone caused a dose-dependent inhibition. Responsiveness to oxytocin, in terms of increased prostaglandin F(2 alpha) production, developed "spontaneously" over the first 24 h of culture and was unaffected by treatment with progesterone or estradiol. In summary the results reveal a dose-dependent inhibition of oxytocin receptor concentration by progesterone and a dose-dependent stimulation of basal PGF(2 alpha) release by estradiol. The reason for the "spontaneous" development of responsiveness to oxytocin remains unknown but may result from the removal of tissue from the influence of an, as yet unidentified, inhibitory factor.

Animals↗
PubMed2001

Hormonal regulation of oxytocin-induced prostaglandin F(2alpha) secretion by the bovine and ovine uterus in vivo.

In long-term ovariectomized ewes and cows, endometrial oxytocin receptors rest at relatively high levels but oxytocin is unable to induce prostaglandin F(2alpha) release. A series of studies were carried out to investigate the roles of physiological levels of progesterone and estradiol in "activating" these receptors in terms of permitting oxytocin-induced prostaglandin F(2alpha) release. In long-term ovariectomized cows, treatment with progesterone, but not estradiol, resulted in the induction of responsiveness to oxytocin. This responsiveness appeared within 2 d of progesterone treatment, reached a maximum by 6 d and was maintained to Day 18. In ovariectomized ewes, while estradiol treatment did induce temporary responsiveness to oxytocin after 3 d of treatment, treatment with progesterone was required to induce sustained responsiveness that appeared by Day 9 of treatment and was maintained to Day 12. Measurement of endometrial receptors for oxytocin revealed a significant decline in oxytocin receptors by Day 6 of progesterone treatment when responsiveness to oxytocin was maximal, demonstrating that receptor concentrations were not a limiting factor. The most likely mechanism by which progesterone treatment induces responsiveness to oxytocin may be through the up regulation of post receptor signaling pathways and/or enzymes involved in prostaglandin synthesis.

Animals↗
PubMed2001

Pregnancy rates during experimentation in dairy cows.

This study investigated pregnancy rates on day 16 in dairy cows following artificial insemination and blood sampling to monitor hormonal status. Collection of blood samples by jugular venepuncture coupled with single fixed time insemination resulted in a poor pregnancy rate (27.8%). Modification of the protocol to include double insemination and collection of blood samples from jugular cannulae inserted four days prior to insemination did not improve pregnancy rate (27.3%). Acclimatization of cows to the experimental facility, however, resulted in a dramatic increase in pregnancy rate (85.7%;P < 0.005). This improvement was not associated with any difference in plasma progesterone but was associated with a marked advancement in the decline in oestradiol at the end of the follicular phase, indicative of earlier ovulation. Non-pregnancy was associated with a delayed fall in oestradiol and reduced plasma concentrations of progesterone. The results support a role for inadequate progesterone in early embryo mortality but suggest that impaired ovulation is a more important problem in cows under the 'stress' of experimentation.

Animals↗
PubMed2001

Vasoactive mediator release by fetal endothelial cells in intrauterine growth restriction and preeclampsia.

OBJECTIVE: Preeclampsia and fetal growth restriction are associated with poor placental perfusion, which may be accompanied by a compensatory release of vasoactive substances in the fetoplacental circuit. This study examines the effects of preeclampsia and fetal growth restriction on nitric oxide and prostacyclin signaling pathways in fetal endothelial cells. STUDY DESIGN: Human umbilical vein endothelial cells from 30 control pregnancies, 18 pregnancies with preeclampsia, and 9 pregnancies with intrauterine growth restriction were cultured. Intracellular cyclic guanosine monophosphate accumulation and 6-keto-prostaglandin F1alpha production were determined. RESULTS: Intracellular accumulation of cyclic guanosine monophosphate was significantly higher in the preeclampsia group and lower in the growth restriction group than in the control group (9.8, 1.8, and 3.9 pmol/microg protein for 5 minutes, respectively), whereas 6-keto-prostaglandin F1alpha production was not significantly different in the 3 groups. CONCLUSION: The data suggest that the fetoplacental vascular response to preeclampsia is to increase production of cyclic guanosine monophosphate, perhaps to maintain vessel dilatation and maximum flow through placental villi. In fetal growth restriction the umbilical vein endothelial cells do not or cannot respond to chronic hypoxia by increasing cyclic guanosine monophosphate, which may lead to fetoplacental vasoconstriction.

6-Ketoprostaglandin F1 alpha↗