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Biomedical subjects

R Webb

Publications and source records attributed to R Webb.

At least 19 recordsLinked to original sources

Enhanced response of granulosa and theca cells from sheep carriers of the FecB mutation in vitro to gonadotropins and bone morphogenic protein-2, -4, and -6.

The FecB (Booroola) mutation, which leads to increased ovulation rates and multiple births in sheep, is now known to occur in the signaling domain of the bone morphogenic protein (BMP)-1B receptor. We examined the effect of the mutation on the responsiveness of granulosa (GC) and theca cells (TC) to BMPs and other local regulators using tissue from animals with (Fec(B/B)) and without (Fec(+/+)) the FecB mutation. Experiments examined the effect of BMP-2, -4, and -6 (0.005-50 ng/ml), and their interaction with IGF-I (0.1-10 ng/ml LR3 analog) and gonadotropins, on the proliferation and differentiation of GCs and TCs isolated from small (<2 mm) antral follicles and maintained in serum-free culture for up to 8 d. Dose-finding studies using ovaries from wild-type sheep obtained from the abbattoir showed no difference among the different BMPs in stimulating (P < 0.001) estradiol (E2) production by GCs cultured with FSH (10 ng/ml), but there was a clear interaction (P < 0.001) with IGF-I. BMPs had no effect on GC proliferation or the sensitivity of GCs to FSH. In contrast, higher doses of BMPs (5-50 ng/ml) inhibited LH-stimulated androstenedione production by TCs, whereas lower doses (0.005-0.05 ng/ml) stimulated TC proliferation (P < 0.01). Regardless of dose of IGF-I, at the end of culture (96-192 h) hormone production by GCs (E2, inhibin A) and TCs (androstenedione) was 4- to 5-fold greater (P < 0.001) by cells from Fec(B/B), compared with Fec(+/+) ewes exposed to the same dose of gonadotropin. In the presence of low concentrations of IGF-I (0.1 ng/ml), the maximum increase in the production of E2 and inhibin A by GCs from FF ewes in response to BMPs was observed at doses that were 3- to 10-fold lower (3-10 ng/ml) than ++ (30 ng/ml; P < 0.001). Low doses of BMPs stimulated proliferation of TCs from ++ (P < 0.01) but not FF ewes. Immunohistochemistry confirmed BMP-6 protein expression in the oocyte, granulosa, and thecal layers of antral follicles from both genotypes. These results confirm a major role for BMPs in controlling ovarian somatic cell function in sheep and provide evidence to support the hypothesis that the FecB mutation increases the BMP response of somatic cells when stimulated to differentiate by gonadotropins.

Animals↗

Key worker services for disabled children: what characteristics of services lead to better outcomes for children and families?

BACKGROUND: Research has shown that families of disabled children who have a key worker benefit from this service and recent policy initiatives emphasize the importance of such services. However, research is lacking on which characteristics of key worker schemes for disabled children are related to better outcomes for families. METHODS: A postal questionnaire was completed by 189 parents with disabled children who were receiving a service in seven key worker schemes in England and Wales. Path analysis was used to investigate associations between characteristics of the services and outcomes for families (satisfaction with the service, impact of key worker on quality of life, parent unmet need, child unmet need). RESULTS: The four path models showed that key workers carrying out more aspects of the key worker role, appropriate amounts of contact with key workers, regular training, supervision and peer support for key workers, and having a dedicated service manager and a clear job description for key workers were associated with better outcomes for families. Characteristics of services had only a small impact on child unmet need, suggesting that other aspects of services were affecting child unmet need. CONCLUSIONS: Implications for policy and practice are discussed, including the need for regular training, supervision and peer support for key workers and negotiated time and resources for them to carry out the role. These influence the extent to which key workers carry out all aspects of the key worker's role and their amount of contact with families, which in turn impact on outcomes.

Adolescent↗

Body composition, dietary carbohydrates and fatty acids determine post-fertilisation development of bovine oocytes in vitro.

This study assessed the interactive effects of carbohydrate type (fibre vs starch) and fatty acid (FA) supplementation (0% vs 6% calcium soaps of palm oil FA) on the post-fertilisation development of oocytes recovered from low and moderate body condition score (BCS) heifers. A secondary objective was to compare the FA composition of plasma to that of granulosa cells (GCs) and cumulus-oocyte complexes (COCs) from these animals, and to relate these findings to the developmental potential of oocytes. Plasma, GCs and COCs were recovered from 32 heifers on day 5 of a synchronised oestrous cycle for FA analyses. Oocytes were also recovered on days 10 and 15 of the same cycle after short-term ovarian stimulation (FSH + GnRH), and matured, fertilised and cultured to the blastocyst stage in vitro. High levels of dietary starch increased (P < 0.01) plasma insulin but, together with dietary FA, reduced (P < 0.05) blastocyst yields in low, but not in moderate, BCS heifers. Diet-induced alterations to the FA content of plasma were less apparent in GCs and COCs. In summary, although dietary lipids increased the FA content of COCs, the selective uptake of saturated FAs at the expense of mainly polyunsaturated FAs within the follicular compartment ensured that the FA composition of COCs was largely unaffected by diet. However, the concentration of saturated FAs within COCs was inherently high, and so further increases in FA content may have impaired post-fertilisation development. The data establish a robust nutritional framework for more detailed studies into the mechanistic effects of dietary composition on the post-fertilisation developmental potential of oocytes.

Animal Feed↗

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling.

OBJECTIVES: To assess the relative effectiveness, patient acceptability, costs and cost-effectiveness of four strategies for the prevention of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal (GI) toxicity: (1) Cox-1 NSAIDs plus histamine-2 receptor antagonist (H2RA), (2) Cox-1 NSAIDs plus proton pump inhibitors (PPIs), (3) Cox-1 NSAIDs plus misoprostol, and (4) Cox-2 NSAIDs (later expanded to 4a Cox-2 coxibNSAIDs and 4b Cox-2 preferential NSAIDs). DATA SOURCES: Electronic databases up to May 2002. REVIEW METHODS: Relevant studies were selected, assessed and analysed. Pooled relative risk ratios (RR) from the systematic review were combined with up-to-date UK resource use and unit costs data in an incremental economic analysis. A probabilistic decision-analytic model was designed and populated with data to carry out incremental economic analysis. Incremental cost-effectiveness ratios (ICERs) were generated for the outcome measure, endoscopic ulcer or serious GI event averted, against total cost, and non-parametric bootstrapping was used to simulate variance of these ICERs. RESULTS: Of 118 selected trials, including 125 relevant comparisons (which included 76,322 participants) only 138 deaths and 248 serious GI events were reported. Seven comparisons were judged to be at low risk of bias. Comparing the gastroprotective strategies against placebo, there was no evidence of effectiveness of H2RAs against any primary outcomes (few events reported), PPIs may reduce the risk of symptomatic ulcers [RR 0.09, 95% confidence interval (CI) 0.02 to 0.47], misoprostol reduces the risk of serious GI complications (RR 0.57, 95% CI 0.36 to 0.91) and symptomatic ulcers (RR 0.36, 95% CI 0.20 to 0.67), Cox-2 'preferentials' reduce the risk of symptomatic ulcers (RR 0.41, 95% CI 0.26 to 0.65) and Cox-2 'coxibs' reduce the risk of symptomatic ulcers (RR 0.49, 95% CI 0.38 to 0.62) and possibly serious GI events (RR 0.55, 95% CI 0.38 to 0.80). All strategies except Cox-2 'preferentials' reduce the risk of endoscopic ulcers. There were only 12 direct comparisons between gastroprotective strategies. All they suggest is that Cox-2 preferentials are better than misoprostol for preventing GI complications. Indirect comparisons suggested that PPIs may prevent symptomatic ulcers better than Cox-2 coxibs, but this is very weak evidence. For prevention of endoscopic ulcers PPIs and misoprostol appear more successful than H2RAs and misoprostol is better than Cox-2 preferentials. There were no UK head-to-head published economic analyses with regard to the main gastroprotective strategies. There were generally insufficient data with regards to cardiac or renal outcomes, serious GI outcomes or life-years gained to populate the mode. Mean (2.5th and 97.5th percentile) costs per endoscopic ulcer averted compared with Cox-1 NSAIDs alone were as follows: Cox-1 plus H2RAs, -186 pounds (-555 to 804); Cox-1 plus PPIs, 454 pounds (251 to 877); Cox-1 plus misoprostol, 54 pounds (-112 to 238); Cox-2 selective NSAIDs, 263 pounds (-570 to 1280), or Cox-2 specific NSAIDs, 301 pounds (189 to 418). With regard to the prevention of endoscopic ulcers, Cox-1 NSAID plus H2RA is a dominant option. Cost-effectiveness acceptability analysis showed a 95% probability that this combination was less costly and more effective. Cost-effectiveness acceptability frontiers showed that if the decision-maker is willing to pay up to 750 pounds to avoid an endoscopic ulcer, then Cox-1 plus H2RA is the optimal strategy. If the decision-maker is willing to pay over 750 pounds, the optimal strategy is NSAID plus misoprostol. Between 1900 pounds and 3750 pounds, Cox-2 selective inhibitors are optimal, and over 3750 pounds, Cox-2 specific inhibitors become optimal. NSAID plus PPI is never the optimal strategy. Sensitivity and subgroup analyses suggest that Cox-1 NSAID plus H2RA and Cox-1 NSAID plus misoprostol become more cost-effective in the older age group. Some conclusions were associated with high levels of uncertainty. CONCLUSIONS: Although there is a very large body of evidence comparing Cox-2 NSAIDs with Cox-1 NSAIDs, this is not matched by studies of the other types of gastroprotectors or by studies directly comparing active gastroprotective strategies. This lack of direct comparisons led to the use of indirect comparisons to help understand the relative efficacy of these strategies. Indirect evidence in itself is weak and was also hampered by lack of evidence in the underlying studies (where the gastroprotectors were compared with placebo). Economic modelling suggests that Cox-1 NSAID plus H2RA or Cox-1 NSAID plus PPI are the most cost-effective strategies for avoiding endoscopic ulcers in patients requiring long-term NSAID therapy. All strategies other than Cox-2 selective inhibitors reduce the rate of endoscopic ulcer compared with Cox-1 alone. The economic analysis suggests that there may be a case for prescribing H2RAs in all patients requiring NSAIDs. Misoprostol is more effective, but is associated with a greater cost and GI side-effects which may be unacceptable for patients. However, when assessing serious GI events, the economic analysis is sufficiently weakened by the data available as to render clear practice recommendations impossible. Further large, independent RCTs directly comparing various gastroprotective strategies are needed. These should report items such as major outcomes, primary data, adverse events, assessment of practice and patient preference.

Anti-Inflammatory Agents, Non-Steroidal↗

Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development.

In the neonate, adipose tissue and the lung both undergo a rapid transition after birth, which results in dramatic changes in uncoupling protein abundance and glucocorticoid action. Leptin potentially mediates some of these adaptations and is known to promote the loss of uncoupling protein (UCP)1, but its effects on other mitochondrial proteins or glucocorticoid action are not known. We therefore determined the effects of acute and chronic administration of ovine recombinant leptin on brown adipose tissue (BAT) and/or lung in neonatal sheep. For the acute study, eight pairs of 1-day-old lambs received, sequentially, 10, 100, and 100 mug of leptin or vehicle before tissue sampling 4 h from the start of the study, whereas in the chronic study, nine pairs of 1-day-old lambs received 100 mug of leptin or vehicle daily for 6 days before tissue sampling on day 7. Acute leptin decreased the abundance of UCP2, glucocorticoid receptor, and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 mRNA and increased 11beta-HSD type 2 mRNA abundance in BAT, a pattern that was reversed with chronic leptin administration, which also diminished lung UCP2 protein abundance. In BAT, UCP2 mRNA abundance was positively correlated to plasma leptin and nonesterified fatty acids and negatively correlated to mean colonic temperature in the leptin group at 7 days. In conclusion, leptin administration to the neonatal lambs causes differential effects on UCP2 abundance in BAT and lung. These effects may be important in the development of these tissues, thereby optimizing lung function and fat growth.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

Impact of nutrition on oocyte quality: cumulative effects of body composition and diet leading to hyperinsulinemia in cattle.

The present study sought to assess the combined effects of body composition and diet (level of feeding) on the postfertilization developmental potential of oocytes recovered from heifers using ultrasound-guided transvaginal follicular aspiration and to relate oocyte quality to the metabolic status of these animals. By collecting oocytes on repeated occasions spanning several weeks, it was possible to assess the cumulative effects of changes in nutritional status on oocyte quality over this period. Twenty-four heifers of low and moderate body condition were placed on one of two levels of feeding (equivalent to once or twice the maintenance requirements of these animals). Oocytes were recovered at two defined time points within each of three successive estrous cycles and were matured, fertilized, and cultured to the blastocyst stage in vitro. The results show that the effect of feeding level on oocyte quality is dependent on the body condition of the animal, with the high level of feeding being beneficial to oocytes from animals of low body condition but detrimental to oocytes from animals of moderately high body condition. Furthermore, the effects of high levels of feeding on oocyte quality were cumulative, with blastocyst yields for relatively fat heifers on twice the maintenance requirement deteriorating with time relative to yields for relatively thin heifers on the same level of feeding. Finally, a significant proportion of the moderately fat animals on the high level of feeding were hyperinsulinemic, and we show, to our knowledge for the first time in ruminants, that this condition is associated with impaired oocyte quality.

Animal Nutritional Physiological Phenomena↗

Interaction potentials of the RG-I anions, neutrals, and cations (RG = He, Ne, Ar).

Interaction potentials of the iodine atom, atomic cation, and anion with light rare-gas atoms from He to Ar are calculated within the unified ab initio approach using the unrestricted coupled-cluster with singles and doubles and perturbative treatment of triples correlation treatment, relativistic small-core pseudopotential, and an extended basis set. Ab initio points are fit to a flexible analytical function. The calculated potentials are compared with available literature data, assessed in the I(-)-and I+-ion mobility calculations and the Ar-I(-)-anion zero electron kinetic-energy spectra simulations, and analyzed using the correlation rules. The results indicate a high precision of the reported potentials.

Journal Article↗

Metabolic variables and plasma leptin concentrations in dairy cows exhibiting reproductive cycle abnormalities identified through milk progesterone monitoring during the post partum period.

We have used milk progesterone analysis to monitor reproductive function in lactating dairy cows and have then related this reproductive function to a variety of metabolic variables. Monitoring of cows (n = 41) during the period of onset of luteal function (first milk progesterone reading>5 ng/ml) revealed that delayed onset was associated with increased milk yield and greater loss of body weight and body condition but was not related to plasma metabolite or leptin concentrations. Further monitoring of reproductive function in these 41 cows and an additional 33 cows (total n = 74) during the mating period (from weeks 6 to 14 post partum) identified reproductive cycle abnormalities in 29 (39.2% of animals). The occurrence of cycle abnormalities was associated with increased milk yield (P < 0.05), elevated plasma beta hydroxybutyrate (P < 0.05) and reduced plasma leptin (P < 0.01) concentrations as well as a lower (P < 0.05) rate of gain of body weight and condition score but was not associated with plasma urea or glucose concentrations. Furthermore, cows exhibiting cycle abnormalities had a longer (P < 0.01) interval to first service and a smaller percentage had conceived by 100 days post partum (34.5% versus 66.7%; P < 0.01). These results provide further evidence that impaired reproductive function during the post partum period in dairy cows is caused by a poor energy status and not elevated urea concentrations. Reduced plasma leptin concentrations in animals suffering reproductive dysfunction further supports this view.

3-Hydroxybutyric Acid↗

Differential staining combined with TUNEL labelling to detect apoptosis in preimplantation bovine embryos.

Development of accurate laboratory methods to assess embryo quality will improve the efficiency of embryo production from in-vitro culture systems. Currently, the techniques of TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end (TUNEL) labelling for the detection of apoptosis, and differential staining for determining the ratio of inner cell mass (ICM) to trophectoderm (TE) cells, are used separately to assess embryo quality in a range of different species. This paper reports a unique, simple and fast method for the assessment of embryo quality using differential staining of TE and ICM, but combined with TUNEL labelling (DST staining). This technique was used to investigate the effect of serum supplementation on total cell number, ICM:TE ratio and apoptosis index after in-vitro production of bovine embryos. Serum supplementation increased total cell number (P < 0.01), but reduced the ratio of ICM:TE cells. No differences were observed in the number of apoptotic nuclei between treatments, or in the localization of the apoptotic nuclei. However, more apoptotic nuclei were observed in ICM than TE cells in both culture groups. In conclusion, using DST, it has been possible to carry out both a qualitative and quantitative analysis of embryos produced using the two different methods. DST provides a means of assessing the effect of culture conditions on cell number of both embryo compartments (ICM and TE), as well as providing information on the localization of apoptotic nuclei within the blastocyst.

Animals↗

Production of matrix metalloproteinases by cultured bovine theca and granulosa cells.

Matrix metalloproteinases (MMPs) degrade the proteinaceous components of the extracellular matrix and are presumably essential for follicular growth culminating in ovulation or atresia. The objectives of this study were to characterize the gelatinolytic and caseinolytic MMPs secreted by cultured bovine thecal and granulosal cells and to determine the effect of luteinizing hormone (LH) on MMP secretion. Thecal and granulosal cells were collected from small bovine follicles (<5 mm) on day 2 or 5 of the estrous cycle (day 0=estrus). A serum-free culture system was utilized in which bovine thecal and granulosal cells do not spontaneously luteinize, but produce androstenedione and estradiol in response to physiological concentrations of LH and follicle-stimulating hormone (FSH) respectively. The effect of LH (0, 1 or 100 ng/ml) on MMP production was determined in conditioned media collected every 48 h for 144 h. MMPs were detected by gelatin and casein zymography and MMP activity was quantified by image analysis. Thecal and granulosal cell conditioned media contained MMPs that had a relative molecular size (Mr) ranging from 53,000 to 200,000 and addition of 1,10 phenanthroline (MMP inhibitor) blocked gelatinolytic and caseinolytic activity. Patterns of gelatinolytic activity in thecal and granulosal cell conditioned media differed over time with the Mr 62,000 and 83,000 MMPs being increased (P <0.05) and the Mr 53,000 MMP being decreased (P <0.05) at 96 h of culture. LH (1 or 100 ng/ml) increased (P <0.05) gelatinolytic activity of the Mr 53,000 and 62,000 gelatinases within thecal cell conditioned media but not granulosal cell conditioned media. The Mr 62,000 and 83,000 gelatinolytic activities corresponded to the active forms of gelatinase A (Mr 62,000) and B (Mr, 83,000) and gelatinase A was detected in thecal cell conditioned media by Western blot analysis. Caseinolytic activity (Mr 83,000) was detected in both thecal and granulosal cell conditioned media and increased from 48 to 96 h. In summary, thecal and granulosal cells secrete gelatinolytic and caseinolytic MMPs and thecal cell production of gelatinase A was stimulated by LH.

Animals↗

Prolactin, the prolactin receptor and uncoupling protein abundance and function in adipose tissue during development in young sheep.

A primary role of the prolactin receptor (PRLR) during fetal and postnatal development has been suggested to be the regulation of uncoupling protein (UCP) expression. We, therefore, determined whether: (1) the rate of loss of UCP1 from brown adipose tissue after birth was paralleled by the disappearance of PRLR; and (2) administration of either pituitary extract prolactin (PRL) containing a mixture of posttranslationally modified forms or its pseudophosphorylated form (S179D PRL) improved thermoregulation and UCP1 function over the first week of neonatal life. PRLR abundance was greatest in adipose tissue 6 h after birth before declining up to 30 days of age, a trend mirrored by first a gain and then a loss of UCP1. In contrast, in the liver--which does not possess UCPs--a postnatal decline in PRLR was not observed. Administration of PRL resulted in an acute increase in colonic temperature in conjunction with increased plasma concentrations of non-esterified fatty acids and, as a result, the normal postnatal decline in body temperature was delayed. S179D PRL at lower concentrations resulted in a transient rise in colonic temperature at both 2 and 6 days of age. In conclusion, we have demonstrated a close relationship between the ontogeny of UCP1 and the PRLR. Exogenous PRL administration elicits a thermogenic effect suggesting an important role for the PRLR in regulating UCP1 function.

Adipose Tissue↗

Tissue-specific effects of leptin administration on the abundance of mitochondrial proteins during neonatal development.

Many tissues undergo a rapid transition after birth, accompanied by dramatic changes in mitochondrial protein function. In particular, uncoupling protein (UCP) abundance increases at birth in the lung and adipose tissue, to then gradually decline, an adaptation that is important in enabling normal tissue function. Leptin potentially mediates some of these changes and is known to promote the loss of UCP1 from brown fat but its effects on UCP2 and related mitochondrial proteins (i.e. voltage-dependent anion channel (VDAC) and cytochrome c) in other tissues are unknown. We therefore determined the effects of once-daily jugular venous administration of ovine recombinant leptin on mitochondrial protein abundance as determined by immunoblotting in tissues that do (i.e. the brain and pancreas) and do not (i.e. liver and skeletal muscle) express UCP2. Eight pairs of 1-day-old lambs received either 100 mug leptin or vehicle daily for 6 days, before tissue sampling on day 7. Administration of leptin diminished UCP2 abundance in the pancreas, but not the brain. Leptin administration had no affect on the abundance of VDAC or cytochrome c in any tissue examined. In leptin-administered animals, but not controls, UCP2 abundance in the pancreas was positively correlated with VDAC and cytochrome c content, and UCP2 abundance in the brain with colonic temperature. In conclusion, leptin administration to neonatal lambs causes a tissue-specific loss of UCP2 from the pancreas. These effects may be important in the regulation of neonatal tissue development and potentially for optimising metabolic control mechanisms in later life.

Animals↗

Relationship between low-molecular-weight insulin-like growth factor-binding proteins, caspase-3 activity, and oocyte quality.

Bovine follicular atresia is associated with the apoptosis of granulosa cells and the subsequent loss of oocyte competence through the reduction of cellular contact (e.g., gap junctions). Several components of the insulin-like growth factor (IGF) system are thought to affect follicular atresia. Whereas the IGF-binding proteins (IGFBPs) are present in varying quantities throughout follicular development, IGFBP-5 appears to be present only during atresia, in parallel with its regulation in other tissue remodeling systems. However, to our knowledge, no connection has yet been made between atresia, low-molecular-weight IGFBP content, and oocyte quality in the bovine ovary. Caspases are actively involved in ovarian follicular atresia, and apoptosis in antral follicles is caspase-3-dependent. Hence, the aim of the present study was to investigate the use of these factors in the assessment of oocyte quality and developmental potential. Oocytes were aspirated, morphologically classified, and individually matured in vitro. The follicular fluid and granulosa cells of these follicles were analyzed for IGFBP profile and caspase-3 activity, respectively. A significant correlation was found between the presence of low-molecular-weight IGFBPs in bovine follicular fluid and caspase-3 activity of granulosa cells isolated from individual follicles. The highest percentage of development to the blastocyst stage was observed in oocytes from slightly atretic follicles. This group of oocytes contained an equal proportion of oocytes at grades 1-3. These data demonstrate that low-molecular-weight IGFBP profile is a more reliable method than the traditional morphological assessment of oocytes and can be used as an effective marker of developmentally competent oocytes. Importantly, these results have implications for the use of noninvasive follicular fluid markers in the selection of competent oocytes to improve outcomes of in vitro fertilization.

Animals↗

A national audit of joint mother and baby admissions to UK psychiatric hospitals: an overview of findings.

The Marcé Clinical Audit is an ongoing data collection exercise that gathers socio-demographic and clinical information about mothers and their infants, admitted jointly to specialist units in UK psychiatric hospitals. The maternal and parenting outcomes, in particular of mothers with schizophrenia and mothers who harm themselves and/or their infants, were determined and analysed. The majority of women had a primary diagnosis of either depression (43%) or schizophrenia (21%). Mothers with schizophrenia were three times more likely to experience a poor outcome than non-schizophrenic mothers, were more likely to be separated from their infant at discharge and were perceived, by staff, to be at greater risk of harming their infant. They were, however, shown to be no more likely to cause actual harm to their infant, or themselves, than non-schizophrenic mothers.

Adolescent↗

Endocrine and paracrine control of follicular development and ovulation rate in farm species.

Productivity in farm species is controlled by many factors, including ovulation rate. In cattle, single ovulations occur most frequently and in sheep (and goats) the number of ova released can range from one to many depending upon the breed, whilst the pig is polyovular. The processes of recruitment and selection determine the number of ovulatory follicles in all these species with FSH and subsequently LH playing major roles. GnRH-agonist models in which endogenous gonadotrophin secretion is suppressed and exogenous LH and/or FSH are administered at specific concentrations in defined patterns, are useful in all three species for elucidating the precise roles of specific hormones in stimulating follicular development. Differences in the hypothalamic-pituitary-ovarian feedback response lead to the differences in the number of ovulatory follicles, as does the pool of antral follicles from which the ovulatory ones are selected. Precocious development of follicles is also associated with more ovulations, as is the case with the Booroola due to the single gene acting through bone morphogenetic proteins (BMPs). It is well established that ovulation rate can also be influenced by exogenous hormone administration and by environmental factors such as nutrition. It has become apparent that these nuritional effects are mediated by a direct action at the level of the ovary, involving insulin, insulin-like growth factors (IGF) I and II and their binding proteins among other factors. These factors can also affect the quality of the oocyte and consequently embryo development and survival. Recently, the regulation of follicular angiogenesis has been shown to be important for the development of ovulatory follicles, particularly vascular endothelial growth factor (VEGF) which is produced primarily by the granulosa cells within the ovary and can be stimulated by gonadotrophins. Administration of VEGF has been shown to stimulate pre-antral follicular growth and increase the number of pre-ovulatory follicles. In summary both extra- and intra-ovarian factors are involved in the control of ovulation rate. Manipulation of the angiogenic process may also provide new opportunities for regulating the quality and number of follicles that ovulate.

Animal Nutritional Physiological Phenomena↗

Resumption of follicle growth in gilts after ovarian autografting.

The aims of the study were to evaluate autografting of porcine ovarian tissue in terms of establishment of a blood supply, follicle survival and development, commencement of oestrous cycles and endocrine patterns in this polyovular species. Experiment 1, a preliminary study on four gilts, showed that ovarian tissue slices survived the grafting procedure and re-vascularised. In Experiment 2, a further six pre-pubertal gilts had both ovaries surgically removed and two thin cortical slices of each ovary were immediately reattached to each of the ovarian pedicles. Blood samples were taken at surgery and then weekly. Two gilts were slaughtered 2 weeks after surgery and ovarian tissue recovered. The remaining four gilts underwent daily checks for behavioural oestrus until slaughter 24 weeks after surgery. All four gilts showed standing heat at least once prior to slaughter. Plasma LH and FSH concentrations increased significantly (P<0.01) by 3 days after surgery, then fell gradually, but did not return to pre-surgery levels. Progesterone concentrations showed some evidence of cyclicity in all animals. In the grafted tissue, re-vascularisation of the tissue was apparent by 2 weeks post-grafting, although no preantral or antral follicles were observed. The tissue recovered after 24 weeks contained healthy preantral and antral follicles, luteal tissue and some large cystic follicles. It is unclear whether these cysts were the result of ovarian or hypothalamic/pituitary disturbance. In conclusion, the results of this study have shown that follicle growth and resumption of cyclicity can be achieved following ovarian autografting in pigs and indicate that this will be a useful model for investigating the mechanisms that control the early stages of follicular growth and ultimately ovulation rate in this multiovular species.

Animals↗

Uptake for cervical screening by ethnicity and place-of-birth: a population-based cross-sectional study.

Previous research indicates low screening uptake among South Asian women. We aimed to generate contemporary evidence of uptake by ethnicity using the screening records of eligible women resident in Manchester (n = 72613). Uptake among South Asians was lower than among other women, a difference explained by area- and practice-level confounding. A higher proportion of South Asians were recorded as 'never screened', an effect only partially explained by confounding. In practices with relatively large South Asian populations, uptake was higher among South Asians. Women born in a diverse range of overseas countries had uptake rates below 60 per cent and approximately a third of women born overseas were recorded as 'never screened'. If comprehensive coverage is to be achieved in inner city areas attention should now focus on the needs of a diverse range of ethnic minority groups other than South Asians. The routine collection of ethnicity data in primary care is also indicated.

Adult↗