Understanding the trade-off between the environment and fertility in cows and ewes.

The environment contributes to production diseases that in turn badly affect cow performance, fertility and culling. Oestrus intensity is lower in lame cows, and in all cows 26% potential oestrus events are not expressed (to avoid getting pregnant). To understand these trade-offs, we need to know how animals react to their environment and how the environment influences hypothalamus-pituitary-adrenal axis (HPA) interactions with the hypothalamus-pituitary-ovarian axis (HPO).

Immunolocalization of c-Fos, ELOVL5 and oestradiol in the ewe vulva in relation to oestrus behaviour after treatment with lipopolysaccharide.

Sudden activation of the stress axis by a lipopolysaccharide endotoxin (LPS) significantly reduces ewes' sexual attractivity to rams by delaying all signs of oestrous behaviour. To understand mechanisms involved in attracting male interest, we examined c-Fos (nuclear activation), ELOVL5 (enzyme involved in pheromone synthesis) and oestradiol receptors (ER) using immunohistochemistry on ewe vulval tissue at 0, 31 and 40 hr in the ovarian follicular phase with or without exposure to LPS at 28 hr (5 groups of 4 ewes per group). While there was intense staining for immunoreactive (IR)-c-Fos and IR-ELOVL5 in the vulval epithelium and sebaceous glands, there were no differences in intensity between groups of ewes.

Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

Background: Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer.

Aim: To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™.

Does Reader Performance with Digital Breast Tomosynthesis Vary according to Experience with Two-dimensional Mammography?

Purpose To assess whether individual reader performance with digital breast tomosynthesis (DBT) and two-dimensional (2D) mammography varies with number of years of experience or volume of 2D mammograms read. Materials and Methods After written informed consent was obtained, 8869 women (age range, 29-85 years; mean age, 56 years) were recruited into the TOMMY trial (A Comparison of Tomosynthesis with Digital Mammography in the UK National Health Service Breast Screening Program), an ethically approved, multicenter, multireader, retrospective reading study, between July 2011 and March 2013. Each case was read prospectively for clinical assessment and to establish ground truth.

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial).

Purpose: To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features.

Materials And Methods: In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29-85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images.

The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme--a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone.

Background: Digital breast tomosynthesis (DBT) is a three-dimensional mammography technique with the potential to improve accuracy by improving differentiation between malignant and non-malignant lesions.

Objectives: The objectives of the study were to compare the diagnostic accuracy of DBT in conjunction with two-dimensional (2D) mammography or synthetic 2D mammography, against standard 2D mammography and to determine if DBT improves the accuracy of detection of different types of lesions.

Study Population: Women (aged 47-73 years) recalled for further assessment after routine breast screening and women (aged 40-49 years) with moderate/high of risk of developing breast cancer attending annual mammography screening were recruited after giving written informed consent.

Breast cancer risk reduction--is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

Background: Breast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness.

Activation of cells containing estrogen receptor alpha or somatostatin in the medial preoptic area, arcuate nucleus, and ventromedial nucleus of intact ewes during the follicular phase, and alteration after lipopolysaccharide.

Cells in the medial preoptic area (mPOA), arcuate nucleus (ARC), and ventromedial nucleus (VMN) that possess estrogen receptor alpha (ER alpha) mediate estradiol feedback to regulate endocrine and behavioral events during the estrous cycle. A percentage of ER alpha cells located in the ARC and VMN express somatostatin (SST) and are activated in response to estradiol. The aims of the present study were to investigate the location of c-Fos, a marker for activation, in cells containing ER alpha or SST at various times during the follicular phase and to determine whether lipopolysaccharide (LPS) administration, which leads to disruption of the luteinizing hormone (LH) surge, is accompanied by altered ER alpha and/or SST activation patterns.

Innate immunity and inflammation of the bovine female reproductive tract in health and disease.

Mammalian reproductive physiology and the development of viviparity co-evolved with inflammation and immunity over millennia. Many inflammatory mediators contribute to paracrine and endocrine signalling, and the maintenance of tissue homeostasis in the female reproductive tract. However, inflammation is also a feature of microbial infections of the reproductive tract.

Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

Background: The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual.

Methods: Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL).

The effect of Escherichia coli lipopolysaccharide and tumour necrosis factor alpha on ovarian function.

Problem: Pelvic inflammatory disease and metritis are important causes of infertility in humans and domestic animals. Uterine infection with Escherichia coli in cattle is associated with reduced ovarian follicle growth and decreased estradiol secretion. We hypothesized that this effect could be mediated by the bacterial lipopolysaccharide (LPS) or cytokines such as tumour necrosis factor alpha (TNFalpha).

Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2alpha to prostaglandin E2 in bovine endometrium.

Escherichia coli infection of the endometrium causes uterine disease after parturition and is associated with prolonged luteal phases of the ovarian cycle in cattle. Termination of the luteal phase is initiated by prostaglandin F(2alpha) (PGF) from oxytocin-stimulated endometrial epithelial cells. Compared with normal animals, the peripheral plasma of animals with E.

Ovarian follicular cells have innate immune capabilities that modulate their endocrine function.

Oestrogens are pivotal in ovarian follicular growth, development and function, with fundamental roles in steroidogenesis, nurturing the oocyte and ovulation. Infections with bacteria such as Escherichia coli cause infertility in mammals at least in part by perturbing ovarian follicle function, characterised by suppression of oestradiol production. Ovarian follicle granulosa cells produce oestradiol by aromatisation of androstenedione from the theca cells, under the regulation of gonadotrophins such as FSH.

Stress, behaviour and reproductive performance in female cattle and pigs.

Female farm animals are exposed to a great variety of environmental and management related stressors. As a consequence, their reproductive and maternal abilities may be compromised through mechanisms acting on the hypothalamic, pituitary, ovarian and uterine function. Responses to short- and long-term stressors may differ as short-term stressors often fail to affect reproduction or even may have stimulatory effects.

The management of bovine reproduction in elite herds.

The management of bovine reproduction is the cornerstone of health provision in elite herds. Aims and objectives for reproductive performance should be herd specific and data to monitor progress should not only be frequently collected, but also analysed and reported. Strategic monitoring of animals should include a vaginal examination for evidence of uterine disease, as well as transrectal ultrasonography of the genital tract.

Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus.

Prostaglandins have a central role in many endocrine functions in mammals, including regulation of the life span of the corpus luteum by prostaglandin F(2alpha) (PGF) and prostaglandin E2 (PGE), which are secreted by the uterine endometrium. However, the uterus is readily infected with bacteria such as Escherichia coli, which disrupt luteolysis. Immune cells detect E.

Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle.

Bacteria contaminate the uterus of most dairy cattle after parturition and endometritis causes infertility. An endometritis score can be ascribed based on the vaginal mucus character and odour but it is not clear if the clinical score reflects the number of uterine bacteria or the inflammatory response. The present study tested the hypothesis that clinical evaluation of endometritis reflects the number of bacteria present in the uterus, and the acute phase protein response.

A conceptual model of the influence of stress on female reproduction.

Intriguingly, similar neurotransmitters and nuclei within the hypothalamus control stress and reproduction. GnRH neurone recruitment and activity is regulated by a balance between stimulation, suppression and permissiveness controlled by noradrenaline, neuropeptide Y and serotonin from the brain stem, impact from glutamate in the medial preoptic area and neuropeptide Y in the arcuate nucleus, in opposition to the restraining influences of gamma-aminobenzoic acid within the medial preoptic area and opioids from the arcuate nucleus. Stress also activates neuropeptide Y perikarya in the arcuate nucleus and brain stem noradrenaline neurones.

The effect of intrauterine administration of estradiol on postpartum uterine involution in cattle.

In cattle, the first postpartum dominant follicle has a predilection for the ovary contralateral to the previously gravid uterine horn. However, the presence of an estradiol-secreting dominant follicle in the ipsilateral ovary is a marker of subsequent fertility, possibly due to a localized effect of ovarian estradiol on uterine involution. The present study tested the hypothesis that estradiol increases the rate of uterine involution when administered into the previously gravid uterine horn around the expected time of selection of the first postpartum dominant follicle.

Effect of the regressing corpus luteum of pregnancy on ovarian folliculogenesis after parturition in cattle.

In cattle, the first postpartum dominant follicle has a predilection for the ovary contralateral to the previously gravid uterine horn, possibly due to a local inhibitory effect of the regressing corpus luteum of pregnancy in the ipsilateral ovary. The aim of the present study was to test the hypothesis that the regressing corpus luteum of pregnancy suppresses folliculogenesis in the ipsilateral ovary after parturition. Dairy cows were treated with prostaglandin F2alpha between 190 and 220 days of gestation to cause luteolysis without inducing parturition (n = 14) or were untreated controls (n = 32).