The lack of impact of peri-implantation or late gestation nutrient restriction on ovine fetal renal development and function.

Unbalanced nutrition during critical windows of development is implicated in determining the susceptibility to hypertension and cardiovascular disease in adult life, but the underlying mechanisms during fetal life have not been fully elucidated. We investigated the effects of moderate nutritional restriction during critical windows in gestation on late gestation fetal sheep growth, cardiovascular and renal renin-angiotensin system function. Ewes were fed 100% nutrient requirements (control), or 40-50% nutrient requirements during the peri-implantation period (1-31 days gestation (dGA), PI40 and PI50), or 50% nutrient requirements in late gestation (104-127 dGA). At 125 ± 2 dGA, fetal cardiovascular and renal function were measured at baseline, and during frusemide, angiotensin II (Ang II), phenylephrine and hypoxia challenges. Maternal undernutrition had no effect on fetal biometry, kidney weight, nephron number, basal cardiovascular function or cardiovascular and renal responses to frusemide. Fetal blood pressure response to Ang II was blunted in PI50 (P < 0.05), but not in PI40 groups. There was no difference between groups in the cardiovascular or endocrine response to hypoxia. The lack of effect of moderate undernutrition within key developmental windows of fetal kidney development on fetal renal structure and function suggests that renal mechanisms do not underlie our previous observations of cardiovascular dysfunction in adulthood following early-life undernutrition.

The relationship between uterine pathogen growth density and ovarian function in the postpartum dairy cow.

In cattle, the first postpartum dominant follicle grows slower and produces less oestradiol in animals with high numbers of bacteria contaminating the uterine lumen. However, only bacteria that are uterine pathogens are correlated with severe clinical disease and an increased inflammatory response. It is unknown whether the effect on the ovary in relation to uterine bacterial contamination is associated with the presence of recognised uterine pathogens. Therefore, the present study examined the relationship between pathogenic bacteria in the postpartum uterine lumen, follicle growth and function and the formation of a competent corpus luteum. In addition, peripheral plasma concentrations of immune mediators were quantified. Swabs were collected from the uterine lumen of cattle on day 7 postpartum. Bacteria were cultured and identified and bacterial growth was scored semi-quantitatively. Animals were categorized into high or low recognized uterine pathogen contamination groups based on the number of colonies. Ovarian structures were monitored by daily transrectal ultrasonography and blood samples were collected. In animals with high numbers of uterine pathogens on day 7 postpartum, the diameter of the first postpartum dominant follicle was smaller and plasma oestradiol concentrations were lower. In addition, these animals had smaller corpora lutea, which produced less progesterone. Furthermore, animals with a high day 7 uterine pathogen growth density had higher peripheral concentrations of acute phase proteins. Thus, contamination of the uterus with recognized uterine pathogens is associated with ovarian dysfunction during the postpartum period. Furthermore, infection results in an increase in the production of inflammatory mediators.

Effect of intrauterine administration of oestradiol on postpartum uterine bacterial infection in cattle.

After parturition fewer first dominant follicles are selected in the ovary ipsilateral to the previously gravid uterine horn in cattle. However, the presence of a large oestradiol-secreting follicle in the ipsilateral ovary is a predictor of fertility, possibly due to a localised effect of oestradiol which increases the rate of elimination of the ubiquitous uterine bacterial contamination that occurs after calving. The present study tested the hypothesis that oestradiol reduces uterine bacterial contamination when administered into the uterine lumen around the expected time for selection of the first postpartum dominant follicle. Animals were infused with saline (n=15) or 10mg oestradiol benzoate (n=15) into the previously gravid uterine horn on Days 7 and 10 postpartum. Peripheral coccygeal blood samples were collected daily and oestradiol concentrations measured by radioimmunoassay (RIA). Uterine lumen swabs were collected 7, 14 and 21 days postpartum for aerobic and anaerobic culture, bacteria were identified and growth scored semi-quantitatively. Plasma oestradiol concentrations were higher for treated animals between Days 7 and 14 (1.4+/-0.1 versus 2.0+/-0.2 pg/ml, P<0.05). Control animals had a similar bacterial growth score on Days 7 and 14, with a lower value on Day 21 (5.7+/-1.0 and 6.1+/-0.7 versus 0.3+/-0.1, P<0.05). However, treated animals had a surprising higher bacterial load on Day 14, than on Days 7 or 21 (7.1+/-0.9 versus 4.0+/-0.6 or 3.6+/-0.6, P<0.05). The increased score was attributable to more pathogens associated with endometritis on Day 14 than Day 7 (5.1+/-1.0 versus 2.5+/-0.5, P<0.05), in particular Prevotella melaninogenicus (1.5+/-0.5 versus 0.7+/-0.2, P<0.05) and Fusobacterium necrophorum (1.5+/-0.4 versus 0.3+/-0.2, P<0.05). In conclusion, administration of oestradiol into the uterine lumen surprisingly increased uterine pathogenic anaerobic bacterial contamination. Thus, it is unlikely that increased fertility associated with a first dominant follicle in the ipsilateral ovary is a consequence of the elimination of bacterial contamination by ovarian oestradiol.

The effect of oestradiol on postpartum uterine involution in sheep.

The present study tested the hypothesis that ovarian oestradiol increases the rate of uterine involution after parturition in sheep. The day after parturition, ewes were randomly assigned as un-operated controls (n=5), or a 3 cm silastic implant containing oestradiol (n=8) or empty (n=7) was sutured within the bursa of the ovary ipsilateral to the previously gravid uterine horn. Blood samples were collected daily for measurement of PGFM and acute phase proteins until 17 days postpartum when the ewes were slaughtered and the genital tract was collected. There was no consistent effect of treatment group on uterine involution determined by the collagen density, dry matter content, width, length, or weight of the genital tract. Furthermore, there was no evidence of a localised effect of oestradiol on involution as there were no significant differences between the previously gravid and non-gravid uterine horns. However, oestradiol-treated ewes had lower plasma concentrations of 15-keto-13,14-dihydro-prostaglandin F2alpha (P<0.01), alpha1-acid glycoprotein (P<0.05) and ceruloplasmin (P<0.001); but, not haptoglobin. These observations could reflect a direct effect of oestradiol on inflammatory mediator synthesis or secretion because, in the absence of parallel physical measurements, it is unlikely that these observations reflect a beneficial effect of treatment on uterine health.

Effect of postpartum manual examination of the vagina on uterine bacterial contamination in cows.

Twenty-one days after they had calved, the vaginas of 34 cows were examined with a clean gloved hand, and 26 cows were left unexamined. Swabs were collected from the lumen of the uterine body of the cows on the same day and seven days later; bacteria were identified by aerobic and anaerobic culture, and bacterial growth was scored semi-quantitatively. On the same days, blood samples were collected and the concentrations of acute phase proteins were measured, and the diameters of the cows' uterine horns were measured by transrectal ultrasonography. The vaginal examinations did not result in uterine bacterial contamination or an acute phase protein response, and they did not affect the diameters of the uterine horns.

Influence of uterine bacterial contamination after parturition on ovarian dominant follicle selection and follicle growth and function in cattle.

First postpartum dominant follicles are preferentially selected in the ovary contralateral to the previously gravid uterine horn. The aim of the present study was to test the hypothesis that uterine bacterial contamination alters the location of ovarian follicle emergence and selection, and inhibits follicle growth and function. Swabs were collected from the uterine body lumen of cattle on days 7, 14, 21 and 28 after parturition. Bacteria were identified by aerobic and anaerobic culture; bacterial growth was scored semiquantitatively and animals were categorized into standard or high bacterial contamination categories on the basis of the number of colonies detected. Follicular growth and function were monitored by daily transrectal ultrasonography, and estimation of plasma FSH, oestradiol and progesterone concentrations. There was no effect of bacterial contamination on plasma FSH concentration profiles or emergence of the ovarian follicle wave. When uterine bacterial growth scores were high on day 7 or day 21 after parturition, fewer first (1/20 versus 15/50; P < 0.05) or second (1/11 versus 13/32; P < 0.05) dominant follicles were selected in the ipsilateral compared with the contralateral ovary, respectively. The diameter of the first dominant follicle was smaller in animals with a high day 7 bacterial score (P < 0.001), dominant follicle growth was slower (P < 0.05) and oestradiol secretion was decreased (P < 0.05). The present study provides evidence for an effect of the uterus on the ovary after parturition, whereby uterine bacteria have a contemporaneous localized effect on ovarian follicle selection and subsequent growth and function, but not on initial emergence.

The effects of endometrial scarification on uterine steroid receptors, bacterial flora and histological structure in the bitch.

Following laparotomy, the endometrium of six nulliparous Beagle bitches was scarified at the base of one uterine horn during early metoestrus, when the peripheral plasma P(4) concentration was >10 ng/ml; intrauterine swabs were taken at the same time for bacteriological culture. Twenty-one days later, a bilateral ovariohysterectomy was performed and segments of the scarified and non-scarified parts of the tubular genital tract removed; at the same time, swabs were taken from the uterine lumen. Tissue samples were collected and examined for histopathological structure, and the presence of nuclear oestrogen (ER) and progesterone (PR) receptors using an immunocytochemical method. The immunoreactivity was scored semiquantitatively, incorporating both the intensity and distribution of specific staining of the receptors using a simplified histoscore (H-score). All uterine swabs were sterile, and in three of the six bitches there were noticeable changes with distension of the uterine lumen with secretions and debris and distension of the endometrial gland ducts of the scarified uterine segment. There were no statistically significant differences in the H-scores of ER or PR between scarified and non-scarified segments, except for PR H-scores in the glandular epithelium where the values for the scarified were significantly higher than for the non-scarified endometrium (mean+/-S.E.M. is 129.9+/-22.8 versus 59.5+/-12.6; P<0.05). Thus, trauma can modify the structure of the endometrium and the characteristics of the PR. Whether changes in PR expression are involved in the pathogenesis of CEH/pyometra in the bitch could not be ascertained from this study.

Undernutrition during the first half of gestation increases the predominance of fetal tissue in late-gestation ovine placentomes.

OBJECTIVE: To investigate, in sheep, the effects of maternal undernutrition during the first half of pregnancy on placental growth and development and fetal growth. STUDY DESIGN: Six ewes (R) were subjected to a 15% reduction in nutrient intake for the first 70 days of gestation and thereafter received the recommended daily intake. Another group of six ewes (C) received the recommended daily intake throughout pregnancy. At 130 days gestation the ewes were killed and morphological and morphometrical measurements were carried out on the placenta and fetus. RESULTS: Undernutrition resulted in a significant alteration in placental morphology, which was seen as increased growth of the fetal side of the placenta in R animals. However, fetal size in late gestation was not affected by the undernutrition, suggesting that placental adaptation was successful in maintaining fetal growth. CONCLUSION: Placental adaptations, including changes in gross morphology, may preserve fetal growth if maternal undernutrition is not severe. The mechanisms remain to be elucidated.

Acute phase protein responses to uterine bacterial contamination in cattle after calving.

Repeated ultrasonographic examinations and collections of blood samples and uterine lumenal swabs between seven and 28 days after calving were used to examine the relative effects of bacterial contamination and involution of the uterus on the concentrations of acute phase proteins in the blood of 26 dairy cows. The severity of bacterial contamination, as determined by the total bacterial growth score, was a significant variable for the concentrations of the acute phase proteins alpha1-acid glycoprotein (P < 0.0001), haptoglobin (P < 0.05) and ceruloplasmin (P < 0.0001). In addition, the concentrations of alpha1-acid glycoprotein and ceruloplasmin were increased in the cows from which Escherichia coli (P < 0.0001) and Arcanobacterium pyogenes (P < 0.05), respectively, were isolated from the uterine lumen. Uterine involution, as determined by the decreasing diameter of the previously gravid uterine horn, was associated with a decrease in the concentrations of alpha1-acid glycoprotein (P < 0.005), haptoglobin (P < 0.05) and ceruloplasmin (P < 0.01). However, the response of the acute phase proteins to bacterial contamination was independent of the day on which the samples were collected, indicating that their concentrations were increased by bacterial contamination in addition to the changes associated with uterine involution.

Changes in the weight, collagen concentration and content of the uterus and cervix of the ewe during pregnancy.

The dry and wet weights of the uterus (caruncular and intercaruncular areas) and cervix were measured in non-pregnant (n = 5) and pregnant (n = 25) ewes post mortem; for the latter, five were obtained for each of the 5 months of gestation. The total collagen tissue content was measured in both areas of the uterus and cervix by hydroxyproline analysis and image analysis of Haematoxylin-Van Gieson stained tissue sections. Both wet and dry uterine weights increased significantly with gestational age (P < 0.001). The water content of uterine and cervical tissue remained constant, at between 83 per cent to 85 per cent and 76 per cent to 80 per cent, respectively. There was a close correlation between the two methods used to determine the collagen content (r = 0.96, P < 0.001), and between the increasing weight of the uterus during pregnancy and the total collagen content of tissues (r = 0.97, P < 0.001). At all stages, the total collagen content of the cervix [mean (SEM) 96.2 (5.4) mg g(-1)] was significantly greater (P < 0.001) than that of the caruncular mean [mean (SEM) 24.3 (1.4) mg g(-1)], and the intercaruncular areas [mean (SEM) 29.0 (1.0) mg g(-1)]. The changes in uterine and cervical weights and collagen content of the tissues were similar to those reported in other related species.

Cystic endometrial hyperplasia/pyometra in dogs: a review of the causes and pathogenesis.

In this review the roles of endogenous and exogenous steroid hormones, steroid receptors, spontaneously occurring and experimentally induced genital tract infection, and endometrial trauma in the cause and pathogenesis of cystic endometrial hyperplasia/pyometra in bitches are considered. It is postulated that intrauterine bacteria, which ascend from the vagina during pro-oestrus and oestrus, induce the disease during metoestrus by acting on the progesterone-primed endometrium directly via toxin production, or indirectly by the release of inflammatory mediators. The lesion can be produced by endometrial trauma in a sterile uterus without the systemic effects associated with the disease. There is no association with premature or increased progesterone concentrations at the time that the disease is normally diagnosed in mid- to late metoestrus; however, such aberrant endocrine changes cannot be excluded from involvement in the pathogenesis of this disease, as there are no data from bitches preceding the onset of clinical signs. Expression of oestrogen and progesterone receptors are modified by endogenous steroid hormones but there is no clear evidence that changes in these receptors are involved in the pathogenesis of the disease; receptor expression can be modified by exogenous hormones.

The influence of ovarian activity and uterine involution determined by ultrasonography on subsequent reproductive performance of dairy cows.

The objective of this study was to test the hypothesis that a follicle >8 mm diameter in the ovary ipsilateral to the previously gravid uterine horn (PGUH), between 14 and 28 days postpartum, improves subsequent reproductive performance. Lactating Holstein-Friesian cows (n=284) in 3 commercial herds were examined using transrectal ultrasonography once between 14 and 28 days postpartum to determine associations between uterine and ovarian measurements and subsequent fertility. There were fewer cows with a corpus luteum in the ovary ipsilateral to the PGUH compared with the contralateral ovary (16.9% vs. 37.0%; P<0.001). In addition, in the ovary ipsilateral to the PGUH there were fewer follicles >5 mm diameter (mean +/- SEM; 0.69 +/- 0.06 vs. 1.02 +/- 0.06; P<0.001) and fewer animals with a follicle >8 mm diameter (26.1% vs. 49.6%; P<0.001). These differences between the ovaries ipsilateral or contralateral to the PGUH declined with increasing time between 14 and 28 days postpartum. The presence of a purulent vaginal discharge decreased the number of animals with a corpus luteum in the ovary contralateral to the PGUH (45/143 vs. 60/141; P<0.05), but not in the ovary ipsilateral to the PGUH. The presence of a follicle >8 mm diameter in the ovary ipsilateral to the PGUH was associated with a shorter calving to conception interval compared with animals without such a follicle (99.0 +/- 5.6 days, n=74, vs. 112.8 +/- 4.4 days, n=210; P<0.05). These observations raise an intriguing issue: how does this follicle affect subsequent fertility--does the follicle exert a local influence on the uterus, or vice versa?

Effect of maternal undernutrition in early gestation on ovine fetal blood pressure and cardiovascular reflexes.

Human epidemiological and animal experimental studies suggest that maternal undernutrition during pregnancy may alter cardiovascular development of the offspring. The extent to which these effects involve changes in fetal cardiovascular function and whether they are necessarily linked to reduced fetal growth is unknown. In sheep, we investigated the effect of a 15% reduction in maternal global nutrition for the first 70 days of gestation (term = 147 days) on fetal blood pressure development, baroreflex control of fetal heart rate (FHR), and cardiovascular responses to acute hypoxemia in late gestation. Basal mean arterial pressure (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and rate-pressure product (P < 0.001) were significantly lower in fetuses of nutritionally restricted ewes (R) compared with controls (C). FHR was not altered. The operating point for the fetal baroreflex was significantly lower in R fetuses compared with C (P < 0.01), but there was no difference between the groups in the cardiovascular response to hypoxemia. We conclude that mild maternal undernutrition alters fetal cardiovascular development, producing low blood pressure and resetting of baroreflex control mechanisms. This effect occurs without any changes in fetal growth or blood gas status.

Peripheral and intrauterine neutrophil function in the cow: the influence of endogenous and exogenous sex steroid hormones.

It has been accepted for many years that the susceptibility of the genital tract to infection is reduced during the follicular phase compared with the luteal phase of the estrous cycle. Since the role of intrauterine neutrophils is paramount in the elimination of bacteria, it can be hypothesized that these differences in resistance to infection could be mediated by differences in uterine-derived neutrophil function. In order to test this hypothesis two groups of cows were used in this study. Group 1 cows (n=5) were studied at estrus, diestrus, after ovariectomy, after exogenous estradiol and after progesterone treatment, at which time they underwent intrauterine infusion with 1% oyster glycogen (OG) and a bacterial-free filtrate (BFF) of Actinomyces genes (BFF), the latter having been recovered from a clinical case of endometritis; neutrophils were harvested by flushing from the lumen 15 to 18 h later. A peripheral blood sample was collected at the time of flushing for the assay of estradiol and progesterone for a WBC and differential count and for the harvesting of neutrophils using a Percoll single-stage discontinuous gradient. After the recovery of the cells they were re-suspended in HBSS. Group 2 (n=4) were infused with BFF during during all reproductive states as Group 1, but with OG only after ovariectomy and after treatment with progesterone and estradiol. Neutrophil chemotaxis was assessed by measuring their migration using a modified Boyden chamber and Zymogen-activated serum as a chemoattractant. Phagocytic activity was measured by determining the number of Candida albicans ingested by each neutrophil after incubation. The percentage of kill was determined using a radiometric assay in which C. albicans was labeled with L-(5-3H) Proline. Peripheral WBC concentration was not influenced by the reproductive state of the cow; however, the mean neutrophil concentration was significantly different between the reproductive states (P<0.001) and between individual cows (P<0.001). In Group 1, there was little difference in the function of the peripheral and uterine neutrophils, and while there were differences in all 3 aspects of neutrophil function from both sources between reproductive states and individual cows, of which some were statistically significant, there was no consistent pattern. In Group 2, neutrophils recovered after the infusion of BFF had poorer function compared with those recovered after the infusion of OG. There was no consistent influence of the reproductive state or individual animal. The hypothesis that the influence of the reproductive state of the cow on the resistance of the uterus to infection is mediated by the inherent differences in either peripheral or intrauterine neutrophil function was not supported by this study.

Ultrasonography of spontaneous lesions of the genital system of three rams, and their influence on semen quality.

Three young Suffolk ram lambs had lesions which rendered them reproductively unsound. One had a unilateral scrotal hernia, detected by palpation, and two had sperm granulomas which were detected by trans-scrotal ultrasonography at 18 to 20 weeks of age, before they could be detected by palpation. Changes in the lesions were monitored ultrasonographically at two-week intervals with a 7.5 MHz linear array transducer. On the day of each examination, semen was collected from the rams with sperm granulomas by using an artificial vagina, and their libido was assessed. Semen could rarely be collected from the third ram. Comparisons were made with similar data obtained from two normal rams. When the rams were 20 to 21 months of age, they were vasectomised on the normal side, so that the influence of the lesions on semen composition and libido could be assessed, and semen was collected and evaluated until they were euthanised at approximately 24 months of age, when the genital system was examined for gross lesions. The sperm granulomas changed in size (one of them increased in size by about 30 times) and echotexture over the 19-month period of the study, whereas the scrotal hernia, which contained omental fat, remained fairly constant. The libido of the two rams with sperm granulomas was comparable with the two normal controls. The total mean (sem) number of sperm in the ejaculates were 1.11 (0.10) x 10(9) and 2.03 (0.17) x 10(9) sperm/ml in the affected rams and 4.11 x 10(9) sperm/ml in the normal rams over the same period; the differences were significant (P<0.05). After unilateral vasectomy, the ejaculates from these two rams contained small numbers of dead spermatozoa, mostly with degenerate heads. Postmortem examination confirmed the gross lesions identified ultrasonographically.

Effect of maternal nutrient restriction in early gestation on responses of the hypothalamic-pituitary-adrenal axis to acute isocapnic hypoxaemia in late gestation fetal sheep.

Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic-pituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired O2 fraction (FI,O2). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.

Cardiovascular and hypothalamic-pituitary-adrenal axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation.

The effect of a 15% reduction in maternal nutrition for the first 70 days of gestation on cardiovascular and hypothalamic-pituitary-adrenal (HPA) axis responses to administration of corticotropin releasing hormone (CRH) + arginine vasopressin (AVP) was studied at 128 +/- 0.7 days gestation in fetal sheep and postnatally, at 85 +/- 4.5 days in young lambs. The effect on the fetal cardiovascular response to acute hypoxaemia was also examined. Under basal conditions, fetal heart rate (FHR) was reduced (P < 0.05) and basal femoral artery vascular resistance (FVR) was increased (P < 0.05) in fetuses of dietary-restricted (R) ewes compared with controls (C). Fetal mean arterial pressure (MAP) was similar in both groups. Femoral artery vascular resistance was also greater during hypoxaemia in R fetuses compared with C fetuses (P < 0.05), suggesting that chemoreflex mechanisms were augmented in the R group. The fetal ACTH response to CRH + AVP was similar in both groups. However, cortisol responses to CRH + AVP were smaller in R fetuses compared with C fetuses (P<0.05). Postnatally, basal MAP (P < 0.05), and ACTH (P < 0.01) and cortisol (P < 0.001) responses were greater in R lambs compared with C lambs. It was concluded that modest maternal undernutrition during pregnancy alters development of the cardiovascular system, producing elevated blood pressure in postnatal life. Development of the HPA axis is also altered, with reduced activity during fetal life, but increased activity postnatally. The data suggest that the HPA axis may play a role in mediating the elevation of MAP in R lambs.

Effect of maternal nutrient restriction in early gestation on development of the hypothalamic-pituitary-adrenal axis in fetal sheep at 0.8-0.9 of gestation.

The fetal hypothalamic-pituitary-adrenal (HPA) axis has numerous key roles in development. Epidemiological data have linked adverse prenatal nutrition with altered organ development and increased incidence of disease in adult life. We studied HPA axis development in resting and stimulated states in late gestation fetal sheep, following 15% reduction in maternal nutritional intake over the first 70 days of gestation (dGA). Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and response profiles for ACTH and cortisol were determined at 113-116 and 125-127 dGA after administration of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). At 126-128 dGA cortisol profiles were also determined following ACTH administration. Basal ACTH and cortisol concentrations were not different between C and R fetuses. In R fetuses, ACTH response to CRH+AVP was significantly smaller at 113-116 dGA (P<0.01), and cortisol responses were smaller at both 113-116 dGA (P<0.01) and 125-127 dGA (P<0.0001). Cortisol response to ACTH was also smaller in R fetuses (P<0.001). We conclude that, in late gestation fetal sheep, pituitary and adrenal responsiveness is reduced following modest maternal nutrient restriction in early gestation.

Oestrogen and progesterone receptors in the uterine wall of bitches with cystic endometrial hyperplasia/pyometra.

Fresh samples of uterine wall and peripheral plasma were obtained from 13 bitches of different breeds when they were treated for cystic endometrial hyperplasia/pyometra by ovariohysterectomy. The plasma samples were assayed for progesterone and 17beta-oestradiol, and the tissue samples were examined histopathologically and for the presence of oestrogen and progesterone receptors by an immunocytochemical method. The immunoreactivity was scored semiquantitatively, taking into account both the intensity and distribution of the specific staining of the receptors, by using a simplified scoring system. The scores for both oestrogen and progesterone receptors in the glandular epithelium were much lower, and in the endometrial stroma a mean (sd) score for oestrogen receptors was 46.0 (44.7) compared with 0 in comparable endometrial tissues from normal bitches at the same stage of the oestrous cycle.