Oxytocin and bovine parturition: a steep rise in endometrial oxytocin receptors precedes onset of labor.

Oxytocin receptors were measured in myometrium and intercaruncular endometrium of cows during pregnancy and parturition. Concentrations of estradiol-17 beta, estrone, and progesterone in peripheral blood were also measured. Receptor concentrations in the endometrium rose almost 200-fold from Day 20 to term (p < 0.0001, ANOVA), from 40 +/- 11 to 7300 +/- 1430 fmol/mg protein. Myometrial receptor concentrations increased 10-fold from 180 +/- 36 fmol/mg on Day 20 to 1850 +/- 360 fmol/mg protein at term (p < 0.0001, ANOVA). During labor, endometrial receptors (6600 +/- 1300 fmol/mg) remained at prelabor values, whereas myometrial receptor concentrations had decreased to 1190 +/- 316 fmol/mg (not significant) and declined further postpartum. Plasma concentrations of progesterone declined from 4-5 ng/ml to about 2 ng/ml between Days 250 and 282 and dropped to < 0.2 ng/ml shortly before delivery. Plasma concentrations of estrone and estradiol-17 beta were below 10-20 pg/ml until Day 230. Estrone concentrations were significantly (p < 0.05) increased by Day 250 and estradiol-17 beta by Day 270, and then both rose rapidly. During labor, plasma estrone was 1135 +/- 245 pg/ml and plasma estradiol-17 beta was 226 +/- 131 pg/ml. The molar ratio of estrone and estradiol-17 beta to progesterone rose from less than 0.01 to 4.4 during labor, and was correlated with oxytocin receptor concentrations in endometrium (r = 0.5160, p < 0.001), but not those in myometrium (r = 0.0122). The regulation of oxytocin receptors by ovarian hormones in the two tissues may therefore differ.(ABSTRACT TRUNCATED AT 250 WORDS)     

A critical period in the onset of parturition in rats and uterine sensitivity to estradiol and progesterone

The purpose of this paper was to impair normal parturition in rats in order to measure tissue levels of progestins and estrogens and compare these results with those of normal parturition in rats. Abnormal parturition was obtained by injection of isotonic saline into the uterine lumen of pregnant rats at the end of pregnancy or by handling the uterus. After each of these treatments on day 21 of pregnancy, parturition was impaired in 70 to 98% of the rats. When the treatments were carried out earlier or later in pregnancy, there was little or no impairment. Our results indicate transient discrepancies in plasma and tissue levels of steroids 6 h after treatment on day 21: 20 alpha-HP concentrations increased in treated rats compared to controls (uteri: 470%; p less than 0.01; ovaries: 89%; p less than 0.001); concomitantly, there was a sharp rise in P concentrations in uteri (+ 74% : p less than 0.05) and ovaries (+ 52%; p less than 0.05). Inversely, uterine concentrations of E2 decreased 6 h after treatment compared to controls (- 30%; p less than 0.05), although there was a transient rise of E2 in the ovaries (+ 30%; p less than 0.05). Twenty-four hours later, E2 concentrations were always lower in the uteri (- 30%; p less than 0.01). No change in E2 levels was noted in the uteri or ovaries of either the control or treated rats. The physiological significance of these changes and their consequences on uterine reactivity at term have been discussed. The data demonstrate that day 21 was a critical period in the parturient activity of the rat uterus which appears to be primarily affected by uterine levels of E2 between days 21 and 22 of pregnancy.     

Liraglutide treatment effects on rat ovarian and uterine tissues

Liraglutide is a Glucagon-like peptide-1 (GLP-1) analogue used for the treatment of type II diabetes mellitus and obesity. The present study aimed at investigating the effect of Liraglutide in ovarian and uterine tissues in albino rats. 30 female rats were divided into 3 groups, 10 rats each. Group (I) served as control group, group (II) animals administrated therapeutic doses of liraglutide for 5 weeks and group (III) animals were injected with Liraglutide as the pervious group. Then they were left for 2 weeks after drug termination as a recovery period. The biochemical results showed a decrease in the female reproductive hormones profile, luteinizing hormone (LH), follicle stimulating hormone (FSH), estrogen (ER), progesterone (PR) and an increase in the level of testosterone (T). Liraglutide administration caused a significant decrease in the antioxidant markers, glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and a significant increase in the activity of malondialdehyde (MDA). The histopathological examination revealed apoptosis of granulosa cells of different types of follicles with an increase in atretic and disorganized follicles. Vacuolar degenerative changes, and Atrophied muscle with sever inflammatory cell infiltrate in endometrium with congested, dilated blood vessels could be detected in uterine tissues. However, most of the deleterious effects of liraglutide decreased after drug discontinuation. In this study, we clarify the harmful effect of the liraglutide on ovarian and uterine tissues, thus potentially causing reproductive health malfunction and reducing the chances of pregnancy.     

Endocrine regulation of the onset of parturition in rats

The endocrine regulation of parturition exhibits several interspecies differences. Among the endocrine parameters considered to be the most important ones from the point of view of the regulation of parturition the concentration of oestrogens (oestradiol, oestriol and oestrone), progesterone, PGF2 alfa and its degradation product PGFM, was determined in both peripheral and uterine venous blood by RIA method in rats starting from the 15th day of pregnancy to the 3rd or 4th day following parturition. In the pregnant rat oestriol could only be detected on the day of parturition (21th day). Concentrations of oestriol and oestradiol were the highest on the day of parturition. An opposite tendency could be observed as far as progesterone concentration was concerned, i.e., the concentration decreased gradually from the 15th day of pregnancy onwards and the lowest value was reached on the day of parturition both in peripheral and uterine venous blood. PGF2 alfa and PGFM concentrations in the uterine vein increased gradually from the 15th day of pregnancy and the highest value could be detected peri partum. Our data, in accordance with those of others support the idea that the hormones investigated are involved in the process of parturition, i.e., characteristic changes of oestrogens, progesterone and prostaglandin levels ensue in the rat prior to parturition.     

Oxytocin modulates selection of allies in intergroup conflict

In intergroup competition and conflict, humans benefit from coalitions with strong partners who help them to protect their in-group and prevail over competing out-groups. Here, we link oxytocin, a neuropeptide produced in the hypothalamus, to ally selection in intergroup competition. In a double-blind placebo-controlled experiment, males self-administered oxytocin or placebo, and made selection decisions about six high-threat and six low-threat targets as potential allies in intergroup competition. Males given oxytocin rather than placebo viewed high-threat targets as more useful allies and more frequently selected them into their team than low-threat targets.     

A search for associations between weather and the onset of human parturition

Weather data were examined for association with hospital records indicating the time at which pregnant women at term first experienced labor contractions (onsets). There is a considerable advantage, compared with mortality and morbidity, to using this response to infer weather influences. Three tests were used. First, the time series of daily onsets was analyzed to determine if characteristics known to exist in time series of weather data — variability and persistence — were evident in daily onsets. Second, the frequency distributions of nine weather variables were stratified, mostly by terciles, and onset means calculated for each of these divisions. Response means much different from average were then used to specify the nature of weather at such times. Third, the weather data were organized as weather types — pre- and post-cold frontal and general cold frontal — and onsets at these times were compared with those at non-frontal times. The time series characteristics were not found, but the other analysis revealed subsets of days on which onsets were above average, and in some cases the results were statistically significant. One such subset consists of winter days with low pressure, temperature markedly lower than the day before, and high wind speeds. On such days onsets were 34% above average. They were also above average during the 48 hours before and after cold front passage, and especially so in the 12 hours prior to the front. These findings constitute a weak, but statistically significant indication that human parturition is influenced by weather. Follow-up studies are urged.     

Oxytocin enhances onset of lactation among mothers delivering prematurely.

In a double-blind group sequential trial the efficiency of an oxytocin nasal spray in enhancing lactation was studied during the first five days after delivery in women who had given birth prematurely. The cumulative volume of breast milk obtained between the second and fifth days after delivery was 3.5 times greater in primiparas given oxytocin than in primiparas given placebo. There was no significant difference in the composition of the milk between the untreated women and those given oxytocin. The results of this study show that oxytocin nasal spray is an effective and safe means of enhancing lactation in women using a breast pump.     

Capillary morphogenesis protein-2 is required for mouse parturition by maintaining uterine collagen homeostasis

Capillary morphogenesis protein-2 (CMG2) functions as an anthrax toxin receptor that plays an essential role in anthrax pathogenesis. Although mutations in CMG2 have been identified to cause two human autosomal recessive disorders, Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis, both characterized by excess hyaline material deposition in connective tissues, the physiologic function of CMG2 remains elusive. To study the roles of CMG2 in normal physiology, here we performed detailed histological analyses of the CMG2-null mice we generated previously. While no morphological or histological defects were observed in CMG2(-/-) male mice, CMG2(-/-) female mice were unable to produce any offspring due to a defect in parturition. We found that deletion of CMG2 resulted in a diffuse deposition of collagen within the myometrium of CMG2(-/-) females, causing remarkable morphological changes to their uteri. This collagen accumulation also led to loss of smooth muscle cells in the myometrium of CMG2(-/-) mice, apparently disabling uterine contractile function during parturition. As a consequence, even though pregnant CMG2(-/-) mice were able to carry the gestation to full term, they were unable to deliver pups. However, the fully-developed fetuses could be successfully delivered by Cesarean section and survived to adulthood when fostered. Our results demonstrate that CMG2 is not required for normal mouse embryonic development but is indispensable for murine parturition. In parallel to its role in anthrax toxin binding and internalization, herein we provide evidence that CMG2 may function as a collagen receptor which is essential for maintaining collagen homeostasis in the uterus.     

Ultrasonographic study of ovarian function during early pregnancy and after parturition in the ewe

Transrectal ultrasonography of ovaries was performed in 11 ewes from Days 10 to 26 and on Day 30 of pregnancy to record the number, size, and position of ovarian follicles > or = 3 mm in diameter and corpora lutea (CL). Transrectal and/or transabdominal ultrasonography of the uterus was performed on Days 10 to 26, 30, 35, 40, 45 and 50 of gestation to ascertain the number and position of the conceptuses. In a second experiment, ultrasonography was conducted in 15 ewes on Days 10, 25, 30, 45 and 50 of pregnancy and from Days 13 to 29 after parturition. Ovarian data were classified into ovaries without CL (Group 1), ovaries with the CL in 1 ovary (Group 2), and ovaries with the CL in both ovaries during pregnancy (Group 3). In early pregnant ewes, the total number of follicles and the diameter of all follicles > or = 3 mm were smaller (P < 0.05) in the CL-bearing ovaries (both Group 2, n = 7 and Group 3, n = 8) than in the non-CL-bearing ovaries (Group 1, n = 7), while the largest follicle diameter was significantly smaller in Group 3 than in Group 1 or 2 ovaries. The number of 3-mm follicles in Group 2 ovaries was lower (P < 0.05) than in Group 1 or 3 ovaries, but the mean number of follicles > or = 5 mm in diameter was significantly lower in Group 3 than in Group 1. The total luteal volume per ovary was higher (P < 0.001) in Group 2 than in Group 3 ovaries of early pregnant ewes. The total follicle diameter and the number of follicles growing from 3 to > or = 5 mm in diameter was lower (P < 0.05) for Group 2 ovaries of ewes that carried twins (n = 3) compared with Group 2 ovaries from ewes with singletons (n = 4). There were no differences in follicular dynamics between Group 3 ovaries and the ovaries of Group 2 in ewes that carried twins. No follicles > 3 mm were seen in the ovaries of postpartum ewes that contained CL during gestation, until Days 21 and 25 postpartum for Groups 2 (n = 10) and 3 (n = 8), respectively, and follicles reaching > or = 5 mm in diameter were detected in only 2 ovaries (Group 2), on Days 27 and 28 postpartum, respectively. We conclude that during early pregnancy in ewes there is a suppression of antral follicle growth which appears to be exerted primarily by the developing conceptus but remains confined to CL-bearing ovaries. Residual local inhibition of follicular development extends into the postpartum period.     

Diet-induced hyperlipidemia in cattle modifies the intrafollicular cholesterol environment, modulates ovarian follicular dynamics, and hastens the onset of postpartum luteal activity.

Three experiments were conducted with female cattle during the postpartum period and during the estrous cycle to examine the effects of diet-induced hyperlipidemia on lipoprotein-cholesterol and triglyceride (TG) metabolism, ovarian follicular dynamics, and incidence of postpartum luteal activity. Dietary-lipid effects were examined independently of metabolizable energy intake. Feeding a high-lipid (HL) diet (8% total lipid) for the first 3 wk of the puerperium (Experiment 1) increased (p less than 0.0001) the concentration of total cholesterol and high-density lipoprotein-cholesterol (HDL-CH), but not TG, within follicular fluid (FF) of estrogen-active (E-A) and inactive (E-I) follicles. Increases (1.4- to 1.7-fold) were similar in proportion to those observed in peripheral blood serum, but absolute concentrations were about 45% of that in serum. Greater than 95% of the cholesterol in FF was HDL-CH, with a greater (p less than 0.06) proportion of HDL-CH sequestered by E-A compared to E-I follicles. The HL diet increased (p less than 0.06) the number of medium-sized (3.1-9.9 mm) follicles present at ovariectomy 19-21 days postcalving and increased (p less than 0.03) concentrations of FF androstenedione in E-I follicles 5-fold. Granulosa cells from preovulatory follicles (Experiment 2) of heifers fed HL diets secreted 2.1- to 3.5-fold greater (p less than 0.03) quantities of pregnenolone and progesterone in vitro. Finally, feeding HL supplements to postpartum range cattle for 30 days increased (p less than 0.05) the incidence of ovarian luteal activity by 18% (Experiment 3). Shifts in lipid metabolic status modify reproductive potential in cattle, independently of dietary energy intake.     

The effects of ovarian hormones and ACTH on uterine defense to Corynebacterium pyogenes in cows

Ovariectomized cows were treated with either estrogen, progesterone or adrenogorticotropic hormone (ACTH). Each cow's uterus was inoculated with 1x10(6)Corynebacterium pyogenes organisms. The cows were evaluated by rectal examination for signs of uterine infection. Peripheral leukocytic phagocytosis was determined by chemiluminescence at the beginning (Day 4) and end (Day 21) of the experiment. Uterine cultures were obtained at the end. None of the estrogen-treated cows developed signs of uterine infection, but all the other cows did develop uterine disease. All the infected cows showed clinical improvement at the experimental end (Day 21). There were no differences between groups for leukocytic phagocytosis on Day 4, but on Day 21, values for progesterone-treated and control cows were similar but greater than those for estrogen or ACTH-treated cows, which were similar. Leukocytic phagocytosis values for all cows were lower on Day 21 than on Day 4. Most of the estrogen- and ACTH-treated cows had negative intrauterine cultures on Day 21 while most of controls and progesterone-treated cows had positive cultures.     

CD43 modulates severity and onset of experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis characterized by infiltration of activated CD4(+) T lymphocytes into tissues of the CNS. This study investigated the role of CD43 in the induction and progression of EAE. Results demonstrate that CD43-deficient mice have reduced and delayed clinical and histological disease severity relative to CD43(+/+) mice. This reduction was characterized by decreased CD4(+) T cell infiltration of the CNS of CD43(-/-) mice but similar numbers of Ag-specific T cells in the periphery, suggesting a defect in T cell trafficking to the CNS. The absence of CD43 also affected cytokine production, as myelin oligodendrocyte glycoprotein (MOG) 35-55-specific CD43(-/-) CD4(+) T cells exhibited reduced IFN-gamma and increased IL-4 production. CD43(-/-) CD4(+) MOG-primed T cells exhibited reduced encephalitogenicity relative to CD43(+/+) cells upon adoptive transfer into naive recipients. These results suggest a role for CD43 in the differentiation and migration of MOG(35-55)-specific T cells in EAE, and identify it as a potential target for therapeutic intervention.     

The effect of experimentally induced hypocalcaemia on uterine activity at parturition in the ewe

The effect of hypocalcaemia experimentally induced by the intravenous infusion of ethylene-diamine tetraacetic acid, disodium salt (Na(2)EDTA) upon myometrial activity at parturition was studied in eleven ewes. Infusions of Na(2)EDTA were performed during first stage of labour (three animals), second stage (four animals), third stage (three animals) and postpartum (two animals); one in the latter group had been previously treated during second and third stages. Uterine activity was recorded using balloon-tipped catheters surgically implanted into the uterus and was expressed in Montevideo Units (M.U.). Plasma calcium (nonchelated) concentrations were monitored throughout the infusion. Induced hypocalcaemia resulted in a reduction of the activity of the uterus when Na(2)EDTA was administered during the first stage of labour. In the ewes infused during the second stage of labour, there was difficulty in reducing the activity of the uterus and, consequently, in delaying parturition. Reduction in uterine activity was easier in the ewes infused during the third stage of labour and during postpartum. Uterine activity started decreasing when plasma calcium concentrations were 6.6 and 7.1 mg/100 ml in the ewes infused during third stage of labour and postpartum, respectively, compared with 4.9 mg/100 ml in those infused during first stage of labour; the difference between this last group and the first two was significant (p < 0.05). After the end of the infusion, the plasma calcium started rising and normal uterine activity quickly resumed.