Genetic analysis of retained placenta and its association with reproductive disorder, production, and fertility traits of Iranian Holstein dairy cows.

To facilitate breeding for improved resistance to the reproductive disorder of retained placenta (RP), genetic parameters were estimated for RP and its genetic correlation with other reproductive disorders as well as with production and fertility traits of Iranian Holstein dairy cows. Data were 154,048 lactation records collected between 2011 and 2018 from 59,610 Holstein dairy cows in 9 Iranian herds. Other reproductive disorders included dystocia, stillbirth, and twinning. Fertility records were available for days from calving to first service (DFS), days open (DO), number of inseminations per conception (NIC), and success of first insemination (SFI). Genetic parameters for RP were estimated using univariate linear and logistic animal models with ASREML software. The univariate linear animal model was used to implement bivariate analysis to investigate potential genetic correlations of RP with other reproductive disorders and with production and fertility traits. Heritability estimates for RP were low from both linear (0.031) and logistic (0.092) animal models. Estimated genetic correlations with RP were -0.04 for twinning, 0.32 for stillbirth, and 0.34 for dystocia, which indicates that selection against RP could indirectly select against dystocia and stillbirth. Estimated genetic correlations between RP and production traits (milk, fat, and protein yields) at 100, 200, and 305 d in milk ranged from -0.12 to -0.29; the greatest correlation (-0.29) was for the first 100 d in milk. A moderate positive genetic correlation (0.25) was found for RP and DO, DFS, and NIC, whereas a low negative genetic correlation (-0.09) was found between RP and SFI. The pedigree-based genetic analysis of RP showed that this trait has a low heritability, is linked to other reproductive disorders, and generally has an unfavorable relationship with production and fertility traits. Selection against RP can reduce the incidence of reproductive disorders and improve fertility and production traits.

Salivary cortisol as a non-invasive approach to assess stress in dystocic dairy calves.

The intensity and the magnitude of saliva cortisol responses were investigated during the first 48 h following birth in newborn dairy calves which underwent normal (eutocic, EUT, n = 88) and difficult (dystocic, DYS, n = 70) calvings. The effects of parity and body condition of the dam, the duration of parturition, the time spent licking the calf, the sex and birth weight of the calf were also analyzed. Neonatal salivary cortisol concentrations were influenced neither by factors related to the dam (parity, body condition) nor the calf (sex, birth weight). The duration of parturition and the time spent licking the calf also had no effect on salivary cortisol levels. Salivary cortisol concentrations increased rapidly after delivery in both groups to reach their peak levels at 45 and 60 min after delivery in EUT and DYS calves, respectively supporting that the birth process means considerable stress for calves and the immediate postnatal period also appears to be stressful for newborn calves. DYS calves exhibited higher salivary cortisol concentrations compared to EUT ones for 0 (P = 0.022), 15 (P = 0.016), 30 (P = 0.007), 45 (P = 0.003), 60 (P = 0.001) and 120 min (P = 0.001), and for 24 h (P = 0.040), respectively. Peak levels of salivary cortisol and the cortisol release into saliva calculated as AUC were higher in DYS than in EUT calves for the 48-h of the sampling period (P = 0.009 and P = 0.003, respectively). The greater magnitude of saliva cortisol levels in DYS calves compared to EUT ones suggest that difficult parturition means severe stress for bovine neonates and salivary cortisol could be an opportunity for non-invasive assessment of stress during the early neonatal period in cattle.

Ggps1 deficiency in the uterus results in dystocia by disrupting uterine contraction.

Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, resulting in neonatal morbidity and mortality; thus, there is an urgent need for novel therapeutic agents. Previous studies indicated that statins, which inhibit the mevalonate (MVA) pathway of cholesterol synthesis, can reduce the incidence of preterm birth, but the safety of statins for pregnant women has not been thoroughly evaluated. Therefore, to unambiguously examine the function of the MVA pathway in pregnancy and delivery, we employed a genetic approach by using myometrial cell-specific deletion of geranylgeranyl pyrophosphate synthase (Ggps1) mice. We found that Ggps1 deficiency in myometrial cells caused impaired uterine contractions, resulting in disrupted embryonic placing and dystocia. Studies of the underlying mechanism suggested that Ggps1 is required for uterine contractions to ensure successful parturition by regulating RhoA prenylation to activate the RhoA/Rock2/p-MLC pathway. Our work indicates that perturbing the MVA pathway might result in problems during delivery for pregnant females, but modifying protein prenylation with supplementary farnesyl pyrophosphate or geranylgeranyl pyrophosphate might be a strategy to avoid side effects.

Hyponatraemia reversibly affects human myometrial contractility. An in vitro pilot study.

BACKGROUND: In a previous study we found a significant correlation between dystocia and hyponatraemia that developed during labour. The present study examined a possible causal relationship. In vitro studies often use area under the curve (AUC) determined by frequency and force of contractions as a measure of myometrial contractility. However, a phase portrait plot of isometric contraction, obtained by plotting the first derivate of contraction against force of contraction, could indicate that bi-or multiphasic contractions might be less effective compared to the smooth contractions. MATERIAL AND METHODS: Myometrial biopsies were obtained from 17 women undergoing elective caesarean section at term. Each biopsy was divided into 8 strips and mounted isometrically in a force transducer. Seven biopsies were used in the first part of the study when half of the strips were immersed in the hyponatraemic study solution S containing Na+ 120 mmol/L and observed for 1 hour, followed by 1 hour in normonatraemic control solution C containing Na+ 136 mmol/L, then again in S for 1 hour, and finally 1 hour in C. The other half of the strips were studied in reverse order, C-S-C-S. The remaining ten biopsies were included in the second part of the study. Response to increasing doses of oxytocin (OT) in solutions S and C was studied. In the first part of the study we calculated AUC, and created phase portrait plots of two different contractions from the same strip, one smooth and one biphasic. In both parts of the study we registered frequency and force of contractions, and described appearance of the contractions. RESULTS: First part of the study: Mean (median) contractions per hour in C: 8.7 (7.6), in S 14,3 (13). Mean (SD) difference between groups 5.6 (4.2), p = 0.018. Force of contractions in C: 11.8 (10.2) mN, in S: 10.8 (9.2) mN, p = 0.09, AUC increased in S; p = 0.018. Bi-/multiphasic contractions increased from 8% in C to 18% in S, p = 0.001. All changes were reversible in C. Second part of the study: Frequency after OT 1.65 x 10-9 M in C:3.4 (2.9), in S: 3.8 (3.2), difference between groups: p = 0.48. After OT 1.65 x 10-7 M in C: 7.8 (8.9), increase from previous OT administration: p = 0.09, in S: 8.7 (9.0), p = 0.04, difference between groups, p = 0.32. Only at the highest dose of OT dose was there an increase in force of contraction in S, p = 0.05, difference between groups, p = 0.33. Initial response to OT was more frequently bi/multiphasic in S, reaching significance at the highest dose of OT(1.65 x 10-7 M), p = 0.015. when almost all contractions were bi/multiphasic. CONCLUSION: Hyponatraemia reversibly increased frequency of contractions and appearance of bi-or multiphasic contractions, that could reduce myometrial contractility. This could explain the correlation of hyponatraemia and instrumental delivery previously observed. Contractions in the hyponatraemic solution more frequently showed initial multiphasic contractions when OT was added in increasing doses. Longer lasting labours carry the risk both of hyponatraemia and OT administration, and their negative interaction could be significant. Further studies should address this possibility.

Expression of uterine oxytocin receptors and blood progesterone, 13,14-dihydro-15-Keto-Prostaglandin F2α, and ionized calcium levels in dystocic bitches.

This study aimed to examine the etiology of canine dystocia by measuring the relative expression of oxytocin receptor (OXTR) mRNA and the concentration of serum progesterone, plasma PGF2α metabolite (PGFM), and blood ionized calcium (iCa) near term and in dystocia. Altogether 58 bitches were included in this study, 41 of which underwent cesarean section (CS). The four CS groups were based on history: complete uterine inertia (CUI; n = 7), partial uterine inertia (PUI; n = 13), obstructive dystocia (OD; n = 10), and elective cesarean section (ECS; n = 11). An additional group of medically treated dystocia without CS (MD; n = 8) and a control group (C; n = 9) with normal parturition (without CS and medical treatment) were also formed. Blood samples were taken prior to CS or medical treatment. Progesterone concentrations were highest in the ECS and a significant difference (p < 0.05) was observed between the ECS and the OD and between the ECS and the combined dystocia (CUI, PUI, OD, MD) groups (COMB). Highest concentrations of PGFM was observed in the C, the difference being significant (p < 0.05) between the C and the ECS and between the C and the COMB group. The progesterone:PGFM ratio was significantly (p < 0.05) higher in the ECS than in the C and the COMB group. No significant difference (p > 0.05) was observed in iCa concentrations between the groups. Relative OXTR mRNA expression was evaluated with real-time PCR from full-thickness uterine samples taken from the incision site during CS. The expression was highest in the ECS and the difference in expression was significant (p < 0.05) between the ECS and the OD and between ECS and the combined dystocia (CUI, PUI, OD) groups (COMB2). The study supports previous reports of decreasing progesterone and increasing PGFM during prepartum luteolysis. Upregulation of OXTR occurs near term. In obstructive dystocia, a prolonged influence of oxytocin and uterine exhaustion may lead to downregulation of OXTR. Complete primary uterine inertia may have a different etiology as no clear decrease in OXTR was observed in CUI as in OD. It remains unclear if parturition ceases because of uterine inertia or if uterine inertia occurs because of ceased parturition and desensitization of receptors.

Laminin and Collagen IV: Two Polypeptides as Marker of Dystocic Labor.

Collagen IV and Laminin are localized in cells and tissue of numerous human organs including the uterus, where these polypeptides control either age changes, or uterus growth in pregnancy, or ripening and dilatation in labor. Authors examined the polypeptides distribution of collagen IV and Laminin in the human pregnant uterus, in normal and dystocic labor, to clarify their physiologic role, by distribution and/or their changes in prolonged dystocic labor. We collected lower uterine segment (LUS) fragments during cesarean section (CS); these biopsies were treated with basic morphological staining for the observation of microscopic- anatomic details. Other samples were processed with immunohistochemical staining for collagen IV and for membrane bound Laminin. All morphological and immunochemical results were analyzed with quantitative analysis of images and statistical analysis of data. Both Collagen IV and Laminin show changes in the pregnant uterus before 4 hours of full cervical dilatation in patients after 4 hours. All the three types of the human uterine cells, mucosal, submucosal and smooth muscular cells, are more reduced in LUS after 4 hours of cervical dilatation in dystocic labor. The connective tissues (including fibroblast) show the most evident changes in the dystocic LUS, collagen IV and laminin changes during cervical dilatation in prolonged dystocic labor, with a decreased elasticity with increased roughness and dryness. The LUS anatomical modifications during labor can be the cause of pathological changes in protracted dystocic labor. In the dystocic labor that lasts more than 4 hours from the complete cervical ripening and dilatation, the laminin and collagen IV concentration reduces in the LUS tissue. In dystocic labor, delivery should be completed before the 3 hours of full dilation, to avoid a reduction of laminin and collagen IV and a worsening of LUS healing for the next pregnancy.

Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term.

OBJECTIVE: We sought to assess amniotic fluid lactate (AFL) at diagnosis of spontaneous labor at term (≥37 weeks) as a predictor of labor disorders (dystocia) and cesarean delivery (CD). STUDY DESIGN: This was a single-institution, prospective cohort study of 905 singleton, cephalic, term (≥37 weeks) nulliparous women in spontaneous labor. A standard management of labor (active management of labor) including a standard oxytocin regimen up to a maximum dose of 30 mU/min was applied. AFL was measured using a point-of-care device (LMU061; ObsteCare, Stockholm, Sweden). Labor arrest in the first stage of labor was defined as the need for oxytocin when cervical dilatation was <1 cm/h over 2 hours and in the second stage of labor by poor descent and rotation over 1 hour. Standard statistical analysis included analysis of variance, Pearson correlations, and binary logistic regression. Unsupervised decision tree analysis with 10-fold cross-validation was used to identify AFL thresholds. RESULTS: AFL was normally distributed and did not correlate with age, body mass index, or gestation. Unsupervised decision tree analysis demonstrated that AFL could be divided into 3 groups: 0-4.9 mmol/L (n = 118), 5.0-9.9 mmol/L (n = 707), and ≥10.0 mmol/L (n = 80). Increasing AFL was associated with higher total oxytocin dose (P = .001), labor disorders (P = .005), and CD (P ≤ .001). Multivariable regression analysis demonstrated that women with AFL ≥5.0-9.9 mmol/L (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.06-2.39) and AFL ≥10.0 mmol/L (OR, 1.72; 95% CI, 1.01-2.93) were independent predictors of a labor disorder. AFL ≥5.0-9.9 mmol/L did not predict CD but multivariable analysis confirmed that AFL ≥10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73-6.46). AFL ≥5.0-9.9 mmol/L had a sensitivity of 89% in predicting a labor disorder and a sensitivity of 93% in predicting CD with a 97% negative predictive value. AFL ≥10.0 mmol/L was highly specific but lacked sensitivity for CD. There was no difference in birthweight of infants according to labor disorder and delivery method. CONCLUSION: AFL at diagnosis of labor in spontaneously laboring single cephalic nulliparous term women is an independent predictor of a labor disorder and CD. These data suggest that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol.

Association between birth conditions and glucose and cortisol profiles of periparturient dairy cows and neonatal calves.

Parturition in cattle is a stressful event for both the dam and the offspring. Stress and pain can alter the energy profile of calves and calving cows, producing a metabolic imbalance at birth. This study aimed to assess the effects of dystocia and oxytocin and calcium infusion on metabolic homeostasis in dairy cows and calves. Thirty Holstein cows and their calves were divided into three groups: an eutocia group (n=10), in which no calving assistance was needed; a dystocia group, which required mild-to-severe obstetric assistance (n=10); and a uterine inertia group, which was treated with oxytocin and calcium (n=10). To assess serum cortisol and blood glucose levels, blood samples were collected during the peripartum period from cows and during the first hour since birth from calves. All groups were hyperglycaemic following parturition. Infusion of oxytocin and calcium resulted in lower maternal glucose concentrations and lower levels of stress than in cows in the dystocia group. Birth condition was significantly associated with blood glucose and cortisol concentrations in calves. Glucose concentration was lower in calves born with oxytocin and calcium infusion than those born with fetal extraction. In conclusion, assisted calving with fetal extraction causes important metabolic changes for the dam and calf. Conversely, the practice of oxytocin and calcium infusion for hypotonic cows has no harmful effects on metabolic balance and can be safely employed as a medical treatment.

A validation study: assessing the reliability of the hand held StatStripXPress lactate meter to test lactate in amniotic fluid.

BACKGROUND: The level of lactate in amniotic fluid may provide useful clinical information when assessing whether a woman in labour is experiencing labour dystocia. If so, a rapid, reliable method to assess the concentration of amniotic fluid lactate at the bedside will be required in order to be clinically relevant. To assess efficacy, we compared the hand held StatStripXPreass lactate meter (Nova Biomedical) to the reference laboratory analyser ABX Pentra 400 (Horiba) in a controlled environment. Baseline biological lactate concentration was measured in triplicate and samples of a known quantity of thawed amniotic fluid spiked with lactate substrate (62 mmol/L) from the LDH12 kit (Roche, SUI) to yield a predetermined lactate concentration above baseline then measured in triplicate. Deming Regression was used to determine the linear agreement and a Bland Altman plot used to determine the paired agreement across the range of values. FINDINGS: The mean difference with Bland-Altman plot between hand held meter and lab instrument was -1.0 mmol/L (SD 3.0 mmol/L) with 95% CI limits of agreement between -6.9 mmol/L to 4.9 mmol/L. The Deming regression co-efficient or slope of agreement was 0.91 (SD of 0.21). CONCLUSION: The measurement of amniotic fluid lactate using the StatStripXPress hand held meter was reliable compared to reference laboratory methods for measuring lactate levels in amniotic fluid.

Endometrial cells sense and react to tissue damage during infection of the bovine endometrium via interleukin 1.

Cells generate inflammatory responses to bacteria when pattern recognition receptors bind pathogen-associated molecules such as lipopolysaccharide. Cells may also respond to tissue damage by sensing damage-associated molecules. Postpartum bacterial infections of the bovine uterus cause endometritis but the risk of disease is increased by tissue trauma triggered by dystocia. Animals that suffered dystocia had increased concentrations of inflammatory mediators IL-8, IL-1ß and IL-1α in vaginal mucus 3 weeks postpartum, but they also had more bacteria than normal animals. Ex vivo organ cultures of endometrium, endometrial cells and peripheral blood monocytes did not generate inflammatory responses to prototypical damage molecules, HMGB1 or hyaluronan, or to necrotic cells; although they secreted IL-6 and IL-8 in a concentration-dependent manner when treated with IL-1α. However, necrotic endometrial cells did not accumulate intracellular IL-1α or release IL-1α, except when pre-treated with lipopolysaccharide or bacteria. Endometrial cell inflammatory responses to IL-1α were dependent on the cognate receptor IL-1R1, and the receptor adaptor protein MyD88, and the inflammatory response to IL-1α was independent of the response to lipopolysaccharide. Rather than a typical damage-associated molecule, IL-1α acts to scale the inflammatory response in recognition that there is a combination of pathogen challenge followed by endometrial cell damage.

Amniotic fluid and blood lactate concentrations in mares and foals in the early postpartum period.

Amniotic fluid (AF) lactate concentration and time-dependent changes in blood lactate concentration in mares after parturition have never been evaluated. In this study, the venous blood lactate concentration of mares and foals during the first 72 h of the postpartum period was assessed, and the concentration of lactate in the AF collected during delivery and the utility of its measurement for evaluating the foal's health were investigated. This prospective observational study was carried out on mares attended at delivery. They were divided into mares delivering healthy (Group 1) and sick (Group 2) foals. The following samples were collected: AF and umbilical blood at delivery, mare's and foal's jugular blood every 12 hours from parturition until 72 h postpartum (T0-T72). Sixty-two mares were enrolled in Group 1 and 19 in Group 2. In Group 2, the survival rate was 68.4%. The median blood lactate of the foals at T0 was 3.60 mmol/L in Group 1 and 5.05 mmol/L in Group 2. The monitoring of the blood lactate concentration showed a significant time-dependent decrease from T24 in the foals (P < 0.01) and from T12 in the mares (P < 0.01). Lactate concentration over time was significantly different between healthy and sick foals (P < 0.01) but not between mares with normal and dystocic delivery (P = 0.08). A significant difference (P = 0.04) was detected as regards AF lactate concentration between Group 1 (median 14.99 mmol/L) and Group 2 (median 12.61 mmol/L). For the first time, AF lactate concentration was evaluated during parturition, and significantly higher levels were found in mares delivering healthy foals. This was an unexpected and very interesting result which warrants further investigation involving a larger number of mares. Additional studies are needed before either mare's blood or AF lactate concentration can be used in a clinical setting.

Association between lactate concentration in amniotic fluid and dysfunctional labor.

OBJECTIVES: To assess whether there is an association between high lactate concentration in amniotic fluid (AF) and labor dystocia. DESIGN: Prospective observational study. SETTING: Labor ward at General South Hospital, Stockholm, Sweden. POPULATION AND METHODS: Women in active labor attending labor ward, having at least two consecutive measurements of lactate concentration in AF, measured 60 minutes apart. MAIN OUTCOME MEASURE: Dysfunctional labor, defined as instrumental or operative delivery due to dystocia. RESULTS: Among women with spontaneous vaginal deliveries (n=23) the mean lactate concentration in AF during labor was 8.9 mmol/l (range 6.6-10.8), and among women with operative delivery due to labor dystocia (n=31) the corresponding value was 10.9 mmol/l (range 8.0-16.1) (p<0.001). Of 29 women with a high lactate concentration (> or =10.1 mmol/l) in at least two consecutive measures collected at least 60 minutes apart, 25 (86%) were delivered instrumentally/operatively due to dystocia. Using this definition of a positive test, the diagnostic accuracy to predict operative delivery due to dystocia was: sensitivity 81% (25/31), specificity 83% (19/23), positive predictive value 86% (25/29), and negative predictive value 76% (19/25). The likelihood ratio was 5.0 for a positive test and 0.2 for a negative test. CONCLUSIONS: High lactate concentration (> or =10.1mmol/l) in at least two consecutive samples of AF collected during labor 60 minutes apart is strongly associated with dystocia. This method might be useful in clinical management to identify labor dystocia at an early stage of labor.

Subclinical hypocalcaemia in captive Asian elephants (Elephas maximus).

The hypothesis that hypocalcaemia may play a role in dystocia in captive Asian elephants (Elephas maximus) was investigated. The objectives of the study were to measure the total calcium concentration in elephant plasma; assess the changes in parameters of calcium metabolism during a feeding trial; investigate a possible relationship between calcium metabolism and dystocia; and assess bone mineralisation in captive Asian elephants in vivo. The following parameters were measured: total and ionised calcium, inorganic phosphorous and magnesium, the fractional excretions of these minerals, intact parathyroid hormone, 25-OH-D(3) and 1,25-OH-D(3). Radiographs were taken from tail vertebrae for assessment of bone mineralisation. The mean (sd) heparinised plasma total calcium concentration was 2.7 (0.33) mmol/l (n=43) ranging from 0.84 to 3.08 mmol/l in 11 Asian elephants. There was no significant correlation between plasma total calcium concentration and age. Following feeding of a calcium rich ration to four captive Asian elephant cows, plasma total and ionised calcium peaked at 3.6 (0.24) mmol/l (range 3.4 to 3.9 mmol/l) and 1.25 (0.07) mmol/l (range 1.17 to 1.32 mmol/l), respectively. Plasma ionised calcium concentrations around parturition in four Asian elephant cows ranged from 0.37 to 1.1 mmol/l only. The present study indicates that captive Asian elephants might be hypocalcaemic, and that, in captive Asian elephants, the normal plasma concentration of total calcium should actually be around 3.6 mmol/l and normal plasma concentration of ionised calcium around 1.25 mmol/l. Given the fact that elephants absorb dietary calcium mainly from the intestine, it could be concluded that elephants should be fed calcium-rich diets at all times, and particularly around parturition. In addition, normal values for ionised calcium in captive Asian elephants should be reassessed.

Effects of dystocia, fetotomy and caesarian sections on the liver enzymes activities and concentrations of some serum biochemical parameters in dairy cattle.

The aim of the present study was to determine the level of serum liver enzymes, triglyceride and some metabolites in cows with or without difficulties during parturition. The second goal was to compare between the possible effects of caesarian section and fetotomy on these parameters. A total number of 24 native breed cows at full term were included in this study. Out of them, 8 gave normal parturition, 16 cows were admitted with dystocia. The group of dystocia was subdivided into two groups; fetotomy (n=8) and caesarian (n=8) group. In the caesarian group, 4 cows were with uterine torsion. Five blood samples were collected from each cow: directly pre-partum, during and just after delivery and at, 24, 48 and 72 h post-partum. Serum samples were used for determination of aspartate amino transferase (AST), glutamate dehydrogenase (GLDH), gamma glutamyl transferase (gamma-GT), creatine phosphokinase (CK), glucose, total bilirubin, cholesterol and triglyceride. The results showed that AST, GGT, GLDH and CK activities were significantly increased in the group with caesarian sections due to uterine torsion than the control and fetotomy groups. There were insignificant changes in serum GGT and GLDH activities between control, fetotomy and dystocia group without uterine torsion at pre-partum and at 24 and 48 h post-partum. At 72 h post-partum, there was a significant increase in GLDH activity without significant increase in serum GGT activity. The concentrations of cholesterol and triglycerides did not differ in cows with dystocia compared to normal cows. In conclusion, cattle subjected to caesarian section and especially those with uterine torsion are associated with hepatic dysfunction. On the other hand, fetotomy has no effect on hepatocellular damage. The type of parturition has no effect on the bilirubin, cholesterol and triglyceride concentrations just before parturition to the 3rd day post-partum. It is recommended to supply cows with liver supportive therapy after caesarian section with uterine torsion.

Relaxin physiology in the female reproductive tract during pregnancy.

The characteristic functions of relaxin are associated with female reproductive tract physiology. These include the regulation of biochemical processes involved in remodeling the extracellular matrix of the cervix and vagina during pregnancy and rupture of the fetal membranes at term. Such modifications enable the young to move unimpeded through the birth canal and prevent dystocia. However, relaxin's physiological actions are not limited to late gestation. New functions for this peptide hormone in implantation and placentation are also emerging. Relaxin promotes uterine and placental growth and influences vascular development and proliferation in the endometrium. This chapter provides an overview of the current literature on relaxin physiology in the uterus, cervix and vagina of pregnant females and the impact on fetal health. It also outlines the potential mechanisms of relaxin action, particularly in the cervical extracellular matrix and uterine endometrium.

Plasma hormones and metabolites in Piedmontese cows during late pregnancy: relationships with calf birth weight.

Relationships among plasma hormonal and metabolic variables in the last trimester of gestation in 59 Piedmontese dams (n = 15 heifers, n = 44 cows) and the calf birth weight (BWT) class of their offspring were investigated in seven herds. The BWT data were categorized as follows: > 50 kg (BWT-A), 46 to 50 kg (BWT-B), 41 to 45 kg (BWT-C), and < 41 kg (BWT-D). Blood samples were collected at 33, 36, and 39 wk of gestation. Packed cell volume (PCV) and plasma concentrations of insulin, estrone sulfate (E1SO4), NEFA, and creatinine were determined and correlated to BWT class. Creatinine: E1SO4 ratio also was calculated. Duration of gestation was greater for dams producing a BWT-A calf than for the other BWT classes, and calf BWT was heavier (P < 0.001) for calves in the BWT-A vs. BWT-D class. The heaviest calf in BWT-A was associated with the highest calving difficulty score. Insulin and PCV values were not affected by week of gestation, whereas plasma E1SO4, NEFA, and creatinine content increased (P < 0.001) and creatinine:E1SO4 decreased (P < 0.001) during late gestation. Calf BWT class did not affect PCV value. Plasma E1SO4 concentrations were lower (P < 0.01) in BWT-D dams than the other dams, showing the greatest difference at 39 wk of gestation. At 36 and 39 wk of gestation, dams bearing BWT-C and BWT-D calves had a higher (P < 0.01) plasma insulin concentration than those bearing BWT-A and BWT-B calves. Plasma NEFA concentrations at 39 wk of gestation were higher (P < 0.05) in dams of calf BWT-A than in the other dams. We conclude that plasma E1SO4 level is a variable that can be used to monitor problems related to a small size calf. Conversely, the forthcoming birth of a calf with a heavy BW seems to be preceded by a pronounced increase in plasma NEFA level in the dam just a few days before calving.

Endocrine changes in late bovine pregnancy with special emphasis on fetal well-being.

During late bovine pregnancy, several hormones are involved to maintain and develop a successful result with a live calf. These hormones are e.g., progesterone, high levels during the whole pregnancy period, originating from the corpus luteum, maternal adrenals and placenta. Oestrone sulphate, oestrone in its conjugated form, shows elevated levels from about mid-pregnancy until the third stage of parturition (expelling of the fetal membranes). For the onset of normal parturition and the parturition process as such, a change from progesterone to oestrone synthesis is crucial. The increasing levels of oestrone are time-related to an increased synthesis of prostaglandin F(2alpha) (reflected as elevated levels of 15-ketodihydro-PGF(2alpha)) causing prepartal luteolysis and several hormones are then involved in the labour process such as prostaglandin F(2alpha), cortisol and oxytocin. Cortisol might also be an indicator of stressful events for the dam. Levels of pregnancy associated glycoproteins (PAGs), originating from the trophoblastic binucleate cells, are increasing during the last 10 days prior to parturition. All the mentioned hormones have certain functions during pregnancy, more or less understood. However, could deviations from the expected profiles during late bovine pregnancy indicate impaired fetal well-being or be of importance for reproductive performance during the postpartum period? Abortions, stillbirths or dystocia are situations where endocrine profiles might predict the status of the calf. There are two possible approaches to study the endocrine changes in late pregnancy-to follow spontaneous cases of normal or impaired pregnancies or to experimentally disturb the gestation or induce parturition. We have in one study followed pregnant animals to depict reproductive disturbances, both animals with expected normal parturitions and animals where the sire of the calf has given rise to a high incidence of stillborn calves. The number of stillborn calves or dystocia has been small and so far it has not been possible to obtain a clear picture of the usefulness of endocrine parameters to follow fetal well being, but some of the hormonal parameters show a deviating profile. In a small group of animals with induced parturition (PGF(2alpha)), two out of three had parturition problems and one of these animals had a stillborn calf. All three animals had retained fetal membranes. It was possible to demonstrate a deviating endocrine profile in the cow having the stillborn calf in the sense of higher levels of progesterone, cortisol and 15-ketodihydro-PGF(2alpha) at the time of parturition. In both animals with dystocia the levels of oestrone sulphate after parturition were more sustained. Increasing and high levels of PAGs were only demonstrated in the animal with a normal parturition. These studies are ongoing, aiming at finding changes in endocrine profiles related to impaired pregnancies.

Relaxin deficiency in the placenta as possible cause of cervical dystocia. A case report.

In a case of cervical dystocia which had to be delivered by caesarean section, the placenta was examined for relaxin content. The placenta was processed by acidic acetone extraction and separation of the raw extract on a carboxymethylcellulose column. The activity of relaxin was estimated by means of heterologous porcine radioimmunoassay. The elution profile of the placenta extract showed significant differences to that of the placenta in normal deliveries i.e. there was no evidence of typical protein peaks with relaxin activity. It is suggested that there is possibly a causal relationship between the lack of placental relaxin and the pathological behaviour of the cervix during delivery.