Is similarity in Major Histocompatibility Complex (MHC) associated with the incidence of retained fetal membranes in draft mares? A cross-sectional study.

The failure of the maternal immune system to recognize fetal antigens and vice versa due to MHC similarity between the foal and its dam might result in the lack of placental separation during parturition in mares. The aim of the study was to investigate the influence of MHC similarity between a mare and a foal on the incidence of retained fetal membranes (RFM) in post-partum mares. DNA was sampled from 43 draft mares and their foals. Mares which failed to expel fetal membranes within three hours after foal expulsion were considered the RFM group (n = 14) and mares that expelled fetal membranes during the above period were the control group (n = 29). Nine MHC microsatellites of MHC I and MHC II were amplified for all mares and foals. MHC compatibility and MHC genetic similarity between mares and their foals was determined based on MHC microsatellites. The inbreeding coefficient was also calculated for all horses. The incidence of RFM in the studied population was 33%. Compatibility in MHC I and MHC II did not increase the risk of RFM in the studied population of draft mares (P>0.05). Differences in MHC similarity at the genetic level were not observed between mare-foal pairs in RFM and control group (P>0.05). We suspect that RFM in draft mares may not be associated with MHC similarity between a foal and its dam. Despite the above, draft horses could be genetically predisposed to the disease.

Review: Relationships between metabolism and neutrophil function in dairy cows in the peripartum period.

Aspects of neutrophil function are diminished or dysregulated in dairy cows in the weeks just before and after calving, which appears to be an important contributor to the occurrence of retained placenta, mastitis, metritis and endometritis. The timing and mechanisms by which specific elements of neutrophil function are impaired are only partially understood. Oxidative burst capacity is the element of neutrophil function most consistently shown to be impaired in the week after calving, but that observation may partially be biased because oxidative burst has been studied more than other functions. There is sufficient evidence to conclude that the availability of calcium and glucose, and exposure to elevated concentrations of non-esterified fatty acids or ß-hydroxybutyrate affect some aspects of neutrophil function. However, these factors have mostly been studied in isolation and their effects are not consistent. Social stressors such as a competitive environment for feeding or lying space should plausibly impair innate immune function, but when studied under controlled conditions such effects have generally not been produced. Similarly, treatment with recombinant bovine granulocyte colony-stimulating factor consistently produces large increases in circulating neutrophil count with modest improvements in function, but this does not consistently reduce the incidence of clinical diseases thought to be importantly attributable to impaired innate immunity. Research is now needed that considers the interactions among known and putative risk factors for impaired neutrophil function in dairy cows in the transition period.

The evaluation of superoxide dismutase activity, neutrophil function, and metabolic profile in cows with retained placenta.

The present study aimed to determine the alterations in pre- and postpartum immune function, superoxide dismutase (SOD) activity, and serum metabolite changes in Brown Swiss cows with or without retained placenta (RP). Peripheral blood was sampled at -10 ±â€¯4 days antepartum and 10 ±â€¯4 days postpartum for the assessment of neutrophil phagocytic and oxidative burst activities by using flow cytometry. SOD activity, beta hydroxybutiric acid (BHB), nonesterified fatty acids (NEFA), calcium (Ca), phosphorus, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), creatinine kinase (CK), gamma-glutamyl transferase (GGT), lactate dehydrogenase, bilirubin, cholesterol, glucose, urea, albumin, total protein, and triglyceride concentrations were also measured from serum samples collected at -10 ±â€¯4, 3 ±â€¯1, 10 ±â€¯4, and 30 ±â€¯4 days relative to parturition. All data were analyzed using the MIXED procedure of SPSS. Neutrophil phagocytic and oxidative burst activities, phagocytic and oxidative fluorescence intensity, and phagocytic and oxidative indexes were similar among the groups (P > 0.05). However, serum SOD activity was 30 ±â€¯4 IU/ml and 17 ±â€¯2 IU/mL for cows that subsequently developed RP and healthy cows at -10 ±â€¯4 days antepartum, respectively (P < 0.05). Body condition scores were similar in both groups (P > 0.05). All investigated serum metabolic parameters varied significantly over time (P < 0.001). Cows affected with RP had subclinical hypocalcemia (8.06 ±â€¯0.3 mg/dl) and had significantly higher BHB levels (1027 ±â€¯137.9 mmoL/l) at 3 ±â€¯1 days postpartum. Furthermore, these cows had greater AST and NEFA concentrations around calving (P < 0.05). In conclusion, retained placenta had no prolonged effect on the measures of neutrophil function during the postpartum period. On the other hand, increased antepartum SOD activity might be a predisposing factor and can be used as a predictive biomarker for retained placenta.

Impact of uterine macrophage phenotype on placental retention in dairy cows.

Reproductive diseases affect 25% of dairy cows in the US and often develop from retention of the placenta. It is well established that expulsion of the placenta is a highly regulated inflammatory process, but the mechanisms by which dysregulation of uterine immune responses impair this process are poorly understood. In healthy non-ruminants, pro-inflammatory M1 macrophages are predominant in uterine tissue after parturition. However, macrophage phenotype in the postpartum bovine uterus is unknown. Our study compared macrophage phenotypes in the uterine caruncles of multiparous dairy cows that during the first day postpartum either retained (RET, n = 5) or had normal expulsion (NOR, n = 5) of placenta. Immune cells were sorted magnetically from the caruncular endometrial cell fraction using the CD172a marker and monocyte/macrophage population was characterized using flow cytometry. Transcriptional and protein expression studies were performed on uterine caruncles. Compared to NOR, RET samples showed a lower CD14+/CD16+ expression (P < 0.05) in caruncle monocyte/macrophage population. As opposed to NOR, RET further demonstrated greater expression of anti-inflammatory M2 macrophage associated genes CD206, C-type lectin domain family 7 member A (CLEC7A), and RNASE6. In addition, caruncles from RET showed decreased signal transducer and activator of transcription 3 (STAT3) activation, an important promoter of proteolytic activity, compared to NOR. Our studies demonstrate that there is an overall lower number of macrophage populations in the caruncle of cows with RET placenta and these are polarized towards M2 phenotype. Excessive accumulation of M2 macrophages may lead to reduced trafficking of immune cells into the caruncle thus impairing the inflammatory, phagocytic and proteolytic processes that lead to placental expulsion.

Depressed polymorphonuclear cell functions in periparturient cows that develop postpartum reproductive diseases.

The study was planned to see if there is any important and significant changes in the PMN function in cows suffering from postpartum reproductive diseases (PRD). Blood sampling was done from 41 pregnant cows on 15 days prepartum (-15d), calving day (0d), 15 days (15d) and 30 days (30d) postpartum and thorough gynaecological examination was performed on 0d, 15d, 30d and 45d for diagnosis of PRD like retained placenta (RP), clinical metritis (CM), clinical endometritis (CE) and delayed involution of uterus (DIU). The heparinised blood was used for isolation of PMN leukocytes for estimation of superoxide (SO), hydrogen peroxide (H2O2) and enzyme myeloperoxidase (MPO) activity in each group of cows. The SO production (ΔOD) was greater for normal (0.19 ± 0.05) than cows suffering from RP (-0.12 ± 0.09), CM (-0.15 ± 0.13) and CE (-0.07 ± 0.05) at -15d. The mean value was greater for normal cows (0.12) than the cows with PRD (0.05 to 0.9) at 30d. The H2O2 production was greater for normal than cows with PRD at all sampling days and significantly greater than cows with RP and CE at 15d (p < 0.01) and 30d (P < 0.05). The MPO activity (µmol/1 × 107) was greater for normal (18.77 ± 1.27) than for RP (12.52 ± 2.57) and CM (11.31 ± 3.30) cows on 0d. The depressed capability of the PMN from the cows with PRD to produce SO, H2O2 and MPO during the periparturient period indicated their association with the development of RP, CM and CE.

Nutritional strategies to optimize dairy cattle immunity.

Dairy cattle are susceptible to increased incidence and severity of both metabolic and infectious diseases during the periparturient period. A major contributing factor to increased health disorders is alterations in bovine immune mechanisms. Indeed, uncontrolled inflammation is a major contributing factor and a common link among several economically important infectious and metabolic diseases including mastitis, retained placenta, metritis, displaced abomasum, and ketosis. The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. There is now a greater appreciation that certain mediators of the immune system can have a reciprocal effect on the metabolism of nutrients. Thus, any disturbances in nutritional or immunological homeostasis can provide deleterious feedback loops that can further enhance health disorders, increase production losses, and decrease the availability of safe and nutritious dairy foods for a growing global population. This review will discuss the complex interactions between nutrient metabolism and immune functions in periparturient dairy cattle. Details of how either deficiencies or overexposure to macro- and micronutrients can contribute to immune dysfunction and the subsequent development of health disorders will be presented. Specifically, the ways in which altered nutrient metabolism and oxidative stress can interact to compromise the immune system in transition cows will be discussed. A better understanding of the linkages between nutrition and immunity may facilitate the design of nutritional regimens that will reduce disease susceptibility in early lactation cows.

Periparturient stress and immune suppression as a potential cause of retained placenta in highly productive dairy cows: examples of prevention.

The immune system during the periparturient period is impaired. At this time the most important factor causing immune-suppression in highly productive cows is metabolic stress resulting from hormonal and metabolic fluctuations, a negative energy balance, shortage of proteins, minerals and vitamins which are required to meet the demands of the fetus as well as the onset of lactation. This stress can activate the hypothalamic-pituitary-adrenocortical axis (HPA), which results in increase plasma corticosteroids. As a result, the cortisol concentration during the periparturient period increases by several folds particularly on the day of calving. Cortisol is a powerful immune-suppressive agent. During stress, this hormone causes depression of the leukocyte proliferation and their functions. Decreased phagocytosis of neutrophils, decreased cytotoxic ability of lymphocytes, as well as depressed activity of their cytokines, make it impossible for the normal, efficient maternal immune recognition and rejection of fetal membranes (as a foreign, allogeneic tissue expressed fetal antigens-MHC class I proteins by trophoblast cells) and finally results in their retention in cows. The metabolic periparturient stress also activates production of catecholamines, especially adrenalin. Adrenalin activates adrenoreceptors of the myometrium and then causes hypotony or atony of the uterus. Thus, cortisol and adrenalin inhibit rejection and expulsion of fetal membranes and cause their retention. These mechanisms of retained placenta (RP) often have a metabolic etiology and occur in herds, where important infectious diseases causing placentitis are absent or prevented. The aim of this article is to show the fundamental mechanisms occurring during periparturient stress and the accompanied immune-suppression in cows, as well as their consequences in relation to RP. The paper also gives examples of the symptomatic prevention of RP in cows caused by metabolic and immune suppressive factors. The prevention of RP was carried out using drugs which inhibit the activity of cortisol or adrenalin in dairy cows during calving.

Short communication: Association of disease incidence and adaptive immune response in Holstein dairy cows.

The objective of this study was to use previously calculated estimated breeding values for cell- (CMIR) and antibody-mediated immune responses (AMIR) to determine associations between immune response (IR) and economically important diseases of dairy cattle. In total, 699 Holsteins were classified as high, average, or low for CMIR, AMIR, and overall IR (combined CMIR and AMIR), and associations with mastitis, metritis, ketosis, displaced abomasums, and retained fetal membranes were determined. The incidence of mastitis was higher among average cows as compared with cows classified as high AMIR [odds ratio (OR)=2.5], high CMIR (OR=1.8), or high IR (OR=1.8). Low-CMIR cows had a higher incidence of metritis (OR=11.3) and low-IR cows had a higher incidence of displaced abomasum (OR=4.1) and retained fetal membrane (OR=2.8) than did average responders. Results of this study show that cows classified as high immune responders have lower occurrence of disease, suggesting that breeding cattle for enhanced IR may be a feasible approach to decrease the incidence of infectious and metabolic diseases in the dairy industry.

Two-way calf to dam major histocompatibility class I compatibility increases risk for retained placenta in cattle.

PROBLEM: In cattle, retained placenta (RP) is suggested to arise from failure of immune-mediated rejection of the fetal membranes by the maternal immune system and is associated with major histocompatibility (MHC) class I compatibility between calf and dam. METHOD OF STUDY: To study the association between RP and different MHC class I compatibilities between calf-dam-granddam combinations, massively parallel pyrosequencing was used to determine the MHC class I haplotypes of cows with and without RP. RESULTS: Two-way calf to dam MHC class I compatibility gave a high risk for RP. There was a tendency for a higher risk for RP with calf to dam MHC class I compatibility. CONCLUSIONS: We concluded that in two-way compatible pregnancies, the maternal immune system fails to reject the fetal membranes, and the fetal immune system does not mount an immune response against maternal MHC class I antigens that could influence the immune-mediated rejection of the fetal membranes by the maternal immune system. The lack of immune-mediated rejection of the fetal membranes by the maternal immune system increases the risk of occurrence of RP.

Chemotactic activity of cotyledons for mononuclear leukocytes related to occurrence of retained placenta in dexamethasone induced parturition in cattle.

Induction of parturition with glucocorticosteroids in cattle is used for research purposes, in diseased or injured pregnant cows, and as a management tool to time parturition. A negative side effect of induction of parturition with glucocorticosteroids is the high incidence of retained placenta that occurs after these calvings. Reaction of the maternal immune system against the 'foreign' foetal membranes contributes to the breakdown of the foetal-maternal attachment. Several studies indicate that failure of this immune assisted detachment increases the occurrence of retained placenta. We hypothesized that retained placenta occurring after induction of parturition with glucocorticosteroids is caused by failure of immune assisted detachment of the foetal membranes. The chemotactic activity of cotyledons for mononuclear leukocytes was used as a parameter to see whether immune assisted detachment of the foetal membranes had occurred. Cotyledons were collected from spontaneously calving non-retained placenta cows and from dexamethasone induced non-retained placenta and retained placenta cows. The study showed that the chemotactic activity of cotyledons for mononuclear leukocytes was lower (P < 0.001) in cotyledons obtained from retained placenta cows in which parturition was induced with dexamethasone compared to the chemotactic activity of cotyledons obtained from spontaneously calving non-retained placenta cows, whereas the chemotactic activity of cotyledons obtained from induced non-retained placenta cows was not lower (P = 0.10) than the chemotactic activity of cotyledons obtained from spontaneously calving non-retained placenta cows. We concluded that induction of parturition with dexamethasone causes a failure of immune assisted detachment of the foetal membranes and the accompanying release of chemotactic factors. As a result, the chemotactic activity of cotyledons for mononuclear leukocytes is lower in induced retained placenta cows than in cotyledons from non-retained placenta cows in which successful immune assisted detachment of the foetal membranes occurs.

Natural killer cells and HLA-G expression in the basal decidua of human placenta adhesiva.

Retained placenta is caused by abnormal adherence of the placenta to the uterine wall, leading to delayed expulsion of the placenta and causing postpartum haemorrhage. The mildest form of retained placenta is the placenta adhesiva (PA), of which the cause is unknown. The aim of our study was to explore possible differences in immune response in the basal decidua between PA and control placentas (CP). We performed a descriptive analysis of immunohistochemical differences in 17 PA and 10 CP. Our results show that in PA the amount of uterine natural killer (uNK) cells is significantly reduced (0.2 uNK cell/standardised area) as compared to CP (9.8 uNK cell/standardised area, p < 0.001) whereas the number of trophoblast cells and the expression of HLA-G by trophoblast are similar in the decidua of PA and CP. We speculate that adequate numbers of uNK cells in the basal decidua are needed for normal expulsion of the placenta.

Bacteriological and cytological findings during the late puerperal period after two different treatments of retained placenta followed by acute puerperal metritis.

The aim of the study was to compare the effect of two acute puerperal metritis (APM) treatment protocols on uterine condition during the late puerperal period (5th to 7th week). Late gestation healthy cows (n = 21) were divided randomly in three equal groups. Parturitions were induced. Treatments of APM were started on the third day postpartum (PP). Group A was treated with an oxytocin analogue carbetocin for three days and intrauterine administration of cephapirin between days 15 and 17. Group B was given intramuscular injection of ceftiofur for five days followed by two injections of prostaglandin F2alpha, at an interval of 12 h, on the eighth day PP. Group C served as the control group with no treatment. Body temperature was recorded daily for 14 days PP. Uterine biopsies for bacteriology, and uterobrush samples for cytology, were taken once a week from the 5th to 7th week postpartum. No differences were found in body temperature on day 14 PP, presence of bacteriological infections and disappearance of uterine inflammatory signs diagnosed by cytological examination between experimental groups.

Structure and function of the bovine fetomaternal unit in relation to the causes of retained fetal membranes.

Approximately 5 per cent of dairy cows are affected by retained fetal membranes. Retained fetal membranes are an important risk factor for the metritis/endometritis disease complex occurring in early lactation, and costs the UK dairy industry approximately pound16 million annually in lost production. Veterinary clinicians have described the clinical signs, treatment and some associated risk factors of the condition since early Victorian times, and these have not changed over time. Research carried out within the past 20 years suggests that there is an immunological basis for retained fetal membranes. In a normal calving, the maturation of the placenta and its separation from healthy caruncles depends upon incompatibility between maternal and fetal major histocompatibility complex class I expressed on epithelium within the fetomaternal unit. Placental maturation follows stimulation of the maternal immune response and the production of neutrophil-activating factors within the epithelium in the caruncular arcade. This affects the extracellular matrix components within the placentome, breaking down collagen within the chorionic villi and assisting in separation from the caruncle. Factors influencing normal placental maturation include downregulation of antioxidative defence mechanisms against reactive oxygen species, a lower ratio of prostaglandin E(2) to prostaglandin F(2alpha) within the fetomaternal compartments of the placentome, and an elevated steroid hormone receptor status, which reduces the rate of apoptosis occurring in the chorionic epithelium before calving.

RCAS1 decidual immunoreactivity during placental abruption: immune cell presence and activity.

PROBLEM: RCAS1 is a protein responsible for the suppression of cytotoxic immune response during gestation. The present study evaluates the immunoreactivity level of RCAS1 with respect to immune cell status during placental abruption (PA) and retained placental tissue (RPT). METHOD OF STUDY: RCAS1, CD3, CD56, CD69 and CD25 immunoreactivity was assessed by immunohistochemistry in 66 decidual samples derived from PA and from RPT. RESULTS: RCAS1 immunoreactivity was statistically significantly higher in decidual tissue samples derived from patients with RPT than in those derived from patients with PA. A statistically significantly lower number of CD56(+) and CD3(+) cells and immunoreactivity level of CD69 were found in patients with RPT, compared to those with PA. CONCLUSION: Placental abruption seems to be associated with excessive accumulation and activity of CD3(+) and CD56(+) cells in decidua, which processes might, in turn, result from an insufficient RCAS1 decidual level.

The molecular changes during placental detachment.

OBJECTIVES: RCAS1 is a membrane protein that plays a role in the maintenance of maternal immune tolerance during pregnancy. The work presented here demonstrates the results of RCAS1 expression in placenta in cases of placental abruption and patients with retained placental tissue during the third stage of labor. STUDY DESIGN: The placenta tissue samples were obtained during vaginal and cesarean delivery (derived from 117 pregnancies). Pregnant women were divided into four groups according to the onset of labor and the time of placental detachment in term labors. The samples were analyzed by the Western blot method. Statistical analysis was performed using the Shapiro-Wilk procedure. The Mann-Whitney test and Student's t-test were applied to compare the differences between parametric data. RESULTS: The average relative amount of RCAS1 observed in those patients with retained placental tissue was statistically significantly higher than in the patients with placental abruption. CONCLUSION: The differences observed in placental RCAS1 levels confirm the participation of this protein in the inhibition of maternal immune response during gestation. The present results also indicate that RCAS1 participates in the changes in the maternal immune system that take place during parturition and reinforce its potential involvement in the mechanism of placental abruption.

Major histocompatibility antigen expression on the bovine placenta: its relationship to abnormal pregnancies and retained placenta.

In viviparous animals, regulation of expression of major histocompatibility complex (MHC) class I antigens by the trophoblast cells, which constitute the outermost layer of the placenta, seems to be critical for maternal immunological acceptance of an allogeneic fetus. Cattle are unusual in this regard, since the bovine trophoblast cells, in specific regions of the uterine/placental interface, normally express MHC class I antigens during the third trimester of gestation. This expression appears to be biologically relevant as MHC class I compatibility between a cow and her fetus has been associated with an increased incidence of placental retention. We have found significant differences in lymphocyte populations, cytokine production, and trophoblast cell apoptosis in the placentomes of MHC-compatible and -incompatible pregnancies at parturition. This suggests that maternal immunological recognition of fetal MHC class I proteins triggers an immune/inflammatory response that contributes to placental separation at parturition in cattle. Early in pregnancy, a complete shutdown of MHC class I expression by trophoblast cells appears to be critical for normal placental development and fetal survival. In bovine somatic cell nuclear transfer (SCNT) pregnancies, there is an extremely high rate of fetal loss between days 30 and 90 of pregnancy. We have shown that in bovine SCNT pregnancies, between days 34 and 63 of gestation, there is both abnormal expression of MHC class I antigens by trophoblast cells and an abnormal accumulation of lymphocytes within the uterine stroma. Consequently, it is likely that activation of the maternal mucosal immune system, within the uterus at the same time when placentomes are being established, interferes with the process of placentome development and leads to immune-mediated abortion. Our data suggest that bovine MHC-compatible pregnancies provide a unique model for studying regulation of the uterine immune system, as well as immune-mediated placental rejection.

Decreased neutrophil function as a cause of retained placenta in dairy cattle.

It is unclear why some cows fail to expel the placenta following calving. One theory suggests the fetal placenta must be recognized as "foreign" tissue and rejected by the immune system after parturition to cause expulsion of the placenta. We hypothesized that impaired neutrophil function causes retained placenta (RP). We examined the ability of neutrophils to recognize fetal cotyledon tissue as assessed by a chemotaxis assay, which utilized a placental homogenate obtained from a spontaneously expelled placenta as the chemoattractant. Neutrophil killing ability was also estimated by determining myeloperoxidase activity in isolated neutrophils. Blood samples were obtained from 142 periparturient dairy cattle in two herds. Twenty cattle developed RP (14.1%). Neutrophils isolated from blood of cows with RP had significantly lower neutrophil function in both assays before calving, and this impaired function lasted for 1 to 2 wk after parturition. The addition of antibody directed against interleukin-8 (IL-8) to the cotyledon preparation used as a chemoattractant inhibited chemotaxis by 41%, suggesting that one of the chemoattractants present in the cotyledon at parturition is IL-8. At calving, plasma IL-8 concentration was lower in RP cows (51 +/- 12 pg/ml) than in cows expelling the placenta normally (134 +/- 11 pg/ml). From these data, we suggest that neutrophil function is a determining factor for the development of RP in dairy cattle. Also, depressed production of IL-8 may be a factor affecting neutrophil function in cows developing RP.

Reduced phagocytotic activity of macrophages in the bovine retained placenta.

This study was carried out to investigate the distribution of immune cells in the bovine placenta during the postpartum period and to compare these cells between normal and retained placenta. Within 1 h after normal calving, biopsy samples of placentomes were collected from 10 cows. The occurrence of retention of fetal membranes was monitored for more than 8 h post-calving, and the samples obtained were divided into two groups: normally discharged and retained placenta (n = 5 each). Immunohistochemical procedures were utilized to detect macrophages and T lymphocytes. Numerous CD14-positive macrophages were found in the stroma of both normal placenta and retained placenta whereas only a few CD3-positive T lymphocytes were found in both cases. However, histochemical staining for acid phosphatase, a predominant lysozomal enzyme, revealed that almost all macrophages showed strong enzyme activity in the normally discharged placentas, whereas in retained placenta the activity of acid phosphatase was conspicuously decreased in intensity. These results indicate that there are functional differences in placental macrophages between normal and retained placenta.

[Effect of progesterone on the immune system in consideration of bovine placental retention]. / Einfluss von Progesteron auf das Immunsystem mit Berücksichtigung der bovinen Retentio secundinarum.

Effects of progesterone on the immune system of different species are presented by a literature study. Elevated progesterone concentrations in blood result in more severe course and longer persistence of bacteria in infectious diseases and decrease of the clearance of antibody-coated erythrocytes in vivo. Progesterone suppresses specific components of the immune system and natural killer (NK) cell activity while it has a mainly positive influence on other nonspecific components. It suppresses blastogenesis and cytotoxicity of lymphocytes and increases synthesis of asymmetric antibodies without effector function to block fetal antigens. Progesterone increases the concentration of leucocytes in blood, random migration and chemotactic ability, synthesis of reactive oxygen intermediates (ROI) and antibody-dependent cellular cytotoxicity of polymorphonuclear leucocytes (PMN) and expression of complement receptors, synthesis of ROI and phagocytosis of peritoneal macrophages. In the uterus mainly immunosuppressive effects of progesterone are described (decreased migration of PMN into the gravid uterus, persistence of bacteria or transplants, synthesis of immunosuppressive uterine milk proteins, decreased random migration of PMN) except for an increased content of IgA in the secretory products indicating a significance of progesterone in the pathogenesis of endometritis mainly in the cow and bitch. No correlation could be found between blood concentrations of progesterone and placental retention in cattle. Progesterone takes part in avoiding immunologic aggression of the maternal organism against the semiallogenic conceptus by suppressing specific components of the immune system and NK cell activity. Positive effects on nonspecific components of the immune system could be regarded as compensatory mechanisms to maintain the efficiency of the complete immune system.

[Effect of estrogens on the immune system with regard to bovine placental retention]. / Einfluss von Ostrogenen auf das Immunsystem mit Berücksichtigung der bovinen Retentio secundinarum.

A survey of effects of estrogens on the immune system is given by a literature study. Changes in number and functionality of single populations of cells of the immune system are shown. Results often vary in dependence on the examined parameters, on the type of the used or measured estrogens, on the measuring methods and between the different species. Independent from that the capacity of the nonspecific cellular immune system seems to be increased under the influence of estrogens. Individuals with high estrogen levels showed an increase of the number of leucocytes and neutrophil granulocytes in the blood. In most of the functional studies on neutrophil granulocytes a suppressive effect of estrogens independent from the species could only be observed on the ability of directed migration. A stimulation or no effects of estrogens were reported on all the other parameters (random migration, phagocytosis, generation of reactive oxygen metabolites, cytotoxicity). Less is known about the effects of estrogens on mononuclear cells (lymphocytes, monocytes, natural killer cells). Mainly lymphocytes showed a decrease in their number in the blood and a suppressive effect of isolated cells in different species. It remains for further studies whether estrogens are of significance for bovine retained placenta by having effects on components of the immune system, and how significant they are.