Pentraxin-3, endothelin-1, some biochemical parameters and hematology in bovine respiratory disease complex.

Abstract. Background: Infectious bovine respiratory disease complex (BRDC) is one of the world's major livestock problems. Aims: The study aimed to determine the diagnostic importance of pentraxin-3, endothelin-1, clinical biochemistry, and hematological parameters in infectious BRDC. Methods: Animals in this study were Simmental breed, 1-7 years old, untreated, and healthy and BRDC cattle (40 cattle with BRDC in the disease group, and 10 healthy cattle in the control group). Clinical findings such as general posture, respiratory rate per minute, rectal temperature, heart rate per minute, and mental posture of the diseased cattle were recorded. Blood samples were taken from the jugular vein only once from all cattle. Complete blood count from blood samples was measured in an automatic complete blood count device, biochemical parameters in an autoanalyzer, and pentraxin-3 and endothelin-1 were measured by ELISA method. Results: Rectal temperature, respiratory and pulse rates per minute, total leukocyte count, gamma-glutamyl transferase, urea, total bilirubin, lactate dehydrogenase, creatine kinase, pentraxin-3 and endothelin-1 concentrations were found to be statistically higher in BRDC group than those in the control group (P<0.001). Conclusion: Pentraxin-3 and endothelin-1 levels were statistically significantly higher in the BRDC group compared to the control group. As a result, pentraxin-3 and endothelin-1 were found to be diagnostically important in cattle diagnosed with BRDC.

Live birth rate from euploid blastocysts is not associated with infertility etiology or oocyte source following frozen-thawed embryo transfer (FET): analysis of 4148 cycles reported to SART CORS.

PURPOSE: To investigate whether live birth rates from euploid blastocyst frozen-thawed embryo transfer (FET) cycles are associated with infertility diagnosis or oocyte source. DESIGN: Retrospective analysis of FET cycles reported to SART CORS in 2014. METHODS: Data from fresh IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A), linked to the first FET cycles, were collected from the 2014 SART CORS database for autologous and donor oocyte cycles. Inclusion criteria were patients undergoing FET with euploid embryos (n = 4148). Demographic data including age, BMI, prior fertility, and etiology of infertility were collected from the retrieval cycle and analyzed. Patients with uterine anomalies, preimplantation genetic testing-mutation (PGT-M) for genetic diseases, gender selection, HLA determination, or systemic and immunologic disorders were excluded. The primary outcome measure was live birth (LB) rate. Potential confounders such as age, prior fertility, and maximum baseline FSH values were analyzed with regression models as indicated. RESULTS: Though age, maximum baseline FSH, and infertility diagnosis were significantly different, LB was similar between patients undergoing autologous or donor oocyte FET cycles. Etiology of infertility was not significantly associated with LB in autologous cycles (p = 0.95). Potential confounders such as maternal age, prior fertility, and maximum baseline FSH were not associated with outcomes; however, maternal BMI was inversely related to LB in autologous cycles, with an odds ratio of 0.97 (95% CI: 0.96-0.98 (rho = - 0.08, p < 0.01)). CONCLUSIONS: After controlling for confounding variables, a euploid embryo derived from a donor or autologous oocyte results in similar LB in women with different infertility diagnoses.

Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D.

STUDY QUESTION: Does vitamin D attenuate the adverse effects of advanced glycation end products (AGEs) on steroidogenesis by human granulosa cells (GCs)? SUMMARY ANSWER: AGEs alter the expression of genes important in steroidogenesis while 1,25-dihydroxyvitamin D3 (vit D3) in vitro attenuates some of the actions of AGEs on steroidogenic gene expression, possibly by downregulating the expression of the pro-inflammatory cell membrane receptor for AGEs (RAGE). WHAT IS KNOWN ALREADY: Vitamin D attenuates the pro-inflammatory effects of AGEs in non-ovarian tissues. STUDY DESIGN, SIZE, DURATION: Women who were undergoing IVF were enrolled. Follicular fluid samples (n = 71) were collected and cumulus GCs (n = 12) were treated in culture. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid levels of the anti-inflammatory soluble RAGE (sRAGE), AGEs and 25-hydroxyvitamin D (25-OHD) were quantified for possible correlations. GCs of each participant were split equally and treated with either media alone (control) or with human glycated albumin (HGA as a precursor for AGEs) with or without vit D3 after which RT-PCR and immunofluorescence were performed and cell culture media estradiol (E2) levels were compared. MAIN RESULTS AND THE ROLE OF CHANCE: In follicular fluid, sRAGE levels were positively correlated with 25-OHD levels. HGA treatment (i) increased CYP11A1 (by 48%), 3ß-HSD (by 38%), StAR (by 42%), CYP17A1 (by 30%) and LHR (by 37%) mRNA expression levels (P < 0.05 for all) but did not alter CYP19A1 or FSHR mRNA expression levels; and (ii) increased E2 release in cell culture media (P = 0.02). Vit D3 treatment (i) downregulated RAGE mRNA expression by 33% and RAGE protein levels by 44% (P < 0.05); (ii) inhibited the HGA-induced increase in CYP11A1, StAR, CYP17A1 and LHR mRNA levels, but not the increase in 3ß-HSD mRNA levels; and (iii) did not inhibit the HGA-induced E2 release in cell culture media. LIMITATIONS REASONS FOR CAUTION: This study used luteinized GCs that were collected from women who received gonadotropins thus the results obtained may not fully extrapolate to non-luteinized GCs in vivo. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that there is a relationship between AGEs and their receptors (RAGE and sRAGE) with vitamin D. Understanding the interaction between AGEs and vitamin D in ovarian physiology could lead to a more targeted therapy for the treatment of ovarian dysfunction. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from NIH (R01 NS045940), American Society for Reproductive Medicine, Ferring Pharmaceuticals Inc., and University of Vermont College of Medicine Bridge Funds. All authors have nothing to disclose.

Role of advanced glycation end-products in obesity-related ovarian dysfunction.

Obesity affects ovarian function, one of the main regulators of female fertility. Tissue levels of the proinflammatory advanced glycation end-products (AGEs) and their receptors (RAGE) are elevated in obesity. AGEs are key contributors to perturbations in the ovarian microenvironment. On this basis, the present review focuses on clinical and experimental studies supporting the role of AGE-RAGE system as a contributor to obesity-related ovarian dysfunction. Particular emphasis has been given to changes in AGEs, RAGE and the anti-inflammatory soluble receptor (sRAGE) levels in obesity state and following dietary interventions (high-fat diet and weight loss). Ovarian sensitivity, in particular granulosa cell function and oocyte meiosis, to the pro-inflammatory AGE-RAGE system as well as the relationship of follicular fluid AGEs and sRAGE to in vitro fertilization outcome are also discussed. Overall, obesity, with its alterations in the AGE-RAGE system, can disrupt the ovarian microenvironment potentially compromising oocyte competence and fertility. This review underscores a critical need to uncover the mechanistic actions of AGE-RAGE system in obesity-related ovarian dysfunction. Clinical and basic studies focusing on elucidating the patterns of accumulation and role of the AGE-RAGE system in human ovarian follicles are key steps in understanding their contribution to the health of human oocytes and embryos.

Anxiety- and depression-like behavior are correlated with leptin and leptin receptor expression in prefrontal cortex of streptozotocin-induced diabetic rats.

Anxiety and depression are common in diabetics. Diabetes also may cause reduced leptin levels in the blood. We investigated the relation between diabetes induced anxiety- and depression-like behavior, and leptin and leptin receptor expression levels in diabetic rats. The anxiety- and depression-like behaviors of rats were assessed 4 weeks after intraperitoneal injection of streptozotocin. Diabetic rats exhibited greater anxiety-like behavior; they spent more time in closed branches of the elevated plus maze test and less time in the center cells of the open field arena. Increased depression-like behavior was observed in diabetic rats using the Porsolt swim test. Prefrontal cortex (PFC), blood leptin levels and PFC neuron numbers were decreased, and leptin receptor expression and apoptosis were increased in diabetic rats. Blood corticosterone levels also were increased in diabetic rats. These results indicate that reduction of leptin up-regulates leptin receptor expression and may affect PFC neurons, which eventually triggers anxiety- and depression-like behaviors in diabetic rats.

Effects of exercise and poor indoor air quality on learning, memory and blood IGF-1 in adolescent mice.

It is known that regular aerobic exercise enhances cognitive functions and increases blood insulin-like growth factor 1 (IGF-1) levels. People living in urban areas spend most of their time indoors and indoor air quality can affect health. We investigated the effects of aerobic exercise in poor and good air quality environments on hippocampus and prefrontal cortex (PFC) neurons, anxiety, and spatial learning and memory in adolescent mice. Poor air quality impaired spatial learning and memory; exercise did not affect learning or memory impairment. Exercise in a good air quality environment improved spatial learning and memory. Poor air quality increased apoptosis in the hippocampus and PFC. Both exercised and sedentary groups living in a poor air quality environment had lower serum IGF-1 levels than those living in a good air quality environment. Living in a poor air quality environment has negative effects on the hippocampus, PFC and blood IGF-1 levels in adolescent mice, but exercise did not alter the negative effects of poor air quality.

Progesterone treatment decreases traumatic brain injury induced anxiety and is correlated with increased serum IGF-1 levels; prefrontal cortex, amygdala, hippocampus neuron density; and reduced serum corticosterone levels in immature rats.

Traumatic brain injury (TBI) may cause neuropsychiatric problems, such as anxiety disorder, that have negative effects on cognitive functions and behavior. We investigated the effects of progesterone on traumatic brain injury induced anxiety in 7-day-old rat pups subjected to contusion injury. Progesterone treatment decreased TBI induced anxiety and serum corticosterone levels, and increased serum IGF-1 levels. Moreover, progesterone treatment increased amygdala, prefrontal cortex and hippocampal neuron density. We found a negative correlation between serum corticosterone levels and anxiety tests, and a positive correlation between serum IGF-1 levels and anxiety tests. In addition, progesterone treatment decreased serum corticosterone compared to the controls and sham. Our results indicate that single dose progesterone may be effective for treating anxiety caused by TBI.

Leptin suppresses anti-Mullerian hormone gene expression through the JAK2/STAT3 pathway in luteinized granulosa cells of women undergoing IVF.

STUDY QUESTION: Do the adipocytokines, leptin and adiponectin affect the granulosa cell expression of anti-Mullerian hormone (AMH) and its receptor (AMHR-II)? SUMMARY ANSWER: Leptin suppresses AMH mRNA levels in human luteinized granulosa cells through the JAK2/STAT3 pathway, while adiponectin has no such effect. WHAT IS KNOWN ALREADY: AMH is one of the most reliable markers of ovarian reserve. Serum AMH levels decline with obesity. Obesity is associated with elevated leptin and reduced adiponectin levels. STUDY DESIGN, SIZE AND DURATION: This prospective study included 60 infertile women undergoing fresh IVF and ICSI cycles utilizing autologous oocytes at Montefiore's Institute for Reproductive Medicine and Health between July 2010 and April 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid was collected from small (SFs; <14 mm) and large follicles (LFs; ≥14 mm) from 38 participants. Total RNA was extracted separately from mural and cumulus granulosa cells and mRNA levels were measured by RT-PCR. In an additional group of participants (N = 22), primary cumulus and mural granulosa cells (pooled SFs and LFs) were cultured in media alone or with addition of either leptin (N = 7), adiponectin (N = 8) or JAK2/STAT3 inhibitor + leptin (N = 7), and AMH and AMHR-II mRNA levels measured. Levels of AMH, leptin and adiponectin protein were measured in follicular fluid. MAIN RESULTS AND THE ROLE OF CHANCE: AMH and AMHR-II mRNA and follicular fluid AMH protein levels were inversely correlated with age. AMH mRNA expression was six times higher in cumulus compared with mural granulosa cells in SFs (P< 0.05) and eight times higher in cumulus compared with mural granulosa cells in LFs (P < 0.001). In follicular fluid, leptin protein level positively correlated (r = 0.7, P = 0.03), while adiponectin protein level inversely correlated (r = -0.46, P = 0.02) with BMI. Leptin treatment suppressed AMH and AMHR-II mRNA in both cumulus and mural granulosa cells (all P < 0.05). In the presence of JAK2/STAT3 inhibitor, leptin treatment did not alter AMH but continued to suppress AMHR-II mRNA in cumulus cells (P = 0.02). Adiponectin treatment did not alter AMH or AMHR-II mRNA levels. LIMITATIONS, REASONS FOR CAUTION: This study included a luteinized granulosa cell model as these cells were collected from women who were hyperstimulated with gonadotrophins. The results obtained may not fully extrapolate to non-luteinized granulosa cells. WIDER IMPLICATIONS OF THE FINDINGS: Leptin may program abnormal AMH signaling, thereby resulting in ovarian dysfunction. This study opens a new perspective for understanding the low ovarian reserve seen in obese women and provides new insights into potential mechanisms that explain the lower AMH seen in obese women. Whether our findings explain the worse response to ovulation induction observed in obese women needs to be further elucidated.

In vitro maturation improves oocyte or embryo cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation.

This study tested in-vitro maturation (IVM) as a complementary strategy to improve the mature oocyte yield of breast cancer patients undergoing ovarian stimulation for fertility preservation. Secondary analysis of prospectively collected data is performed for 32 breast cancer patients undergoing oocyte or embryo cryopreservation before chemotherapy. Total number of oocytes and/or embryos cryopreserved following IVM is compared with the total number cryopreserved before IVM. Overall, 464 oocytes were retrieved, of which 274 were mature. Following IVM, the number of total mature oocytes increased to 399 (45% increase in mature oocyte yield, P<0.0001). Fertilization rate after IVM was statistically significantly higher than the fertilization of already mature oocytes at retrieval (86% versus 73%, respectively, P<0.05). The total number of oocytes and embryos frozen before IVM was 207 (45% of all oocytes retrieved). This number increased to 320 (69% of all oocytes retrieved) following IVM (P<0.0001). IVM is a useful strategy to improve the mature oocyte yield of fertility preservation cycles. Immature oocytes retrieved during oocyte/embryo cryopreservation cycles should not be discarded to improve the future potential of fertility.

Fertility preservation in breast cancer patients: IVF and embryo cryopreservation after ovarian stimulation with tamoxifen.

BACKGROUND: Breast cancer chemotherapy commonly causes premature ovarian failure and infertility. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, natural cycle IVF (NCIVF) has been used to preserve fertility and treat infertility in these women. METHODS: Twelve women with breast cancer received 40-60 mg tamoxifen for 6.9 +/- 0.6 days beginning on days 2-3 of their menstrual cycle (15 cycles), and had IVF (TamIVF) with either fresh embryo transfer (six cycles) or cryopreservation (nine cycles). They were compared to a retrospective control group (n = 5) who had natural cycle IVF (NCIVF, nine cycles). RESULTS: Cycle cancellation was significantly less frequent in TamIVF, compared with NCIVF (1/15 versus 4/9, P < 0.05). Compared with NCIVF, TamIVF patients had a greater number of mature oocytes (1.6 +/- 0.3 versus 0.7 +/- 0.2, P = 0.03) and embryos (1.6 +/- 0.3 versus 0.6 +/- 0.2, P = 0.02) per initiated cycle. TamIVF resulted in the generation of embryo(s) in every patient (12/12) while only three out of five patients had an embryo following NCIVF. Two out of six patients in TamIVF, and 2/5 in NCIVF conceived. One patient in the TamIVF group delivered a set of twins. After a mean follow up of 15 +/- 3.6 months (range 3-54), none of the patients had a recurrence of cancer. CONCLUSIONS: Tamoxifen stimulation appears to result in a higher number of embryos and may provide a safe method of IVF and fertility preservation in breast cancer patients.

Effect of initial gestagen treatment on bleeding patterns in postmenopausal women receiving continuous combined hormone replacement therapy.

OBJECTIVE: The purpose of this prospective study was to investigate the association of initial gestagen treatment with future breakthrough bleedings during continuous combined hormone replacement therapy. The predictability of progesterone challenge test on bleeding has also been investigated. DESIGN: Eighty-six naturally postmenopausal women, of whom 38 received initial gestagen treatment (5 mg medroxyprogesterone acetate, twice daily, for 10 days) and 48 did not, were included in this prospective study. Patients were followed for 6 months, and any bleeding occurring during therapy was recorded. RESULTS: Of the 48 patients who received continuous combined hormone replacement therapy without initial gestagen treatment, 23 (48%) had a bleeding episode. Of the 38 patients who received the same therapy with initial gestagen treatment, 13 (34.2%) had bleeding. There was a trend toward decreased breakthrough bleeding in the second group, which did not achieve significance. The mean time before bleeding was 6.76 weeks in the first group and 11.75 weeks in the second group; the difference was statistically significant (p < 0.05). Of the 28 patients with a negative progesterone challenge test at the onset of therapy, eight (28.6%) had bleeding during hormone replacement therapy. Of the 10 patients with a positive challenge, five (50%) had bleeding. The difference was not statistically significant. CONCLUSIONS: Patients who receive gestagen treatment before the onset of continuous combined hormone replacement therapy tend to experience breakthrough bleeding less frequently and later during the therapy. The response to progesterone challenge does not predict future bleeding during continuous combined hormone replacement therapy.

Endometrial disease diagnosed by transvaginal ultrasound and dilatation and curettage.

BACKGROUND: This study is designed to compare endometrial thickness measured by transvaginal ultrasound with endometrial pathology by dilatation and curettage. METHODS: Fifty-four women with postmenopausal bleeding were evaluated. Endometrial thickness, including both layers of the endometrium, was measured by transvaginal ultrasound after which fractional curettage was performed and samples taken were then dispatched for histologic examination. RESULTS: Median endometrial thicknesses of 5 mm, 8.5 mm and 6 mm were found for benign, hyperplastic and carcinomatous endometrium, respectively. Of the eight hyperplastic samples, two cases had 4 mm, and one case had 3mm endometrial thickness. Similarly, of the nine malignant samples, three cases had an endometrial thickness of 3 mm. Three mm has been found to be the best cut off point for endometrial abnormalities in postmenopausal bleeding with 100% sensitivity but low specificity (13%). CONCLUSION: Fractional curettage seems to be the best method for detecting endometrial abnormalities in women with postmenopausal bleeding.

Relationship between circulating estradiol levels, body mass index, and breakthrough bleeding in postmenopausal women receiving hormone replacement therapy.

OBJECTIVE: The purpose of this prospective study was to investigate the association of breakthrough bleeding with circulating estradiol levels and obesity in postmenopausal women receiving hormone replacement therapy. DESIGN: Fifty postmenopausal women receiving 0.625 mg conjugated estrogen with 2.5 mg medroxyprogesterone acetate were included in the study. Patients are recalled at 1st, 5th and 9th weeks for the measurements of the serum estradiol levels. RESULTS: Twenty women (40%) had a bleeding episode within 9 weeks of therapy. Of the 25 women who had a body mass index (BMI) of > 25, 13 (52%) had bleeding. Of the 25 women who had a BMI of < 25, 7 (28%) had bleeding. There was a trend toward a relation between BMI and breakthrough bleeding, although the relation did not achieve significance (p = 0.14). Serum estradiol levels of both bleeders and nonbleeders remained similar throughout the study. Endometrial histology revealed proliferative endometrium in two cases and secretory endometrium in one case at baseline; two cases of proliferative endometrium were found during bleeding. The remaining samples revealed atrophy. CONCLUSIONS: No relation was found between serum estradiol levels and breakthrough bleeding. Nevertheless, increased BMI may have an impact on breakthrough bleeding in postmenopausal women receiving hormone replacement therapy.