Serum Progesterone Concentrations Research Articles

Proliferation and apoptosis dynamics of the normal canine mammary gland during the oestrous cycle evaluated by Ki-67 and Caspase-3 indexes.

Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.

Supplementation of the Combination of Quercetin and Vitamin E Alleviates the Effects of Heat Stress on the Uterine Function and Hormone Synthesis in Laying Hens.

Chickens are sensitive to heat stress because their capacity to dissipate body heat is low. Hence, in chickens, excessive ambient temperature negatively influences their reproductive performance and health. Heat stress induces inflammation and oxidative stress, thereby rendering many reproductive organs dysfunctional. In this study, we evaluated the effects of the supplementation of dietary quercetin and vitamin E on the uterine function, eggshell quality via estrogen concentration, calcium metabolism, and antioxidant status of the uterus of laying hens under heat stress. The ambient temperature transformation was set at 34 ± 2 °C for 8 h/d (9:00 am-5:00 pm), which was followed by 22 °C to 28 °C for 16 h/d. Throughout the experiment, the relative humidity in the chicken's pen was at 50 to 65%. A total of 400 Tianfu breeder hens (120-days-old) were randomly divided into four dietary experimental groups, including basal diet (Control); basal diet + 0.4 g/kg quercetin; basal diet + 0.2 g/kg vitamin E; and basal diet + the combination of quercetin (0.4 g/kg) and vitamin E (0.2 g/kg). The results show that the combination of quercetin and vitamin E significantly increased the serum alkaline phosphatase levels and the antioxidant status of the uterus (p < 0.05). In addition, the combination of quercetin and vitamin E significantly increased the concentrations of serum estrogen and progesterone, as well as elevated the expression of hypothalamic gonadotropin-releasing hormone-1 and follicular cytochrome P450 family 19 subfamily A member-1 (p < 0.05). We also found that the calcium levels of the serum and uterus were significantly increased by the synergistic effects of quercetin and vitamin E (p < 0.05), and they also increased the expression of Ca2+-ATPase and the mRNA expression of calcium-binding-related genes in the uterus (p < 0.05). These results are consistent with the increased eggshell quality of the laying hens under heat stress. Further, the combination of quercetin and vitamin E significantly increased the uterine morphological characteristics, such as the height of the uterine mucosal fold and the length of the uterine mucosa villus of the heat-stressed laying hens. These results collectively improve the uterine function, serum and uterine calcium concentration, eggshell strength, and eggshell thickness (p < 0.05) in heat-stressed laying hens. Taken together, we demonstrated in the present study that supplementing the combination of dietary quercetin and vitamin E alleviated the effects of heat stress and improved calcium metabolism, hormone synthesis, and uterine function in the heat-stressed laying hens. Thus, the supplementation of the combination of quercetin and vitamin E alleviates oxidative stress in the eggshell gland of heat-stressed laying hens, thereby promoting calcium concentration in the serum and eggshell gland, etc., in laying hens. Hence, the combination of quercetin and vitamin E promotes the reproductive performance of the laying hens under heat stress and can also be used as a potent anti-stressor in laying hens.

Клинико-диагностические проявления ложной беременности у коз

The purpose of research is to study the clinical and diagnostic manifestations of false pregnancy in goats. The object of the study is replacement goats of breeding age (n = 6) and lactating goats (n = 37) of the Saanen breed, which were diagnosed with pseudopregnancy during a screening ultrasound examination for pregnancy and infertility. It has been established that anaphrodisia and hydrometra are obligatory symptoms of false gestation. Due to the accumulation of a significant amount of serous transudate in the uterine cavity, a pronounced bilateral symmetrical increase in abdominal volume was recorded in almost every third patient. Hydrometra was effectively recognized using ultrasound. During transabdominal scanning of pseudouterine goats, an accumulation of echo-negative fluid was visualized in the uterine cavity in the absence of the fetus (fetuses) and placentas. In the majority of sick goats (35 heads, or 81.4 %), the diagnosis was made on the hydrometer during the first ultrasound. Only 8, or 16.6 %, of the experimental goats required additional ultrasound to diagnose the hydrometer and differentiate it from a physiologically developing pregnancy. When analyzing the results of a study of the concentration of serum progesterone in pseudofetal goats, another characteristic feature of the pathology was revealed – moderate progesteronemia. It is interesting to note that the average progesterone values in pseudofetal goats were 3.5 times lower (P ≤ 0.01) than in clinically healthy goats with a gestation period of 50–90 days (4.50 ± 1.52 vs. 15.81 ± 1.32 ng/ml). Hematological and biochemical blood parameters in pseudopregnant goats did not have significant deviations from the norm and were comparable to those in clinically healthy goats with a physiologically developing pregnancy. Transabdominal visual echography is an informative method for diagnosing and differentially diagnosing false gestation from a physiologically developing pregnancy, which allows one-time (in 81.40 % of cases) or two-time examination of goats using the character¬ristic echo symptoms of hydrometers to make an accurate diagnosis of pseudo-pregnancy.

Epigenetic impact of hypothyroidism on the functional differentiation of the mammary gland in rats

Mammary gland (MG) lactogenic differentiation involves epigenetic mechanisms. We have previously shown that hypothyroidism (HypoT) alters the MG transcriptome in lactation. However, the role of thyroid hormones (T3 and T4 a. k.a. THs) in epigenetic differentiation of MG is still unknown. We used a model of post-lactating HypoT rats to study in MG: a) Methylation and expression level of Gata3, Elf5, Stat6, Stat5a, Stat5b; b) Expression of Lalba, IL-4Rα and Ncoa1 mRNA; c) Histone H3 acetylation and d) Estrogen and progesterone concentration in serum. HypoT increases the estrogen serum level, decreases the progesterone level, promotes methylation of Stat5a, Stat5b and Stat6, decreasing their mRNA level and of its target genes (Lalba and IL-4Rα) and increases the Ncoa1 mRNA expression and histone H3 acetylation level. Our results proved that HypoT alters the post-lactation MG epigenome and could compromise mammary functional differentiation.

Rapid label-free impedimetric detection of progesterone enhanced by immunomagnetic bead-based competitive immunoreaction

Detecting progesterone (P4) concentration in cow serum is essential for monitoring the pregnancy progress after fertilization and is significant for the dairy farming industry and veterinary medicine. This study reports enzyme-free immunomagnetic beads (IMBs)-based competitive immunoassay for detecting P4 by P4-bovine serum albumin (BSA)-modified biosensors. The anti-P4 antibody-conjugated IMBs serve as collectors to capture P4 in undiluted serum samples to prevent the biosensor surface from biosample contamination and as insulated labels to report the electron-transfer resistance signal of electrochemical impedance spectroscopy (EIS) measurement. The IMBs and P4-containing samples were mixed for 15−30 min, capable of obtaining stable P4@IMB complexes. The 0.2-kGauss pulsed magnetic field (PMF) of the 20-s pulse width and 20-s relaxation time applied for 5 min can shorten the immunoreaction time between the P4@IMBs and the P4-BSA-modified biosensor and reduce the IMB's nonspecific adsorption on the biosensor surface. This competitive immunoassay's cut-off value and detection limit were 7.71 ng/mL and 7.33 ng/mL, respectively, which is lower than the serum's P4 plateau concentration (over 8 ng/mL) of dairy cows on days 6–16 of estrus cycles and that in pregnancy. The IMB-based immunoassay combining the PMF attraction and the label-free EIS measurement exhibits promising potential for rapidly detecting P4 in undiluted serum.

Effect of intra-uterine administration of Lactobacillus bacteria on the steroid hormone profile in sub-clinical endometritis affected cows

Infertility in bovines is a major cause of serious economic loss to the dairy farmers. A major reason for infertility is sub-clinical, retrograde uterine infections. Sub-clinical endometritis is endometrial inflammation without apparent clinical manifestation and usually without signs of infection. This condition may be due to uterine infections or an extended inflammatory period that exists after elimination of bacteria. At present, infertility treatment is mainly done with intrauterine antibacterials, antiseptics and less commonly by hormones. These days, the major problem faced by animal reproductive health workers is the multiple drug resistance pathogens because of the indiscriminate use of antibiotics.Therefore, a different approach for more effective treatment of subclinical endometritis with Lactobacilli and its role on the steroid hormone profile was studied. In the present study, estradiol-17 β values were lower in the sub-clinical endometritis affected cows. Whereas, intra-uterine administration of Lactobacillus bacteria caused significant increase in estradiol level in a cycle after treatment in cross- bred cows. Similarly, the circulating serum progesterone concentration was also found to be low in subclinical endometritis affected cows. These findings could be used for clinical and experimental interpretations. Further, the information on pulsatile release of gonadotropins and steroid hormones status, receptors and its control, the close relationship among hormones could be necessary for better understanding of the role of steroid hormones in sub-clinical uterine infections.

Menstrual Cycle Phase Has No Influence on Performance-Determining Variables in Endurance-Trained Athletes: The FENDURA Project.

This study aimed to investigate the effect of the MC and endogenous sex hormone concentrations on performance-determining variables in three distinct MC phases in endurance-trained females. Twenty-one eumenorrheic trained/highly trained endurance athletes completed a standardized test battery during the early follicular phase (EFP), ovulatory phase (OP), and midluteal phase (MLP) for either one ( n = 7) or two test cycles ( n = 14). MC phases were determined using calendar-based counting, urinary ovulation testing, and verified with serum hormone analysis. MCs were retrospectively classified as eumenorrheic or disturbed. Disturbed MCs were excluded from analysis. The test battery consisted of 4-6 × 5-min submaximal stages with stepwise speed increases, a 30-s all-out double-poling ski ergometer test, and a maximal incremental treadmill running test. At a group level, there was no effect of MC phase or the serum concentrations of estrogen and progesterone on peak oxygen uptake (V̇O 2peak ), oxygen uptake at 4 mmol·L -1 blood lactate concentration, time to exhaustion, running economy, or mean 30-s power output (MPO 30s ). Serum testosterone concentration was positively associated with MPO 30s ( P = 0.016). Changes in V̇O 2peak from EFP to MLP were inconsistent between individuals and across cycles. None of the measured performance-determining variables were influenced by MC phase or serum estrogen or progesterone concentrations. Although some individual patterns could be observed, there was no indication that any single MC phase is consistently associated with improved or impaired V̇O 2peak on a group level.

Effect of Curcuma longa maceration treatment on ovarian follicular development, serum oestradiol, uterine growth and vascularisation in female albino rats.

Curcuma longa is a well-known medicinal plant with various health benefits. This study was designed to evaluate the administration of Indonesian C. longa maceration for its effect on promoting growth and development of the ovary and uterus before mating in female albino rats. A total of 15 female Sprague Dawley rats in their dioestrous phase were assigned into three different groups: the Control group (mineral water); the Cur-Low group (mineral water with 1% C. longa maceration) and the Cur-High group (mineral water with 5% C. longa maceration). The treatments were given for 20 days. Serum concentrations of follicle-stimulating hormone, oestradiol and progesterone were determined. After the sacrifice of the rats, ovary and uterine relative weight, uterine cornua diameter and length, uterine gland diameter (by histology), the number of primary, secondary, tertiary, and Graafian follicles, the number of corpora lutea and vascular endothelial growth factor (VEGF) expression in the ovary were measured. Uterine vascularisation was also evaluated. Administration of C. longa maceration significantly improved the relative weights of the uterus and ovary; uterine cornua diameter, length and vascularisation; uterine gland diameter; and expression of VEGF in the ovary. It also increased the number of tertiary follicles and corpora lutea, albeit not significantly. Follicle-stimulating hormone serum concentrations were lower in the administered rats. Oestradiol and progesterone levels rose with C. longa maceration treatment. The maceration improved the reproductive organs of unmated rats and had potential to optimise the uterine environment for supporting pregnancy in order to produce high-quality offspring.

Effect of High Energy Diet Supplementation during Periparturient Period on Ovarian Steroids and Reproductive Performance in Vrindavani Cows

The objective of the study was to assess the effect of high energy diet supplementation during periparturient period on ovarian steroids and reproductive performance in vrindavani cows. Postpartum vrindavani cows (n= 20) of second to fourth parity with lactation yield of &gt; 10 L/day were divided in to two groups (n=10 cow/group). Group I (CON) cows were fed with basal diet to serve as control. Group II (TRT) cows were provided with 20% extra concentrates in the form of energy. 20% additional concentrate diet was supplemented from second week to eight week after calving. Blood samples were collected at weekly interval from 4 week before calving to8weeks after calving. Blood samples were collected to determine estradiol (E2) and progesterone (P4) in the serum using RIA. Postpartum reproductive performance was assessed in terms occurrence of first postpartum estrus, calving to conception interval, conception rate and number of service per conception. Serum estradiol and progesterone concentration increased significantly(P&lt;0.05) from 2 to 8 week postpartum in Group II as compared to Group I. Marked significant(P&lt;0.05)improvement in the postpartum reproductive performance in terms of early occurrence of first postpartum estrus(67.0Vs 53.0), reduced calving to conception interval(85.87 Vs74.4), service per conception (1.62 Vs 1.2), days from calving to first AI(88.5 Vs 65.73), higher first AI conception rate(40 Vs 80%) and cumulative conception rate(88.52 Vs 65.73%) in group II as compared to group I. In conclusion, additional high energy diet supplemented group showed significant increased ovarian steroid hormonal concentrations and marked improvement in the reproductive performance in Vrindavani cows.

Can serum progesterone concentration direct a fresh or freeze-all transfer strategy in the first in vitro fertilisation cycle?

PurposeTo examine the interaction between serum progesterone concentration on the trigger day and choice of freeze-all and fresh transfer strategies on live birth in an unselected population as well as in patients over 35 years old.MethodsWe performed a retrospective cohort study of 26,661 patients commencing their first IVF cycle in a large fertility centre between 2015 and 2019, including 4687 patients over 35 years old. We performed a multivariable fractional polynomial interaction analysis within a logistic regression model to investigate the interaction between serum progesterone concentration and the choice of freeze-all or fresh transfer strategy following the first transfer.Results15,539 patients underwent a fresh embryo transfer and 11,122 underwent a freeze-all strategy in their first IVF cycle. The freeze-all group had a higher live birth rate compared to the fresh group (43.9% vs 40.3%). After adjusting for confounding factors, there was a positive interaction between serum progesterone concentrations and the choice of a freeze-all versus fresh embryo transfer on live birth (p for interaction 0.0001), with a larger magnitude of effect when progesterone concentration was higher. Such an interaction was also observed in patients over 35 years old (p for interaction 0.01), but the treatment effect curve over progesterone concentrations was almost flat.ConclusionsIn an unselected population, frozen transfer is associated with greater chances of live birth, especially in patients with higher serum progesterone concentration. In patients over 35 years old, the benefit of a freeze-all policy appears small across all serum progesterone concentrations.

Local effect of allopregnanolone in rat ovarian steroidogenesis, follicular and corpora lutea development

Allopregnanolone (ALLO) is a known neurosteroid and a progesterone metabolite synthesized in the ovary, CNS, PNS, adrenals and placenta. Its role in the neuroendocrine control of ovarian physiology has been studied, but its in situ ovarian effects are still largely unknown. The aims of this work were to characterize the effects of intrabursal ALLO administration on different ovarian parameters, and the probable mechanism of action. ALLO administration increased serum progesterone concentration and ovarian 3β-HSD2 while decreasing 20α-HSD mRNA expression. ALLO increased the number of atretic follicles and the number of positive TUNEL granulosa and theca cells, while decreasing positive PCNA immunostaining. On the other hand, there was an increase in corpora lutea diameter and PCNA immunostaining, whereas the count of TUNEL-positive luteal cells decreased. Ovarian angiogenesis and the immunohistochemical expression of GABAA receptor increased after ALLO treatment. To evaluate if the ovarian GABAA receptor was involved in these effects, we conducted a functional experiment with a specific antagonist, bicuculline. The administration of bicuculline restored the number of atretic follicles and the diameter of corpora lutea to normal values. These results show the actions of ALLO on the ovarian physiology of the female rat during the follicular phase, some of them through the GABAA receptor. Intrabursal ALLO administration alters several processes of the ovarian morpho-physiology of the female rat, related to fertility and oocyte quality.

Therapeutic potential of procathepsin L-inhibiting and progesterone-entrapping dimethyl-β-cyclodextrin nanoparticles in treating experimental sepsis.

The pathogenic mechanisms of bacterial infections and resultant sepsis are partly attributed to dysregulated inflammatory responses sustained by some late-acting mediators including the procathepsin-L (pCTS-L). It was entirely unknown whether any compounds of the U.S. Drug Collection could suppress pCTS-L-induced inflammation, and pharmacologically be exploited into possible therapies. Here, we demonstrated that a macrophage cell-based screening of a U.S. Drug Collection of 1360 compounds resulted in the identification of progesterone (PRO) as an inhibitor of pCTS-L-mediated production of several chemokines [e.g., Epithelial Neutrophil-Activating Peptide (ENA-78), Monocyte Chemoattractant Protein-1 (MCP-1) or MCP-3] and cytokines [e.g., Interleukin-10 (IL-10) or Tumor Necrosis Factor (TNF)] in primary human peripheral blood mononuclear cells (PBMCs). In vivo, these PRO-entrapping 2,6-dimethal-β-cyclodextrin (DM-β-CD) nanoparticles (containing 1.35 mg/kg PRO and 14.65 mg/kg DM-β-CD) significantly increased animal survival in both male (from 30% to 70%, n = 20, P = 0.041) and female (from 50% to 80%, n = 30, P = 0.026) mice even when they were initially administered at 24h post the onset of sepsis. This protective effect was associated with a reduction of sepsis-triggered accumulation of three surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF) by 40%; Macrophage Inflammatory Protein-2 (MIP-2) by 45%; and Soluble Tumor Necrosis Factor Receptor I (sTNFRI) by 80%]. Surface Plasmon Resonance (SPR) analysis revealed a strong interaction between PRO and pCTS-L (KD = 78.2 ± 33.7 nM), which was paralleled with a positive correlation between serum PRO concentration and serum pCTS-L level (ρ = 0.56, P = 0.0009) or disease severity (Sequential Organ Failure Assessment, SOFA; ρ = 0.64, P = 0.0001) score in septic patients. Our observations support a promising opportunity to explore DM-β-CD nanoparticles entrapping lipophilic drugs as possible therapies for clinical sepsis.

Spironolactone metabolite causes falsely increased progesterone in the Abbott Architect immunoassay

BackgroundImmunoassays are important for routine clinical testing and medical diagnosis. However, they are limited by cross-reactivity especially at low analyte concentrations. There is a critical need to investigate compounds that can interfere with immunoassays. Herein, we describe the identification of canrenone, a spironolactone metabolite that falsely increases progesterone concentrations on the Abbott Architect i2000 Immunoassay. MethodsSerum samples and assay diluents were spiked with spironolactone or canrenone and progesterone concentrations were measured on the Architect i2000 and Immulite XPi immunoassay platforms. Blood samples from patients taking spironolactone were analyzed with liquid chromatography-tandem mass spectrometry to evaluate the intrinsic response of progesterone concentrations to the presence of canrenone. ResultsWe measured approximately 10-fold higher progesterone concentrations on the Abbott Architect i2000 compared to reference immunoassay analyzers (Siemens Immulite XPi and Roche Cobas e601/602), suggesting an analytical error which is unique to the Architect i2000 antibody and/or assay conditions. By measuring serum progesterone after addition of spironolactone or canrenone to serum samples, we found that canrenone falsely increased progesterone on the Architect i2000 immunoassay. However, this interference was more pronounced at low serum progesterone concentrations. Moreover, a strong positive correlation was seen between canrenone and measured serum progesterone concentrations. ConclusionsOur investigations are important for individuals who require progesterone measurements using the Architect i2000 immunoassay, especially because it is unlikely for clinicians to order canrenone measurements alongside progesterone measurements for individuals taking spironolactone. Further research is needed to determine whether canrenone can influence progesterone measurements on other immunoassay systems.

A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy

BackgroundConcomitant use of efavirenz-based antiretroviral therapy and a standard-dose etonogestrel contraceptive implant resulted in 82% lower etonogestrel exposure compared to women not receiving antiretroviral therapy. The clinical impact of this reduced exposure is supported by retrospective cohort evaluations which demonstrated higher rates of unintended pregnancies when contraceptive implants were combined with efavirenz. We hypothesized that placement of two etonogestrel implants in those taking efavirenz-based antiretroviral therapy could increase etonogestrel exposure and improve measures of contraceptive efficacy. ObjectivesThis study compared the rate of ovulation and etonogestrel pharmacokinetics in women on efavirenz-based antiretroviral therapy receiving two etonogestrel implants (136mg, DoublET group) versus one etonogestrel implant (68mg, Control group). Study DesignThis randomized, open-label study enrolled Ugandan women with regular menstrual periods who were receiving efavirenz-based antiretroviral therapy for treatment of HIV. Participants were randomized 1:1 to the DoublET or Control group, and the etonogestrel implant(s) were placed in the same arm at enrollment. All participants used a copper intrauterine device to prevent pregnancy. Ovulation was evaluated by weekly serum progesterone concentrations measured over 4 consecutive weeks at months 3 (weeks 9-12), 6 (weeks 21-24), and 12 (weeks 45-48). Progesterone concentrations >3ng/mL were interpreted as ovulation. The ovulation rate in each group was compared using Fisher’s exact test by month and generalized estimating equations over 48 weeks. Plasma was collected at day 3 and weeks 1, 4, 12, 24, 36 and 48 after implant placement, and analyzed by a validated LC-MS/MS method for etonogestrel. Etonogestrel concentrations were summarized as median (interquartile range, IQR) and compared between groups by geometric mean ratio (GMR) with 90% Confidence Interval (CI). ResultsAll participants (n=72) were cisgender Ugandan women, median age 31 (IQR 29, 36), and 36 participants were enrolled in each study group. Two participants in the Control group were discontinued; one at week 1 due to undetected pregnancy at entry and another at week 45 due to clinically significant depression. There were 47 ovulations over 104 person-months (45%) in 25 of 34 participants in the Control Group, and 2 ovulations over 108 person-months (2%) in 2 of 36 participants in the DoublET group [Month 3: 11 (31%) vs 0 (0%); Month 6: 17 (49%) vs 0 (0%); Month 12: 19 (56%) vs 2 (6%), respectively (all p<0.001)]. The odds of ovulation were reduced by 97.7% (95% CI: 90.1- 99.5) in the DoublET group over 48 weeks. At each time point, etonogestrel was more than two-fold higher in the DoublET group compared to controls (GMR 2.30-2.83), with the GMR of 2.83 (1.89, 3.35 90% CI) at week 48. There were no differences in the adverse events between groups and no participant discontinued due to adverse events. ConclusionOver 48 weeks of combined use, placing two etonogestrel implants suppressed ovulation and increased plasma etonogestrel exposure compared to one etonogestrel implant among women on efavirenz-based antiretroviral therapy. Doubling the dose of etonogestrel with efavirenz-based antiretroviral therapy could improve contraceptive effectiveness.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BackgroundOlanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. MethodsRats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5–40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. ResultsIn adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. ConclusionsThese results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

Second trimester maternal serum progesterone and estradiol concentrations with live and demised fetuses: Secondary analysis results from a randomized controlled trial

AbstractObjectiveTo provide data on maternal levels of estradiol and progesterone in the second trimester of pregnancy with a live foetus and those complicated by a spontaneous foetal demise.MethodsWithin a randomised trial to assess efficacy of mifepristone in termination following foetal demise from 14 to 28 weeks of gestation, we measured progesterone and estradiol levels in trial patients and in women undergoing termination with a live foetus. Women admitted to King Edward Memorial Hospital (Western Australia) from 2013 to 2016 were considered for eligibility and enroled. Scatter plots with 95% confidence intervals were generated for hormone levels by gestation. Generalised linear models were used to estimate mean values of estradiol and progesterone, accounting for maternal age, gestation and parity.ResultsOverall, women with a foetal demise had lower estradiol levels compared to women with a live foetus, (mean difference of 10 460 pmol/L). With a live foetus, higher levels of estradiol were observed with increasing gestations: with a mean of 17 010 pmol/L at 14 ≤ 17 weeks, 31 180 pmol/L at 23–28 weeks and similarly progesterone with a mean of 113 nmol/L at 14 ≤ 17 weeks and 183 nmol/L at 23–28 weeks. Progesterone levels in women with foetal demise were 37 nmol/L higher than women in the live foetus group. In all women, each unit increase in parity was associated with a decrease of 10nmol/l of progesterone (95% confidence interval: 4–16, p = 0.001).ConclusionsEstradiol and progesterone levels in the second trimester vary between pregnant women with a live and demised foetus.

Engineered exosome as a biological nanoplatform for drug delivery of Rosmarinic acid to improve implantation in mice with induced endometritis

Endometritis is an inflammatory and histopathologic disease in uterine tissues that interferes with the proper decidualization and implantation of the embryo. In this study, rosmarinic acid (RA) is used as an anti-inflammatory agent that encapsulates in exosomes and is used to attenuate lipopolysaccharide (LPS)-induced endometritis and improve implantation. For this purpose, exosomes were loaded with RA and then administrated into the animal groups, including RA, exosome, RA plus exosome (RA + Exo), and RA-loaded exosomes (RALExo) groups. The concentrations of RA or exosomes used in this study were 10 mg/kg, and the compounds were injected into the uterine horn 24 h following the induction of endometritis. Upon the presence of inflammation detected by the histopathological method, the most proper groups were mated with male mice. The effect of the treatment group on the implantation rate, progesterone levels, and gene expressions were assessed by Chicago Blue staining, enzyme-linked immunosorbent assay (ELISA), and Quantitative PCR (qPCR), respectively. Results showed RALExo10 and RA10 + Exo10 groups improved pathological alterations, enhanced progesterone levels, increased implantation rate, as well as heightened expression levels of Leukemia inhibitory factor (LIF) and Mucin-16 (MUC-16) genes. Besides, the expression levels of inflammatory cytokines, including Transforming growth factor-β (TGF-β), Interlukine-10 (IL-10), Interlukine-15 (IL-15), and Interlukine-18 (IL-18), were regulated. Our findings indicated that the expression of LIF, Muc-16 genes as well as IL-18, were significantly correlated with serum progesterone concentrations and the implantation rate in the treatment groups. The RALExo10 and RA10 + Exo10 groups showed ameliorated implantation rates in experimental groups.

Progesterone concentrations on blastocyst transfer day in modified natural cycle frozen embryo transfer cycles

Research questionAre serum progesterone concentrations on the day of modified natural cycle (mNC) frozen blastocyst transfer (FET) without luteal phase support (LPS) associated with clinical pregnancy rate (CPR)? DesignData were collected between January 2019 and October 2022 as a sub-study of an ongoing randomized controlled trial assessing pregnancy outcomes in mNC-FET. The sub-study included all women (n = 209) randomized to mNC-FET without LPS at the time of data extraction. Participants were aged 18–41 years, had regular menstrual cycles and underwent mNC-FET treatment with single-blastocyst transfer. Associations between the serum progesterone concentration on the day of blastocyst transfer and CPR, pregnancy rate and pregnancy loss rate (PLR) were examined between groups with low and higher progesterone concentrations using the 25th and 10th percentiles as cut-offs. Multivariate logistic regression analyses were performed to adjust for potential confounding factors. ResultsProgesterone concentrations on the day of blastocyst transfer in mNC-FET without LPS ranged from 4.9 to 91.8 nmol/l, with the 25th and 10th percentiles at 29.0 nmol/l and 22.5 nmol/l, respectively. Serum progesterone concentrations did not differ between women with or without a clinical pregnancy (mean [SD] 38.5 [14.0] versus 36.8 [12.4] nmol/l; P = 0.350). Furthermore, the CPR, pregancy rate and PLR were similar in women with low or high progesterone concentrations when using the 25th or the 10th progesterone percentile as cut-off. Multivariate regression analyses showed no association between progesterone concentrations and CPR. ConclusionsNo association was found between progesterone concentration on the day of blastocyst transfer and pregnancy outcome in women undergoing mNC-FET without progesterone LPS.

Assessment of Vcheck® analyzer for rapid progesterone concentration measurement including recommendations for achieving the optimal breeding time in bitches

Background and Aim: Serum progesterone concentration plays critical role in determining the optimal breeding time in bitches and diagnosing reproductive-related issues. This study aimed to conduct a comparative analysis of serum progesterone results obtained from commercial point-of-care immunological analyzers, namely, Vcheck®, with those obtained using chemiluminescent microparticle immunoassay (CMIA). Our overarching goal was to evaluate these analyzers’ accuracy and establish standardized guidelines for optimal breeding timing. Materials and Methods: Ninety-four serum samples from bitches were analyzed using the Vcheck® analyzer and compared with CMIA. Thorough documentation included the mean, standard deviation, 95% confidence interval (CI), and minimum and maximum values of serum progesterone concentrations. Furthermore, Pearson’s correlation coefficient, Lin’s concordance correlation coefficient, and the bias correction factor were meticulously recorded. Results: The mean progesterone concentration measured using the Vcheck® analyzer was significantly lower than that measured using CMIA, with a mean difference of 1.26 ng/mL of serum. The Bias correction factor was 0.935, which was nearly 1.00, indicating that the line of best-fit was on the perfect line of agreement, providing insight into the measurement accuracy. Pearson’s correlation coefficient, a measure of precision, was also close to 1 (0.939), confirming the reliability of the data. Furthermore, Lin’s concordance correlation coefficient was 0.877, indicating a fair overall agreement between the Vcheck® and CMIA methods. These results support the validity of the Vcheck® analyzer’s results. The present study was developed by aligning with established CMIA guidelines and adapting them using the range and 95% CI derived from each set of results, ensuring a standardized and rigorous approach. Conclusion: The Vcheck® analyzer provides a rapid assessment of serum progesterone concentration in bitches, with results comparable to those measured using the CMIA technique. However, when considering the use of the Vcheck® analyzer, it is recommended that the results should be interpreted carefully and the interpretation guidelines should be followed. In conclusion, Vcheck® provides a reliable and convenient method for veterinarian practitioners to measure canine progesterone levels in a clinical/hospital setting. Keywords: chemiluminescent microparticle immunoassay, optimal breeding time, progesterone, Vcheck®.

A Precision Assessment of a Point-of-Care Immunological Analyzer for Swift Progesterone Measurement and Guidance for Determining the Optimal Breeding Time in Bitches

The measurement of serum progesterone often varies due to different laboratory methodologies and individual canine characteristics. In this investigation, serum progesterone outcomes obtained from a commercial point-of-care immunological analyzer, designed for efficient serum progesterone assessment in bitches, were compared with results derived from chemiluminescent microparticle immunoassay from reference laboratories in Thailand. Our thorough documentation encompassed various parameters: mean, standard deviation, 95% confidence interval, and minimum and maximum serum progesterone concentration values. Additionally, we meticulously recorded the Pearson’s correlation coefficient, Lin’s concordance correlation coefficient, and the bias correction factor. Interestingly, there was no significant difference (p &gt; 0.05) in the means obtained by the point-of-care immunological analyzer and chemiluminescent microparticle immunoassay. The Pearson’s correlation coefficient between the point-of-care immunological analyzer and chemiluminescent microparticle immunoassay stood at 0.957, with Lin’s concordance correlation coefficient for point-of-care immunological analyzer recorded as 0.949. Furthermore, the bias correction factor was established at 0.991. This investigation followed established chemiluminescent microparticle immunoassay guidelines, modified to incorporate the mean and 95% confidence interval as criteria for optimal breeding time using the point-of-care immunological analyzer. In conclusion, the commercial point-of-care immunological analyzer emerges as a valuable tool, aiding in precisely determining the optimal timing for natural mating or artificial insemination in bitches.