Molecular phenotypes of bovine blastocyst derived from in vitro-matured oocyte supplemented with PAPP-A.

Insulin-like growth factor-1 (IGF-1) regulates cellular lipid content, whereas pregnancy-associated plasma protein-A (PAPP-A) increases IGF-1 bioavailability. Using in vitro-matured cumulus-oocyte complexes, we aimed to evaluate the impact of PAPP-A on the blastocyst lipid content, embryo cryotolerance and embryonic transcriptional profile. We determined that PAPP-A did not affect the lipid content of oocytes, blastocysts, or blastocyst yield (P > 0.05). However, PAPP-A modulated the embryo transcriptional profiles by downregulating PPARGC1A and AKR1B1, which are related to lipid metabolism; CASP9, a pro-apoptotic gene; and IFN-τ, a marker of embryo quality (P < 0.05). Furthermore, the use of PAPP-A improved blastocyst re-expansion in the first 3 h of culture after vitrification (P < 0.05). Although PAPP-A did not affect the blastocyst lipid content or embryo production, we suggest that embryonic transcriptional modulation could contribute to maintain the balance in embryo lipid metabolism. Furthermore, PAPP-A's approach seems to control key intracellular pathways that improve post-cryopreservation development of blastocysts.

Are Serum Ferritin Levels a Reliable Cancer Biomarker? A Systematic Review and Meta-Analysis.

Although serum ferritin (SF) has been shown in several studies to be a potential cancer biomarker, the results are inconsistent. Herein, a systematic review was performed to investigate the clinical SF levels in different types of tumors in order to verify the role of SF levels as a biomarker for cancer diagnosis. The search was performed using the PubMed/Medline, Cochrane Library, and Scopus databases. Observational studies comparing SF levels between healthy adults and patients with cancer were included. The meta-analysis was carried out according to the inverse variance and random effects model. The standardized mean differences (SMDs) were assessed at 95% confidence intervals (CIs). We found that SF was higher in patients with cancer (SMD 3.07; CI 1.96,4.17), especially for head and neck cancer (SMD 3.88; CI 0.42,7.34), lung cancer (SMD 1.72; CI 0.67,2.78), pancreatic cancer (SMD 6.79; CI 5.66,7.91), and renal cell carcinoma (SMD 1.77; CI 0.48,3.05). Moreover, in the advanced stages (Stages III and IV), ferritin levels were higher than in healthy adults (SMD 4.89; CI 2.72,7.06, and SMD 8.40; CI 6.99,9.82, respectively). SF acts as a biomarker for pancreatic cancer, renal cell carcinoma, lung cancer, and head and neck cancer and is a sensitive biomarker for the detection of advanced stages of tumors.

Preventive training does not interfere with mRNA-encoding myosin and collagen expression during pulmonary arterial hypertension.

To gain insight on the impact of preventive exercise during pulmonary arterial hypertension (PAH), we evaluated the gene expression of myosins and gene-encoding proteins associated with the extracellular matrix remodeling of right hypertrophied ventricles. We used 32 male Wistar rats, separated in four groups: Sedentary Control (S, n = 8); Control with Training (T, n = 8); Sedentary with Pulmonary Arterial Hypertension (SPAH, n = 8); and Pulmonary Arterial Hypertension with Training (TPAH, n = 8). All rats underwent a two-week adaptation period; T and TPAH group rats then proceeded to an eight-week training period on a treadmill. At the beginning of the 11th week, S and T groups received an intraperitoneal injection of saline, and SPAH and TPAH groups received an injection of monocrotaline (60 mg/kg). Rats in the T and TPAH groups then continued with the training protocol until the 13th week. We assessed exercise capacity, echocardiography analysis, Fulton's index, cross-sectional areas of cardiomyocytes, collagen content and types, and fractal dimension (FD). Transcript abundance of myosins and extracellular matrix genes were estimated through reverse transcription-quantitative PCR (RT-qPCR). When compared to the SPAH group, the TPAH group showed increases in functional capacity and pulmonary artery acceleration time/pulmonary ejection time ratio and decreases in Fulton's index and cross-sectional areas of myocyte cells. However, preventive exercise did not induce alterations in col1a1 and myh7 gene expression. Our findings demonstrate that preventive exercise improved functional capacity, reduced cardiac hypertrophy, and attenuated PH development without interfering in mRNA-encoding myosin and collagen expression during PAH.

Equine chorionic gonadotropin drives the transcriptional profile of immature cumulus-oocyte complexes and in vitro-produced blastocysts of superstimulated Nelore cows.

Studies have shown that the use of equine chorionic gonadotropin (eCG), which binds both follicle stimulating hormone (FSH) and luteinizing hormone (LH) receptors, could modify the female reproductive tract. We, thus, aimed to quantify the messenger RNA (mRNA) abundance of genes related to cumulus-oocyte complexes (COCs) and embryo quality in Nelore cows (Bos taurus indicus) submitted to ovarian superstimulation using only FSH (FSH group; n = 10) or replacement of the last two doses of FSH by eCG (FSH/eCG group; n = 10). All animals were slaughtered and the ovarian antral follicles from both groups (10-14 mm in diameter) were aspirated for cumulus, oocyte and in vitro embryo production gene expression analysis. The relative mRNA abundance of 96 genes related to COCs development and embryo quality was measured by RT-qPCR. We found that oocytes are more affected by eCG use and that 35 genes involved in lipid metabolism, oxidative stress, transcriptional control, and cellular development were upregulated in the FSH/eCG group. In blastocysts, lipid metabolism seems to be the main pathway regulated by eCG use. We suggest that these multiple effects could be due to the ability of eCG to bind LHR and FSHR, which could activate multiple signal transduction pathways in the superstimulated ovary, further impacting the transcriptional profile of COCs and blastocysts.

Extracellular vesicles of follicular fluid from heat-stressed cows modify the gene expression of in vitro-matured oocytes.

The effect of heat stress (HS) on cattle reproduction is deleterious with respect to ovarian follicular development and oocyte quality. The objective of this study was to investigate the effect of follicular fluid extracellular vesicles (EVs) obtained from cows maintained in thermoneutral (TN) or HS conditions on in vitro oocyte maturation. Nonlactating cows were estrous synchronized. Immediately after ovulation day (D1), the cows were randomly assigned to TN or HS environments. Follicular fluid from all follicles from each treatment was pooled, and EVs were obtained. Pools of 20 cumulus oocyte-complexes (COCs), were allocated to the following treatments: Control (n = 4 COC pools): matured in base medium; TN (n = 4 COC pools): matured in base medium supplemented with TN EV suspension; and HS (n = 4 COC pools): matured in base medium that was supplemented with the HS EV suspension. All treatments were conducted at 38.5 °C for 24 h in a humid atmosphere with 5% CO2. After maturation, the COCs were evaluated for meiotic progression, DNA integrity and oocyte quality-related gene expression. When the experimental groups were compared with the control group, a treatment effect was not observed for meiotic progression and DNA integrity. In the cumulus cells of TN group, there was relatively lesser expression of the IGFBP4 gene. In the oocytes of the TN as compared with the HS group, the IGFBP2, BMP15, GDF9, CDCA8, HAS2, RPL15, STAT3 and PFKP genes were expressed to a lesser extent. The findings indicated that oocytes matured in the presence of EVs from the follicular fluid of cows collected when there were TN conditions, however, there was a lesser expression of genes related to oocyte quality.