Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.

[Reproductive problems in women with PCOS, the impact of PAI-1 carriers of 4G PAI-1 polymorphism and BMI].

Approximately 7-12% of women in reproductive age are affected by PCOS[2] and 40 to 70 percent of them are overweight contributing to the clinical picture of PCOS and increased reproductive and metabolic disorder. In order to investigate the role of PAl-1 as a possible risk factor for the development of PCOS a group of 67 women with polycystic ovarian disease and 70 healthy controls were investigated for levels of PAl-1 and carriage of the promoter polymorphism 675 4G/5G in gene of PAI-1. The correlation with BMI was checked. The results of the DNA analysis showed a high carriage of polymorphism 675 4G/4G in promoter of PAl-1 gene in women with PCOS but not significant (OR = 1.655; p = 0.141), as well in the total group of the patient (OR =1.474; p>0.05). Serum levels of PAI-1 were significantly higher in total group of patients compared to controls. The levels of PAI-1 is correlated with carriage of 675 4G/5G polymorphism in the gene for PAI-1 (r=0.534; p=0.03) as well as with BMI, like correlation coefficients were higherin the group with PCOS (0.572; p=0.04). Data from the disease history showed a higher percentage of women with reproductive problems: early pregnancy loss 48.5% and infertility 23.2%, significantly higher in the group with PCOS (58.1% compared to 32.4%). The carriers of polymorphism 4G are at greater risk for early pregnancy loss than those with 5G (61.45% as compared to 36.8%), which confirms that carriage of the polymorphism 4G/5G 675 gene PAl-1 has a specific in multifactorial pathogenesis and expression of PCOS.

[Reproductive problems in women with PCOS, the impact of PAL-1 CARRIERS OF 4G PAI -1 polymorphism and BMI].

Approximately 7-12% of women in reproductive age are affected by PCOS[2] and 40 to 70 percent of them are overweight contributing to the clinical picture of PCOS and increased reproductive and metabolic disorder. In order to investigate the role of PAl-1 as a possible risk factor for the development of PCOS a group of 67 women with polycystic ovarian disease and 70 healthy controls were investigated for levels of PAI-1 and carriage of the promoter polymorphism 675 4G/5G in gene of PAl-1. The results of the DNA analysis showed a high carriage of polymorphism 675 4G/4G in promoter of PAI-1 gene in women with PCOS but not as significant (OR = 1.6645, p = 0.141). Serum levels of PAI-1 were significantly higher in total group of patients compared to controls. The levels of PAI-1 is correlated with carriage of 675 4G/5G polymorphism in the gene for PAI-1 (R = 0.534, p = 0.03) as well as wih BMI, like correlation coefficients were higher in the group with PCOS (0.572, p = 0.04). Data from the disease history showed a higher percentage of women with reproductive problems: 61.5% (early pregnancy loss and infertility) significantly higher in the group with PCOS (70.1% compared to 54.1%). The carriers of polymorphism 4G are at greater risk for early pregnancy loss than those with 5G (61.45% as compared to 36.8%), which confirms that carriage of the polymorphism 4G/5G 675 gene PAI-1 has a specific in multifactorial pathogenesis and expression of PCOS.

[Terminated pregnancy following prenatal diagnosis of congenital anomalies--a part of register of congenital anomalies].

UNLABELLED: The most of European registries of congenital anomalies (CA) collected information of CA in livebirths, stillbirths and terminated pregnancies following prenatal/ultrasound diagnosis. OBJECTIVES: to assess terminated pregnancies after prenatal/ ultrasound diagnosis of CA as a part of register of CA performed in University Hospital-Pleven. Among 21 202 births monitored during the study period (1996-2005), 679 CA were detected. The total prevalence of CA was 32/ 1000 births. The outcome of pregnancy for all cases of selected CA by register was 620 livebirths (91.3%), 36 stillbirths (5.3%), 23 terminated pregnancies (TP) (3.4%). The percentage of pregnancy termination was higher in the case of isolated anomalies, mainly lethal and CA associated with a low survival rate (61%), than with multiple ones. The most common CA detected after prenatal/ ultrasound diagnosis were neural tube defects (NTD) - the main reason for TP (52% of cases). The low proportion of these CA in TP (1/3) compared to their proportion in livebirths (50%) demonstrated an insufficiency of prenatal diagnosis of NTD as a part of register of CA performed in University Hospital-Pleven. Prenatal diagnosis of CA allows an early genetic counseling of mother presenting information on neonatal prognosis and recurrence risk for subsequent pregnancies. It helps family to take an adequate decision for termination of pregnancy with bad prognosis about heavy fetal CA.

[Active screening for genetic pathology in newborns. I. Registration of congenital abnormalities]. / Aktiven skrining za genetichna patologiia sred novorodeni. I. Registratsiia na vrodeni anomalii.

Active screening for genetic pathology over a period of 12 years (1990-2001) involved examination of 29,629 newborns at the Clinic of Obstetrics and Gynaecology. Congenital anomalies were detected in 1244 cases (live-, stillbirths and terminated pregnancies) which gives an average incidence rate of 42.0 per 1000 among the studied population. Congenital cardiac anomalies and CA of the central nervous system were the most common types of isolated CA. They provided frequencies of 7.76 per 1000 and 6.85 per 1000 cases respectively. The incidence of the neural tube defects (NTD), particularly, varied throughout the years (t = 2.69; p < 0.01) but stated high--on average 2.12 per 1000 with the highest rate of 3.89 per 1000 in 1993. A reduction in the incidence of NTD is possible with a recommendation of periconceptional folic acid supplementation. Registration of CA is a strategy for identifying families at risk to give births of child with CA. This approach enabled us to provide more accurate genetic counselling and prenatal diagnosis for genetic pathology. Active screening of newborn population is likely to be an effective and necessary service.

[Use of recombinant factor VIIa for the control of massive bleeding caused by uterine hypotonia in post-placental period]. / Prilozhenie na rekombinanten faktor VIIa za kontrol na masivno kruvotechenie v sledplatsentarnia period, dulzhashto se na matochna khipotonia.

We report our clinical opinion for recombinant activated factor VII (NovoSeven, Novo Nordisk, Copenhagen, Denmark) administration in puerperae with massive haemorrhage caused by uterine hypotonia. Four women with severe bleeding in post-placental period received NovoSeven in bolus IV. The blood loss and laboratory changes in hematology and haemostasis parameters are monitored. The right time of application and the mean effective dose of the medication are discussed. The bleeding was ceased in all cases. Decrease in values of Hb, Er and PTT was noted. The mean administered dose of 72 micrograms/kg BW was effective. The laboratory values showed tendency for improvement on the 24 hour after administration and normal levels on discharge. The use of recombinant factor VIIA in puerperae with severe bleeding in the postplacental period is effective and safe enough and could be an alternative to the extreme surgical procedures.

[The treatment of tubal pregnancy with methotrexate]. / Lechenie na tubarna bremennost s metotreksat.

After a brief review on the possibilities for conservative treatment of tubal pregnancy the authors described a woman with left tubal pregnancy, in whom metotrexat was used successfully in a dose of 20 mg 4 times every other day administered intramuscularly. The right uterine tube of the woman was removed during the preceding ectopic pregnancy. The patency of the remaining tube was examined after a 2-month period, during which anti-inflammatory treatment was performed as well. An opinion is given that such conservative treatment should be used only in strictly diagnosed patients and with the single aim-preservation of reproductive capabilities of the woman, when there is no other way of treatment. When there are no reproductive aims, the operative method is recommended.