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Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17&alpha, OH progesterone (17&alpha, OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4&ndash, 13.8) vs. 3.7 (2.5&ndash, 4.7) IU/L, p &lt, 0.0001), LH/FSH (1.6 (1.0&ndash, 2.3) vs. 0.7 (0.5&ndash, 1.1), 0.0001), 17&alpha, &ndash, OHP (4.1 (3.2&ndash, 5.1) vs. 3.4 (2.7&ndash, 3.8) nmol/L, p = 0.0071), cortisol (464.0 &plusmn, 147.6 vs. 284.0 &plusmn, 129.7 nmol/L, 0.0001), prolactin (266.0 (175.0&ndash, 405.0) vs. 189.0 (142.0&ndash, 269.0) mIU/L, p = 0.0141), T (1.9 (1.2&ndash, 2.5) vs. 0.8 (0.7&ndash, 1.1) nmol/L, 0.0001), androstenedione (15.8 (11.6&ndash, 23.2) vs. 8.3 (6.5&ndash, 10.8) ng/mL, 0.0001), AMH (9.5 (7.5&ndash, 14.9) vs. 5.8 (3.8&ndash, 6.9) ng/mL, 0.0001), FAI (5.5 (2.8&ndash, 7.0) vs. 1.6 (1.1&ndash, 2.3), 0.0001), SHBG (37.0 (24.7&ndash, 55.5) vs. 52.9 (39.0&ndash, 67.6) nmol/L, p = 0.0136), DHEAS (6.8 &plusmn, 3.2 vs. 5.1 &plusmn, 1.5 &mu, mol/L, p = 0.0039), and leptin (38.7 &plusmn, 27.1 vs. 23.7 &plusmn, 14.0 ng/mL, p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level &gt, 7.20 ng/mL, FAI &gt, 2.75, androstenedione &gt, 11.45 ng/mL, total T &gt, 1.15 nmol/L, LH/FSH ratio &gt, 1.23, and the volume of each ovary &gt, 10.70 cm3 (for each criterion sensitivity &ge, 75.0&ndash, 93.0%, specificity &ge, 83.0&ndash, 93.0%). The diagnostic accuracy of PCOS determination was 90.2&ndash, 91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 &minus, (1.73 &times, AMH) &minus, (0.12 &times, Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.

Most studies have considered the negative influence of obesity on fertility in both genders. In the present study, we assessed mitochondrial activity expressed as the mitochondrial potential index (MPI) in cumulus cells from obese women and women with a normal body mass index (BMI) during assisted reproductive therapy. The results revealed a significant reduction of MPI with increased body mass. The lower MPI levels in cumulus cells from obese women may reflect mitochondrial dysfunction caused by oxidative stress, which can affect the cumulus-oocyte complex and have an impact on oocyte development., Highlights • Reduction of MPI in cumulus cells with increase of body mass is revealed. • Correlation between cumulus cell MPI and serum level of adipokines was observed. • Decrease of MPI in cumulus from obese women reflects impaired mitochondrial activity.

The biological properties of bee drone brood make it an ideal additive for growth promotion in animal husbandry instead of banned hormonal anabolics and antibiotics. However, the drone brood action on mammalian ovaries has not been well studied. The present study analyzes the impact of drone brood homogenate (DBH) in the diet of growing gilts on folliculogenesis. Large White female pigs at the age of 35 days were randomly divided into two groups of 10 animals each, and fed with the same basal diets. The experimental group was supplemented with 25 mg/kg forage of DBH for 180 days, after which the animals were slaughtered and morphometric, histological and immunohistochemical evaluation of their ovaries was performed. In addition, the expression of ovarian growth factors BMP15 and GDF9 in oocytes and cumulus cells was analyzed by RT-PCR. A significant increase in body weight and average daily gain at day 145 in the DBH-supplemented group was established. The length of the ovaries in the treated animals also was enhanced. More pools of primordial follicles, involved in intensive growth, as well as a larger diameter of primary and tertiary follicles were found in the ovaries of DBH-supplemented animals. These findings corresponded with an increase in the expression of GDF9 mRNA in the oocytes and cumulus cells. At the same time, signs of atresia in the Graafian follicles of treated animals were observed. The supplementation with DBH stimulates the early stages of folliculogenesis in gilts, but provokes atresia in the last stage of follicular development., Biološka svojstva pčelinjeg trutovskog legla čine ga idealnim dodatkom za poboljšanje rasta u stočarstvu umjesto zabranjenih hormonskih anabolika i antibiotika. Ipak, utjecaj trutovskog legla na jajnike u sisavaca još uvijek nije dovoljno istražen. U ovom se radu analiziran je utjecaj homogenata trutovskog legla (DBH) u prehrani nazimica na folikulogenezu. Ženke pasmine veliki jorkšir u dobi od 35 dana nasumično su podijeljene u dvije skupine po 10 životinja, s jednakim osnovnim prehrambenim obrokom. Pokusnoj skupini u krmu je dodavano 25 mg/kg DBH-a tijekom 180 dana, nakon čega su životinje usmrćene te je učinjena morfometrijska, histološka i imunohistokemijska procjena jajnika. Zatim je u oocitama i stanicama kumulusa RT-PCR-om analiziran izražaj faktora rasta jajnika, BMP15 i GDF9. U skupini s dodatkom prehrani DBH ustanovljen je znakovit porast tjelesne mase i prosječnog dnevnog prinosa 145. dan. Povećana je i dužina jajnika u pokusnih životinja. U životinja hranjenih dodatkom pronađeno je više nakupina primordijalnih folikula uključenih u intenzivan rast, kao i veći promjer primarnih i tercijarnih folikula. Ovi su rezultati u skladu s porastom izražaja GDF9 mRNA u oocitama i stanicama kumulusa. Istodobno su opaženi znakovi atrezije u Graafovim folikulima pokusnih životinja. Dodatak prehrani DBH stimulira rane stadije folikulogeneze u nazimica, ali uzrokuje atreziju u posljednjem stadiju folikularnog razvoja.

Calcium plays a role of universal cellular regulator in the living cell and one of the crucial regulators of proper fetal development during gestation. Mitochondria are important for intracellular calcium handling and signaling. Mitochondrial calcium uniporter (mtCU) is a multiprotein complex of the mitochondrial inner membrane responsible for the transport of calcium to the mitochondrial matrix. In the present study, we analyzed the expression level of mtCU components in two parts of the feto-maternal system – placenta and myometrium at full-term delivery and at preterm birth (PTB) on different stages: 22–27, 28–32, 33–36 weeks of gestation (n = 50). A gradual increase of mRNA expression and changes in protein content of MCU and MICU1 subunits were revealed in the placenta during gestation. We also observed slower depolarization rate of isolated placental mitochondria induced by Ca2+ titration at PTB. In myometrium at PTB relative gene expression level of MCU, MCUb and SMDT1 increased as compared to full-term pregnancy, but the tendency to gradual increase of MCU protein simultaneous with MCUb increase and MICU1 decline was shown in gestational dynamics. Changes observed in the present study might be considered both natural dynamics as well as possible pathological mechanisms underlying preterm birth.

Relevance: Mitochondrial dysfunction and systemic inflammation are believed to play pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) and related complications of metabolic disorders in adult patients. Though such researches are limited or almost absent in adolescents. The aim of the study is to evaluate the impact of mitochondrial dysfunction and systemic inflammation on PCOS pathogenesis during adolescence with regard to body mass index and insulin resistance. Design: a case-control study. Methods: The study included 95 adolescent girls (15 to 17 years old inclusive) diagnosed with PCOS based on the Rotterdam criteria. The control group consisted of 30 healthy girls of the same age with a regular menstrual cycle. All participants were subjected to a full clinical and instrumental examination, as well as an assessment of the levels of leptin, C-reactive protein (CRP), and malondialdehyde (MDA) as oxidative stress marker. Serum levels of IL-6, IL-10, IL-18, TNF-&alpha, and plasma concentrations of macrophage migration inhibitory factor (MIF), sFas, and sFasL were determined. Patients with PCOS were divided into groups according to the presence of metabolic disorders (MD) (impaired glucose tolerance and/or over insulin resistance) and normal weight or excessive weight (NW or OW). Results: Patients with PCOS of NW in the absence of metabolic disorders (MD&minus, /NW) had a lower concentration of MDA and a higher level of IL-10 compared to healthy girls (p &lt, 0.05). The group (MD&minus, /NW) was characterized with lower levels of CRP, leptin, MDA, and higher levels of sFasL, when compared to OW patients with PCOS in the absence of metabolic disorders (MD&minus, /OW) (p &lt, 0.05). Overweight adolescent girls with PCOS and metabolic disorders (MD+/OW) showed higher CRP, leptin, and a two-fold increase in IL-6 and IL-18 concentrations compared to the control group of healthy girls (p &lt, 0.05 for all parameters). The group (MD+/OW) was also characterized with higher levels of CRP, leptin, MDA, IL-18, MIF (p &lt, 0.05), when compared to overweight patients with PCOS in the absence of metabolic disorders (MD&minus, /NW). In comparison with the MD&minus, /OW group, the obese insulin resistant girls with PCOS (MD+/OW) had a highera level of IL-18 (p &lt, 0.05). Moreover, the MD+/OW girls demonstrated a significant increase in CRP, MDA and IL-18 levels when compared to the MD+/NW group (p &lt, 0.05). OW girls with PCOS without MD (MD&minus, /OW) had lower concentrations of sFasL compared to healthy girls (p &lt, 0.05), and higher levels of MDA compared to MD+/NW (p &lt, 0.05). Adolescent girls of NW with PCOS and with MD (MD+/NW) had lower levels of MDA compared to the control group of healthy girls (p &lt, 0.05). These data are confirmed by a correlation analysis and two-factor ANOVA test. Conclusions: Lean girls with PCOS demonstrate the protective mechanism of decrease in oxidative stress mediated by the activation of antioxidant defense, reduction of lipid peroxidation and systemic inflammation. Excessive weight and metabolic disorders in adolescents with PCOS are the most significant factors in reducing the capacity of antioxidant systems, activation of oxidative stress, mitochondrial dysfunction, and systemic inflammation.