Chronic low-grade inflammation has been suggested as a key contributor of the pathogenesis and development of polycystic ovary syndrome (PCOS). To investigate the association between oxidative stress status and inflammatory cytokines in follicular fluid of 21 PCOS women compared to 21 women with normal ovarian function who underwent intra-cytoplasmic sperm injection. Concentration of IL-6, IL-8, IL-10, and TNF-α was measured using sandwich ELISA. Oxidative stress was examined by measuring total oxidant status (TOS), malondialdehyde (MDA), total antioxidant capacity (TAC), and thiol groups. PCOS women had an elevated concentration of MDA and TOS compared to controls. Levels of TAC and thiol groups were lower in PCOS compared to controls. PCOS patients had a higher concentration of IL-6, IL-8, and TNF-α compared to controls. Concentration of IL-10 was lower in PCOS compared to controls. Significant correlations were found between MDA and TOS concentration with TNF-α and between IL-6 and MDA, IL-8 and TAC, IL-10 and TOS levels and also between IL-10 and TAC levels. TAC and thiol groups were negatively correlated with TNF-α. Increased oxidative stress in PCOS is associated with inflammation which is closely linked. Inflammation can induce production of inflammatory cytokines in this syndrome and directly stimulates excess ovarian androgen production.
Unexplained recurrent spontaneous abortion (RSA) might be caused by the mother's immunological rejection of the fetus. In this cross-sectional study, the percentage of T helper 17 (Th17), T regulatory (Treg) cells and their cytokines as the main players of immunomodulation in peripheral blood lymphocytes during the luteal phase of 20 women with unexplained RSA were compared with 20 normal non-pregnant women. The percentage of Treg cells in the former was significantly lower compared with controls. The percentage of Th17 cells in the former was higher than controls. Expression of IL-23, IL-17, IL-6 cytokines in the former was significantly higher than controls, but the higher expression of IL-21 was not significant. The gene expression of TGF-β and FoxP3 in the former was lower than controls. Significant positive correlations were found between the percentage of Th17 cells with IL-23, IL-6 and IL-17 and between expression of IL-23 and IL-6 and IL-17. IL-6 gene expression showed a significant positive correlation with IL-17. Therefore, imbalance of Th17-Treg cells and the consequent changes in cytokine expression might be implicated in the pathogenesis of unexplained RSA and may provide new insight into the immunoregulatory events at the maternal-fetal interface.
The Acp2 gene encodes lysosomal acid phosphatase 2 (ACP2), an isoenzyme that hydrolyzes orthophosphoric monoesters to alcohol and phosphate. Mutations in this gene compromise lysosomal function and cause acid phosphatase deficiency. Loss of Acp2 in the brain causes defects in the cerebellum. Here, we performed an in-depth protein expression analysis in the mouse cerebellum to understand how Acp2 controls cellular function in the developing and adult brain. We have found that during development, ACP2 expression marks the caudal midbrain and cerebellum, two regions that are linked by multiple signaling mechanisms during embryogenesis. By around P8, ACP2 was localized predominantly to the somata of Purkinje cells, the principal neurons of the cerebellar cortex. During the second postnatal week, we found that ACP2 expression expanded into the dendrites and axon terminals of Purkinje cells. However, at 2 weeks of age, only a subset of Purkinje cells strongly express ACP2. Further expression analyses revealed that in the mature cerebellum, ACP2 expression divided Purkinje cells into a pattern of molecular zones that are associated with the functional topography of sensory-motor circuitry. These data suggest that ACP2 expression is dynamically regulated during development, and in the adult, it may function within a complex architecture that is linked to cerebellar modular organization.
We evaluated gene expression of estrogen and progesterone nuclear receptors in granulosa cells (GCs) of polycystic ovary syndrome (PCOS) women compared to women with normal cycling ovaries (control group) to achieve a better understanding of ovarian steroid status in patients with PCOS. In this prospective study, 40 patients with PCOS and 40 women with normal ovulatory function who underwent in vitro fertilization (IVF) for treatment of tubal and/or male infertility were recruited. Follicular fluid was collected from patients and GCs were isolated from follicular fluid and then were purified with Micro Beads conjugated to monoclonal anti-human CD45 antibodies. RNA was extracted and reverse transcription was performed. Gene expression of estrogen and progesterone receptors was determined by quantitative real time PCR (qRT-PCR). Estrogen receptor β (ERβ) expression was significantly higher than ERα expression in both groups (p < 0.002). ERα and ERβ mRNA expression in PCOS was significantly lower than control group (p < 0.002). The expression levels of PRA and PRB in PCOS was significantly lower than control group (p < 0.002). In conclusion, a significant reduction of these genes in GCs from follicles of women with PCOS could be considered as a sign for maturation defect or follicular arrest in GCs.
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