ABSTRACT
PCOS is one of the most common endocrine disorders affecting women and it is characterized by a combination of hyper-androgenism, chronic anovulation, and insulin resistance. While a significant progress has recently been made in the diagnosis for PCOS, the optimal infertility treatment remains to be determined. Two inositol isomers, myo-inositol (MI) and D-chiro-inositol (DCI) have been proven to be effective in PCOS treatment, by improving insulin resistance, serum androgen levels and many features of the metabolic syndrome. However, DCI alone, mostly when it is administered at high dosage, negatively affects oocyte quality, whereas the association MI/DCI, in a combination reproducing the plasma physiological ratio (40:1), represents a promising alternative in achieving better clinical results, by counteracting PCOS at both systemic and ovary level.
Subject(s)
Inositol/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Vitamin B Complex/therapeutic use , Androgens/blood , Animals , Drug Therapy, Combination , Female , Humans , Inositol/administration & dosage , Inositol/chemistry , Insulin Resistance , Oocytes/metabolism , Polycystic Ovary Syndrome/physiopathology , Stereoisomerism , Vitamin B Complex/administration & dosage , Vitamin B Complex/chemistryABSTRACT
PURPOSE: To examine changes in the ratio of Bax and Bcl-2 mRNA expression throughout the ovulatory cycle in the ampullary region of the human oviduct. METHODS: The mucosal layer was isolated from the human oviduct tissue and semiquantitative reverse-transcriptase polymerase chain-reaction (RT-PCR) analysis of mRNA of Bax and Bcl-2 was performed. Immunohistochemistry provided the cellular localization of the Bax and Bcl-2 proteins. The ratio of expression of Bax and Bcl-2 mRNA was examined in the ampullary region of the oviduct in samples obtained in the follicular, periovulatory, and luteal phases of the ovulatory cycle. RESULTS: Bax expression was constant in the follicular and periovulatory phase but showed a significant increase in the luteal phase. The Bax protein was present in all oviduct mucosal epithelial cells and the intensity of staining increased in luteal phase samples. Bcl-2 was expressed at a relatively constant level throughout the ovulatory cycle. The Bcl-2 protein was present in some but not all mucosal epithelial cells and the proportion of positive cells remained constant throughout the ovulatory cycle. CONCLUSION: The proapoptotic gene Bax shows a significant increase in mRNA expression in the luteal phase of the ovulatory cycle while the expression level of the antiapoptotic gene Bcl-2 remains constant throughout the ovulatory cycle. The ratio of Bax:Bcl-2 increases significantly in the luteal phase consistent with cells undergoing apoptosis.
Subject(s)
Fallopian Tubes/metabolism , Gene Expression Regulation , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/biosynthesis , bcl-2-Associated X Protein/metabolism , Apoptosis , Female , Humans , Immunohistochemistry , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
UNLABELLED: The ratio of the active progesterone receptor B isoform is higher in the ampullary region of the oviduct. PURPOSE: To examine mRNA expression of progesterone receptor isoforms AB and B in oviduct mucosal tissue during the ovulatory cycle and in the different functional regions of the human oviduct. METHODS: The mucosal layer was isolated from human oviduct tissue and semi-quantitative RT-PCR for progesterone isoforms AB and B was performed. The RT-PCR results were verified by immunohistochemistry. RESULTS: The isthmic region showed no mRNA expression of either progesterone receptor isoform while the relative ratio of the B isoform was significantly higher in the ampullary region compared to the fimbrial region. There was a significant increase in the ratio of PRB to PRAB in the ampullary region compared to the fimbrial region in all samples. CONCLUSIONS: We found an increase in the relative abundance of the progesterone receptor B isoform in the ampullary region which is the site of fertilization and early embryo cleavage. Our results indicate that progesterone responsive genes are more likely to be activated in the ampullary region of the oviduct due to the difference in PRAB to PRB ratio. Providing support for the hypothesis that progesterone may play a specific role in providing an appropriate environment for sperm capacitation, fertilization and early embryo cleavage.
Subject(s)
Fallopian Tubes/metabolism , Follicular Phase , Ovulation/physiology , Receptors, Progesterone/metabolism , Fallopian Tubes/cytology , Female , Humans , Mucous Membrane/metabolism , RNA, Messenger/metabolismABSTRACT
BACKGROUND: The follicular microenvironment is an important determinant of oocyte development. The aim of this study was to examine whether the myo-inositol (MI) content in human follicular fluid (FF) was associated with better oocyte quality. METHODS: A total of 53 patients treated with IVF was recruited to a prospective observational study. FF and serum samples collected were divided into two groups: group A consisted of FF associated with matured and fertilized oocytes, whilst group B was from follicles with immature and unfertilized oocytes. RESULTS: Patient's age, total ampoules of HMG used, days of stimulation, basal levels of FSH, estradiol (E(2)) levels on the day of HCG, and serum MI content were not significantly different between the two groups. FF volume and its MI content were significantly higher in group A compared with group B (P < 0.05). The levels of MI in FF were positively correlated with the amount of E(2) in their corresponding FF samples and also correlated with embryo quality. CONCLUSIONS: We propose that higher concentrations of MI and E(2) in human FF appear to play a role in follicular maturity and provide a marker of good quality oocytes.
