heparitin-sulfate and Infertility--Female

The aim of this study was to quantify the sulfated glycosaminoglycans in the endometria of women with polycystic ovary syndrome (PCOS). Of the 18 patients recruited for this study, 10 patients with PCOS comprised the PCOS group (PCOSG), and eight patients with regular and ovulatory menstrual cycles comprised the control group (CG). The clinical, biochemical, morphological and endometrial data from both groups were analyzed. Biopsies were performed during the proliferative phase of the menstrual cycle for the CG and during the persistent proliferative phase for the PCOSG (all women were amenorrheic). In the PCOSG, there was a significant increase in the endometrial concentration levels of heparan sulfate (p = 0.03), but no difference in the concentrations of chondroitin sulfate was determined between the two groups (p = 0.77). Period of time without menstruation (p = 0.001) and body mass index (BMI) (p = 0.04) correlated directly and positively with heparan sulfate concentration. There was no association between heparan sulfate levels and basal insulin values (p = 0.08). High levels of endometrial heparan sulfate in women with PCOS indicate an interference with maternal-fetal recognition, which contributes to infertility; thus, endometrial heparan sulfate may be a predictive marker of future neoplasia risk.

Topics: Adult; Biomarkers; Biopsy; Body Mass Index; Brazil; Chondroitin Sulfates; Endometrial Neoplasms; Endometrium; Female; Follicular Phase; Heparitin Sulfate; Hospitals, University; Humans; Infertility, Female; Outpatient Clinics, Hospital; Overweight; Polycystic Ovary Syndrome; Risk; Up-Regulation; Young Adult

Although it was suggested that heparanase (HPSE) may affect implantation and pregnancy, so far there have been no wide-ranging studies on the expression of and possible disturbances in the interactions between HPSE, heparan sulfate (HS) and related growth factors, such as heparin-binding EGF-like growth factor (HB-EGF). The aim of this study was to evaluate whether the expression profile of both HPSE and HB-EGF can be associated with impaired reproduction in the endometrial implantation window, in the non-conception cycle. The study group consisted of 32 women with two or more unexplained, consecutive miscarriages, and 61 idiopathic infertility patients, while the control comprised of 22 women with normal reproductive potential. We compared the expression of HB-EGF and HPSE at the transcript (qPCR) and protein (Western Blot) levels in eutopic endometrium. Also assessed were correlations between both factors in the studied groups. In women with consecutive miscarriages we observed lower HPSE relative transcript (p = 0.003) and lower protein (p = 0.002) level compared with the control group. Level of the HB-EGF protein was decreased (p = 0.017). HPSE mRNA level was higher in idiopathic infertility (p = 0.003) compared with women with miscarriages. We found statistically significant correlations in both transcript and protein levels in all groups (p < 0.05). Our results allow the assumption of the existence of a process by which, in normal human endometrium, HB-EGF expression coincides with the synthesis of HPSE. As a result, the HB-EGF molecule can bind to the HS on the cell surface, enhancing its affinity to the receptor. Then, the release of growth factors associated with HS oligomers occurs that is catalyzed by HPSE. We suggest that one of the causes of unexplained miscarriages may result from the impaired expression of HPSE and HB-EGF.

Topics: Abortion, Habitual; Adult; Case-Control Studies; Embryo Implantation; Endometrium; Female; Glucuronidase; Heparin-binding EGF-like Growth Factor; Heparitin Sulfate; Humans; Infertility, Female; Intercellular Signaling Peptides and Proteins; Menstrual Cycle; Pregnancy; RNA, Messenger; Transcription, Genetic