PCOS is a reproductive hormonal abnormality and a metabolic disorder. It is frequently associated with insulin resistance, hyperandrogenism, chronic inflammation, and oxidative stress. We aim to investigate the potential therapeutic effects of combined therapy of resveratrol and metformin on polycystic ovaries via SIRT1 and AMPK activation. Wistar albino rats were divided into control and experimental (PCOS) groups. DHEA-induced PCOS rats were given resveratrol (20 mg/kg/day), metformin (300 mg/kg/day) and combined therapy. At the end of the experiment, the body and ovarian weight of rats were measured and blood samples were analyzed for FSH, LH, testosterone, AMH, TNF-α and MDA levels. Histopathological evaluation of ovaries were carried out by light and electron microscopy. SIRT1 and AMPK immunreactivity and TUNEL assay were scored. Data were statistically analyzed by SPSS programme. Metformin and combined treatment groups reduced the body and ovary weights compared to the PCOS group. Serum testosterone levels were significantly higher in the PCOS group than in the control group and this was reduced when PCOS was treated with all but especially resveratrol. All the treatment groups decreased LH, LH/FSH, TNF-α and tissue AMH levels which were induced in the PCOS group, whereas metformin was unable to improve the increased MDA and plasma AMH levels. Treatment with resveratrol and/or metformin ameliorated the elevated number of secondary and atretic follicles and the decreased number of Graafian follicles in the PCOS group, which indicates the effect of the treatments on the maintenance of folliculogenesis. Light and electron microscopic findings supported the analysis of follicular count. Increased number of TUNEL (+) granulosa cells in the PCOS group were reduced significantly in the treatment groups. Resveratrol and metformin increased SIRT1 and AMPK immunreactivity, respectively, compared to the PCOS group. The results suggest that combined therapy of metformin and resveratrol may improve the weight gain, hormone profile and ovarian follicular cell architecture by inducing antioxidant and antiinflammatory systems via SIRT1 and AMPK activation in PCOS.

Type 2 diabetes (T2DM) is one of the most serious challenges of the 21th century with life-threatening complications and excessive health care costs. In diabetic patients, the main goal in T2DM treatment is the regulation of both blood glucose and lipid levels. For that, Gliclazide (GLZ), an oral antidiabetic, and Atorvastatin (ATV), a lipid lowering agent, are widely used drugs as combination. Diabetes has been reported severe impacts on male reproductive system; however, data obtained about ATV and GLZ treatment alone or in combination are conflicted or insufficient. Herein the effects of ATV and GLZ on male reproductive system in type 2 diabetic male rats have been investigated in the present study. T2DM was induced by high-fat diet and single injection of streptozotocin (STZ) (35 mg/kg) in young adult male Sprague-Dawley rats. The diabetic rats were given ATV (10 mg/kg), GLZ (10 mg/kg) and ATV/GLZ (1:1, 10 mg/kg) combination by oral gavage for 28 days. The hormone levels were determined in the cardiac blood samples; and the histopathological and ultrastructural analyses were conducted in the testicular tissues and epididymal sperms. It was observed that diabetes had severe effects on testicular tissue and spermatogenesis. ATV treatment did not affect sperm count and testes structure (p > 0.05), however ameliorated sperm morphology (p < 0.05). GLZ treatment increased sperm count, and improved sperm morphology, testes structure and spermatogenesis (p < 0.05). ATV/GLZ combination treatment enhanced sperm morphology and improved testicular structure (p < 0.05) while did not affect sperm count (p > 0.05). GLZ treatment regenerated testicular damage and sperm parameters whether alone or in combination with ATV in diabetic rats without affecting hypothalamic-pituitary-gonadal axis.

Background and Objectives: Bone and mineral disease (BMD) is a prevalent complication of advanced chronic kidney disease (CKD). The risk of fractures can be assessed via dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). This study aims to evaluate the effectiveness of two imaging modalities in identifying bone mineral status in individuals with pre-dialysis chronic renal disease and to assess their correlation with bone turnover markers. Materials and Methods: This controlled cross-sectional study, conducted at a single center from 2019 to 2022, assessed two groups of individuals aged 18 to 50. The patient cohort consisted of individuals with stage 4–5 chronic kidney disease, whereas the control cohort consisted of healthy participants. The participants’ bone and mineral status was evaluated using both QCT and DXA methods. Diagnostic measurements of the lumbar spine and femoral neck, obtained using DXA and QCT, were compared. Z-scores were utilized to evaluate low bone mineral density, with low Z-scores identified in either lumbar spine or femoral neck measures being seen as indicative of low bone mineral density. Results: Data from 38 participants (patient group: 18; control group: 20) who underwent QCT and/or DXA were evaluated. Thirty-three subjects were assessed using both QCT and DXA (patient group: 14; control group: 19). The median age of the patient cohort was 44 (range: 22–50), whereas the median age of the control cohort was 42 (range: 27–48) (p = 0.72). Women constituted 33% of the patient cohort and 50% of the control cohort (p = 0.23). In the patient cohort, low bone mineral density was detected in four individuals (28%) through QCT, and in just two patients (14%) through DXA. Compared to DXA, QCT identified a higher number of cases of low bone mineral density in the CKD cohort; however, no statistically significant difference was observed (p = 0.06). In addition, our study found that TRACP5b had a strong negative correlation with the DXA L1–L4 Z-score. Conclusions: This study revealed that QCT may be more sensitive than DXA for detecting low bone density in pre-dialysis CKD patients. Additionally, DXA may overestimate lumbar spine BMD in this population, and the strong negative correlation between TRACP5b levels and the DXA L1–L4 Z-score highlights the potential role of biochemical markers in assessing bone status in CKD

Sperm chromatin integrity is essential for successful fertilization and normal embryo development; however, a substantial proportion of infertile men exhibit abnormalities in sperm chromatin structure. Recent studies have shown that exosomes isolated from the conditioned medium of adipose tissue–derived mesenchymal stem cells may improve sperm chromatin abnormality following in vitro incubation, highlighting the potential of exosome-mediated mechanisms. Heat shock protein A2 (HSPA2) is a key regulator of genome remodeling during sperm chromatin maturation and has been identified in both the mouse endometrium and avian uterosomes. Accordingly, this study investigates whether human endometrial cell–conditioned medium (EC-CM) containing uterosomes (endometrium-derived exosomes) can improve sperm quality by targeting chromatin abnormalities. This study aimed to evaluate the presence of HSPA2 within uterosomes and, if present, to explore whether the transfer of uterosomal HSPA2 to sperm contributes to sperm chromatin remodeling. Our findings indicate that EC-CM contains uterosomes with HSPA2, and incubation of sperm with abnormal chromatin structure with EC-CM is associated with improved chromatin abnormality. These results suggest that bioactive molecules released by endometrial cells may contribute to the modulation of sperm chromatin quality and highlight a potential role in improving sperm function prior to assisted reproductive technologies.