Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy during women’s reproductive age. PCOS is a heterogeneous disorder featuring specific cardiometabolic properties. The association between the presence of metabolic disorders and PCOS supports the claim that the regulation of glycemic status is very important in these patients. There is a wide range of therapeutic options (including those treating diabetes mellitus type 2) with potential advantages available for the management of PCOS. Sodium–glucose cotransporter type 2 inhibitors (SGLT-2is) improve glucose metabolism, reduce fat tissue, lower blood pressure, reduce oxidative stress and inflammation, and protect the cardiovascular system. Currently, the use of SGLT-2is is not widespread in PCOS therapy, although these drugs represent a promising new therapeutic approach. Therefore, it is necessary to initiate further study in order to determine more effective therapies for PCOS and investigate the effect of SGLT-2is, both as a monotherapy and in combination with other drugs. It is necessary to understand the mechanisms underlying SGLT-2is in PCOS and their effects on long-term complications, especially since the gold standard treatment for PCOS, such as metformin and oral contraceptives, do not have long-term cardioprotective effects. The effects of SGLT-2is seem to involve cardiac protection, while diminishing endocrine and reproductive abnormalities in PCOS. In the current narrative review, we examine the most recent clinical evidence and discuss the potential applications of SGLT-2is for PCOS therapy.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.

Polycystic ovary syndrome (PCOS) is the most common complex endocrinological condition of women that is associated with infertility and metabolic disorders during the reproductive period. Recently, a great deal of research has focused on the etiopathogenesis of this disorder and the modulation of therapeutic approaches. There are still many controversies in the choice of therapy, and metformin is one of the most commonly used agents in the treatment of PCOS. Considering the link between metabolic disorders and PCOS, glycemic status is crucial in these patients, and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) represent a potentially promising new therapeutic approach. These drugs have been shown to improve glucose metabolism, reduce adipose tissue, decrease oxidative stress, and protect the cardiovascular system. These data prompted us to investigate the effects of empagliflozin (EMPA) in a PCOS rat model and compare them with the effects of metformin. We confirmed that EMPA positively affects somatometric parameters, glucose and lipid metabolism, and the levels of sex hormones, as well as reduces oxidative stress and improves ovarian function and morphology. Administration of EMPA at doses of 5 mg/kg, 15 mg/kg, and 45 mg/kg during a 4-week treatment period improved, as induced by estradiol valerate and a high-fat diet, the metabolic and reproductive statuses in a PCOS rat model. The best effects, which were comparable to the effects of metformin, were achieved in groups receiving the middle and highest applied doses of EMPA. These results may prompt further clinical research on the use of EMPA in patients with PCOS.

Innovative treatments for spinal muscular atrophy (SMA) yield the utmost advantages only within the presymptomatic phase, underlining the significance of newborn screening (NBS). We aimed to establish statewide NBS for SMA in Serbia. Our stepwise implementation process involved technical validation of a screening assay, collaboration with patient organizations and medical professionals, a feasibility study, and negotiation with public health representatives. Over 12,000 newborns were tested during the 17-month feasibility study, revealing two unrelated SMA infants and one older sibling. All three children received therapeutic interventions during the presymptomatic phase and have shown no signs of SMA. No false-negative results were found among the negative test results. As frontrunners in this field in Serbia, we established screening and diagnostic algorithms and follow-up protocols and raised awareness among stakeholders about the importance of early disease detection, leading to the incorporation of NBS for SMA into the national program on 15 September 2023. Since then, 54,393 newborns have been tested, identifying six SMA cases and enabling timely treatment. Our study demonstrates that effective collaborations between academia, non-profit organizations, and industry are crucial in bringing innovative healthcare initiatives to fruition, and highlights the potential of NBS to revolutionize healthcare outcomes for presymptomatic SMA infants and their families.

Background: The impact of the SARS-CoV-2 viral infection during pregnancy on the fetus can be direct—transmitted through the placenta—and indirect—creating unfavorable conditions for the development of the fetus because of inflammation, micro-thrombosis, and hypercoagulation. Our study aimed to determine the types and frequency of pathohistological changes in placental tissue in SARS-CoV-2-positive pregnant women and to examine the possible role of oxidative stress in the prognosis of the delivery and its maternal and fetal complications. Methods: This prospective clinical study included 50 pregnant women divided into two groups, SARS-CoV-2 positive (COVID-19 group) and SARS-CoV-2 negative (control group), from who we collected demographic, clinical, obstetric, biochemical and pathologic data. Data about the newborn characteristics were also collected, which included anamnestic, clinical, and biochemical data. Results: The values of the superoxide anion radical and index of lipid peroxidation were significantly different in mothers concerning the presence of the SARS-CoV-2 infection, while the levels of the nitric oxide, index of lipid peroxidation, reduced glutathione, and superoxide dismutase were significantly different in the newborns depending on the SARS-CoV-2 infection. Newborn characteristics were similar between groups except for concentrations of IgM antibody. The incidence of pathohistological changes of the FVM type in the COVID-19 group of pregnant women was 46%, while in the control group, the incidence was 18%. Conclusions: This study confirmed the significant impact of the SARS-CoV-2 viral infection on maternal and fetal biochemical parameters and oxidative stress-mediated placental dysfunction. Future studies should be performed with more participants and follow-up neonatal development.

SARS-CoV-2 has an affinity for binding to the human Angiotensin-converting enzyme 2 (ACE2) receptor through cleavage and conformational changes at the S1–S2 boundary and the receptor binding domain of the spike protein, which is also the most variable part of SARS-CoV-2. This study aimed to investigate the expression of Angiotensin-converting enzyme 2 (ACE2), spike protein, and CD68+ markers in placental tissue to demonstrate a possible correlation with the level of systemic oxidative stress biomarkers in patients who were infected with SARS-CoV-2 during pregnancy. A prospective clinical cohort study was designed to investigate the presence of CD68+ macrophages, ACE2, and spike proteins in placental tissue using immunohistochemical methods and to compare these results with oxidative stress from our previous study. Spike and CD68+ macrophages’ immunoreactivity were more pronounced in the placental tissue of patients from the SARS-CoV-2 group. Placental tissue spike protein and CD68+ immunoreactivity correlate with maternal and fetal Thiobarbituric Acid Reactive (TBARS) levels. This study has confirmed that spike protein expression in placental tissue is associated with the newborn’s stay in intensive neonatal care. Therefore, immunoreactivity analysis for the Spike antigen is important in detecting newborns at risk of early neonatal complications.