Beneficial effects of metformin on mice female fertility after a high-fat diet intake.

Female fertility is highly dependent on energy balance. High fat diet (HFD) intake entails a risk of infertility and ovulatory disorders. Considering the increase in the prevalence of overweight and obesity over the last decades, it is crucial to understand the mechanisms involved in overweight-associated infertility. In this study, we evaluated the reproductive performance of female mice fed with a HFD and the effects of metformin administration on ovarian function in these mice. We hypothesized that one of the mechanisms involved in subfertility due to a HFD intake is the alteration of ovarian blood vessel formation. We found that mice fed with HFD had altered estrous cycles and steroidogenesis, increased ovarian fibrosis, fewer pups per litter and require more time to achieve pregnancy. HFD-fed mice also presented dysregulated ovarian angiogenesis and an increase in nuclear DNA damage in ovarian cells. Ovulation rates were lower in these animals, as evidenced both in natural mating and after ovulation induction with gonadotropins. Metformin ameliorated ovarian angiogenesis, improved steroidogenesis, fibrosis, and ovulation, decreased the time to pregnancy and increased litter sizes in HFD-fed mice. We conclude that ovarian angiogenesis is one of the mechanisms detrimentally affected by HFD intake. Since metformin could improve ovarian microvasculature, it may be an interesting strategy to study in women to shed light on new targets for patients with metabolic disturbances.

Longitudinal Study after Sputnik V Vaccination Shows Durable SARS-CoV-2 Neutralizing Antibodies and Reduced Viral Variant Escape to Neutralization over Time.

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic. However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.