Obesity and Male Reproduction: Do Sirtuins Play a Role?

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer. SIRTs regulate the energy balance, the lipid balance, glucose metabolism, and adipogenesis, but current evidence also indicates a role for SIRTs in male reproduction. However, the majority of the studies have been conducted in animal models and very few have been conducted with humans. This review shows that SIRTs play an important role among the molecular mechanisms by which obesity interferes with male fertility. This highlights the need to deepen this relationship. It will be of particular interest to evaluate whether synthetic and/or natural compounds capable of modifying the activity of SIRTs may also be useful for the treatment of obesity and its effects on gonadal function. Although few studies have explored the role of SIRT activators in obesity-induced male infertility, some molecules, such as resveratrol, appear to be effective in modulating SIRT activity, as well as counteracting the negative effects of obesity on male fertility. The search for strategies to improve male reproductive function in overweight/obese patients is a challenge and understanding the role of SIRTs and their activators may open new interesting scenarios in the coming years.

Cytoplasmic incompatibility in the semivoltine longicorn beetle Acalolepta fraudatrix (Coleoptera: Cerambycidae) double infected with Wolbachia

Wolbachia are obligatory endosymbiotic α-proteobacteria found in many arthropods. They are maternally inherited, and can induce reproductive alterations in the hosts. Despite considerable recent progress in studies on the associations between Wolbachia and various taxonomic groups of insects, none of the researches have revealed the effects of Wolbachia on longicorn beetles as the host insect. Acalolepta fraudatrix is a forest longicorn beetle that is distributed in East Asia. In this study, the relationship between Wolbachia and A. fraudatrix was investigated. Out of two populations of A. fraudatrix screened for Wolbachia using the genes ftsZ, wsp, and 16S rRNA, only one of the populations showed detection of all three genes indicating the presence of Wolbachia. Electron microscopy and fluorescent in situ hybridization also confirmed that the A. fraudatrix population was infected with Wolbachia. Sequencing the wsp genes derived from single insects revealed that two strains of Wolbachia coexisted in the insects based on the detection of two different sequences of the wsp gene. We designated these strains as wFra1 and wFra2. The bacterial titers of wFra1 were nearly 2-fold and 3-fold higher than wFra2 in the testes and ovaries, respectively. The two strains of Wolbachia in the insects were completely eliminated by rearing the insects on artificial diets containing 1% concentration of tetracycline for 1 generation. Reciprocal crosses between Wolbachia-infected and Wolbachia-uninfected A. fraudatrix demonstrated that only eggs produced by the crosses between Wolbachia-infected males and Wolbachia-uninfected females did not hatch, indicating that Wolbachia infecting A. fraudatrix causes cytoplasmic incompatibility in the host insect. This is the first report showing the effect of Wolbachia on reproductive function in a longicorn beetle, A. fraudatrix.

Depression in postmenopause: interdisciplinary approach in management and perspectives for rehabilitation

Surgical and natural menopause is often associated with depression symptoms. Along with the postpartum period, perimenopause is a “window of vulnerability” for depression development, because decline in estrogen level accounts for extinction of reproductive function, emotional disorders, genitourinary menopausal syndrome, which are combined with non-endocrine risk factors, such as decreasing income levels, low social support, and stress. Although a direct relationship between blood estrogens level and depression has not been demonstrated, the relation between menopause symptoms and depression has been proven, i.e., the symptoms of menopause can be considered as risk factors. Here, we summarizes the current view on the correct counseling and routing of menopausal women with depression symptoms in primary health care facilities, the principles of managing patients with risk factors, including genitourinary menopausal syndrome, as well as methods of rehabilitation and informational support. This will aid to improve the quality of medical care for such patients.

Food status enhancement product and improving human reproductive function

Охрана репродуктивного здоровья предполагает множество направлений деятельности, в том числе мероприятия, направленные на коррекцию пищевого статуса мужчин и женщин репродуктивного возраста, особенно беременных и кормящих женщин. Объектом исследований являлся паштет печеночный профилактической и лечебной направленности с включением пищевой системы на основе альбумина пищевого, жмыха зародышей пшеницы и фасоли. Исследованы органолептические, функционально-технологические, реологические показатели качества и безопасности, микроструктура паштета, обоснованы параметры и режимы подготовки пищевой системы и готового изделия с ее применением. Установлено, что массовая доля таких нутриентов, как Fe, Zn, Na, P и водорастворимых витаминов (В и В), находилась на уровне 20 % и более от суточной потребности. Отмечено увеличение содержания в диапазоне от 20 до 50 % суточной потребности фолиевой кислоты, витаминов В, В, С и D, что позволяет отнести разработанный паштет к функциональному продукту. При этом содержание некоторых компонентов (Mn, Cu, витаминов В, В) превысило уровень 50 % суточной потребности, благодаря чему паштет также можно отнести к витаминизированным продуктам. Выявлено улучшение сбалансированности состава полиненасыщенных жирных кислот, в разработанном продукте соотношение омега-6 к омега-3 кислот соответствовало рекомендациям НИИ питания РАМН (5-10:1) и составляло соответственно (омега-6 : омега-3) 7:1. Биологическая ценность спроектированного паштета находится на высоком уровне и достигает значения 69,8 %, показатель КРАС 30,2 %, что свидетельствует о незначительном количестве избыточных аминокислот в белковой фракции продукта. The protection of reproductive health involves many areas of activity, including measures aimed at correcting the nutritional status of men and women of reproductive age, especially pregnant and lactating women. The object of research was liver pate of preventive and therapeutic orientation with the inclusion of a food system based on food albumin, wheat germ cake and beans. Organoleptic, functional-technological, rheological, quality and safety indicators, the microstructure of the pate are studied, the parameters and modes of preparation of the food system and the finished product with its use are justified. It was found that the mass fraction of nutrients such as iron, zinc, H, P and water-soluble vitamins (B and B) was at the level of 20 % or more of the daily requirement. There was an increase in the content of folic acid, vitamins B, B, C and D in the range from 20 to 50% of the daily requirement, which allows us to attribute the developed pate to a functional product. At the same time, the content of some components (manganese, copper, vitamins B, B) exceeded the level of 50 % of the daily requirement, so that the pate can also be attributed to fortified products. An improvement in the balance of the composition of polyunsaturated fatty acids was revealed, the ratio of omega-6 to omega-3 acids in the developed product corresponded to the recommendations of the Research Institute of Nutrition of the Russian Academy of Medical Sciences (5-10:1) and was respectively (omega-6 : omega-3) 7:1. The biological value of the designed pate is at a high level and reaches a value of 69.8 %, the RED indicator (30.2 %), which indicates an insignificant amount of excess amino acids in the protein fraction of the product.

Analysis of the results of epizootic monitoring of viral diarrhea — a disease of mucous membranes in cattle in the Russian Federation according to the reporting of 4-vet for 2020

Relevance. The reproductive health of dairy cows is one of the top priorities in dairy farming. Viral diarrhea, a disease of mucous membranes in cattle, is one of the causes of impaired reproductive function on farms. The disease is widespread throughout the world and causes significant economic damage, which consists of a decrease in productivity, lack of offspring, impaired reproductive function of the broodstock, costs of treatment and specific prevention. The viral diarrhea virus has an immunosuppressive effect. Diagnosis is complicated by a “blurry” clinical picture due to the association of the virus with other respiratory-intestinal viruses and the addition of a secondary bacterial infection, as well as the presence of a persistent form of infection. The diagnosis requires the analysis of clinical and epizootic data, pathological changes and a combination of several methods of laboratory diagnostics. An important link in the prevention and recovery of herds is the conduct of epizootic monitoring and analysis of its results.Methodology. The assessment of the epizootic situation for viral diarrhea, a disease of mucous membranes in cattle in the Russian Federation for 2020, was carried out based on the results of the analysis of information obtained from annual reports provided by state veterinary laboratories in the FSBI CNMVL in the form of 4-vet (annual).Results. Based on the results of the epizootic monitoring, it can be concluded that the viral diarrhea virus is widely circulating in the livestock farms of the Russian Federation. In 2020, positive results were recorded in all federal districts of the Russian Federation (in 33 subjects), except for the Far Eastern Federal District. The most difficult epizootic situation is in the North Caucasus Federal District and the Central Federal District (38% and 29% of the total number of positive results, respectively).

Diagnostic markers of human papillomavirus persistence and progression of cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia is widespread among patients of the reproductive period, the peak of the incidence occurs at a young age, often when the reproductive function has not yet been performed. The oncological alertness of the medical community is justified: the incidence of cervical cancer has increased by 24.6% over the past ten years, and in the structure of cancer mortality in the age group of 30–39 years cervical cancer occupies the 1st place accounting for 23%. Тhe same time aggressive management of the disease in patients who have not yet performed their reproductive function is associated with the loss of significant volume of cervical tissues and an increase in the frequency of premature birth. The most acute issue is the tactics of managing cervical neoplasia of the second degree of severity, when there is still hope for the regression of the disease, but at the same time there is a high risk of transition to dysplasia of the third degree of severity and subsequently to invasive cancer. The search for diagnostic markers that allow predicting the probability of regression and, conversely, the unfavorable course of the disease is the most important task solution of which will allow optimizing tactics in controversial clinical cases and avoiding unnecessary surgical aggression, improving the perinatal outcomes of patients undergoing surgical treatment. The search for new economically feasible and diagnostically valuable markers allowing us to predict the course of the disease and determine the amount of necessary surgical treatment continues, but the most significant at this moment is still the determination of the coexpression of p16 and Ki-67 in immunocytochemical studies and p16INK4a in immunohistochemical studies. The diagnostic sensitivity of determining the co-expression of p16INK4a/Ki67 is 98.5%, and the expression of p16INK4a in CIN II indicates that in 81% of cases there is a tendency to a progressive course of the disease.

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

Background Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here, we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently, we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. Results Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. Conclusions SRD5A1/5α reductase-1 responds epigenetically to the environment and its downregulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs.

Normal Reproductive function in male mice lacking pituitary kisspeptin receptor.

The anterior pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate gonadal development, gametogenesis and the secretion of the gonadal steroid hormones. The gonadotroph is primarily regulated by hypothalamic secretion of gonadotropin-releasing hormone (GnRH) from neurons of the rostral hypothalamus and is mediated by GnRH receptor signaling. Kisspeptin (KISS1)/kisspeptin receptor (KISS1R) signaling in GnRH neurons plays an essential role in reproductive function. As the kisspeptin receptor is present in the pituitary, kisspeptin signaling via the Kiss1r may regulate reproductive function at the level of pituitary. Using Cre/Lox technology, we deleted the Kiss1r gene in pituitary gonadotropes (PKiRKO). PKiRKO male and females have normal genital development, puberty onset, and fertility. Females have normal LH, FSH and estradiol while males had significantly increased basal serum FSH levels with no differences in basal serum LH, or testosterone levels. Overall, these findings indicate that the pituitary KISS1R does not play a role in male reproduction.