Reproductive Function Research Articles

The effect of norepinephrine on ovarian dysfunction by mediating ferroptosis in mice model.

Studies have shown that stress is associated with ovarian dysfunction. Norepinephrine (NE), a classic stress hormone involved in the stress response, is less recognized for its role in ovarian function. In this study, an NE-treated mouse model is induced by intraperitoneal injection of NE for 4 weeks. Compared with normal control mice, NE-treated mice show disturbances in the estrous cycle, decreased levels of anti-Mullerian hormone (AMH) and estradiol (E2), and increased level of follicle-stimulating hormone (FSH). Additionally, the numbers of primordial follicles, primary follicles, secondary follicles, and antral follicles are decreased, whereas the number of atretic follicles is increased in NE-treated mice, indicating NE-induced ovarian dysfunction. RNA sequencing further reveals that genes associated with ferroptosis are significantly enriched in NE-treated ovarian tissues. Concurrently, the levels of reactive oxygen species (ROS), ferrous ions, and malondialdehyde (MDA) are increased, whereas the expression level of glutathione peroxidase 4 (GPX4) is decreased. To elucidate the mechanism of NE-induced ferroptosis in ovaries and the potential reversal by Coenzyme Q10 (CoQ10), an antioxidant, we conduct both in vitro and in vivo experiments. In vitro, the granulosa cell line KGN, when treated with NE, shows decreased cell viability, reduced expression of GPX4, elevated levels of ferrous ion and ROS, and increased MDA level. However, these NE-induced changes are reversed by the addition of CoQ10. Compared with the NE group, the NE-treated mice supplemented with CoQ10 present increased GPX4 level and decreased iron, ROS, and MDA levels. Moreover, the differential expression of genes associated with ferroptosis induced by NE is ameliorated by CoQ10 in NE-treated mice. Additionally, CoQ10 improves ovarian function, as evidenced by increased ovarian weight, more regular estrous cycles, and an increase in follicles at various stages of growth in NE-treated mice. In conclusion, NE induces ovarian dysfunction by triggering ferroptosis in ovarian tissues, and CoQ10 represents a promising approach for protecting reproductive function by inhibiting ferroptosis.

Duration of efficacy and effect of implant location in adult queens treated with a 9.4 mg deslorelin subcutaneous implant

Deslorelin is a GnRH-agonist used off-label for contraception in female cats. Little is known about duration and safety of the 9.4 mg subcutaneous implant in the queen as well as its efficacy when placed periumbilically. Fourteen female cats were administered the 9.4 mg deslorelin implant (during interestrus or anestrus) either in interscapular (N=8) or periumbilical (N=6) sites, following general and reproductive examination, vaginal cytology, hematology, biochemistry and progesterone assay to ensure health status. All above procedures (except for progesterone assay) were repeated weekly during the first month, then every 2 months until 6 months and then every 6 months until treated cats regained full reproductive function. No side effects were observed in any treated queen. Post implantation estrus occurred in 40% of the subjects. A significant increase in body weight was observed during treatment (12/14 queens gained weight), particularly at the end of the study. At the end of the study some queens mated, conceived and kittened, proving reversibility of the treatment. The average duration of action of the 9.4 mg deslorelin implant was 790 +/- 155 days (range 525-1140 days) with no significant difference in duration or efficacy depending on implantation sites. The 9.4 mg deslorelin implant causes pharmacological sterilization for about 2 years in female cats, is fully reversible and caused no clinically relevant side effects when administered at both interscapular and periumbilical sites.

Mapping the Landscape of Obesity Effects on Male Reproductive Function: A Bibliometric Study.

Due to changes in lifestyle and dietary habits, the global population with obesity is increasing gradually, resulting in a significant rise in the number of individuals having obesity. Obesity is caused by an imbalance between energy intake and consumption, leading to excessive fat accumulation, which interferes with normal human metabolism. It is also associated with cardiovascular disease, metabolic syndrome, male reproductive endocrine regulation disorders, systemic and local inflammatory reactions, excessive oxidative stress, and apoptosis. All these factors can damage the internal environment for sperm generation and maturation, resulting in male sexual dysfunction, a decline in sperm quality, and lower fertility. This study analyzes the trends and priorities of the effects of obesity on male reproductive disorders from a bibliometric perspective. This study uses the Web of Science as the statistical source, covering all time spans. Tools like Web of Science, VOSviewer, and CiteSpace are used to analyze countries, institutions, authors, journals, and keywords in the field. Total publications, total citations, and average number of citations are selected for statistics. The results show that the research on the impact of obesity on male reproductive function can be roughly divided into three stages: the initial stage, the slow development stage, and the rapid development stage. Our statistical scope includes 463 highly relevant articles that we have screened. We found that the journal with the most publications in this field is Andrologia, and the institution with the highest total citations is the University of Utah. The most influential countries, institutions, and authors in this field are the United States, the University of Utah, and Carrell, Douglas. Currently, research related to the impact of obesity on male reproduction focuses mainly on three aspects: biochemistry, molecular biology, and reproductive biology. The keyword explosion results indicate that sperm, obesity, and male reproduction are at the forefront and trends of future research in this field. There has been a shift from basic biochemical and molecular research to research on molecular mechanisms relying on omics technologies. However, we have observed that the number of papers published in 2022 is lower than in 2021, indicating a growth interruption during this period. Considering that this deviation may be due to the impact of the COVID-19 pandemic, it may hinder the progress of certain experiments in 2022. In recent years, China has rapidly developed research in this field. However, the average citation rate is relatively low, indicating the need for Chinese scholars to improve the quality of their articles further. Based on our research and in the context of global obesity, men are at risk of increased infertility. Addressing this issue relies on our continued research into the mechanisms of obesity-related male reproductive disorders. Over the past forty-three years, with the contributions of scientists worldwide, research in this field has flourished. The impact of obesity on male reproductive disorders has been extensively studied. Currently, research in this field primarily focuses on male sperm function, sperm quality, and the effects or mechanisms of cells on male reproduction. Future trends in this field should concentrate on the relationship between male fertility and energy metabolism, as well as the endocrine function of adipose tissue. This study comprehensively analyzes the current research status and global trends in obesity and male reproductive disorders. We also discuss the future developments in this field, making it easier for researchers to understand its developmental history, current status, and trends, providing valuable reference for effective exploration in this area.

Sex-Dependent Changes in Gonadotropin-Releasing Hormone Neuron Voltage-Gated Potassium Currents in a Mouse Model of Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is the most common focal epilepsy in adults, and people with TLE exhibit higher rates of reproductive endocrine dysfunction. Hypothalamic gonadotropin-releasing hormone (GnRH) neurons regulate reproductive function in mammals by regulating gonadotropin secretion from the anterior pituitary. Previous research demonstrated GnRH neuron hyperexcitability in both sexes in the intrahippocampal kainic acid (IHKA) mouse model of TLE. Fast-inactivating A-type (I A) and delayed rectifier K-type (I K) K+ currents play critical roles in modulating neuronal excitability, including in GnRH neurons. Here, we tested the hypothesis that GnRH neuron hyperexcitability is associated with reduced I A and I K conductances. At 2 months after IHKA or control saline injection, when IHKA mice exhibit chronic epilepsy, we recorded GnRH neuron excitability, I A, and I K using whole-cell patch-clamp electrophysiology. GnRH neurons from both IHKA male and diestrus female GnRH-GFP mice exhibited hyperexcitability compared with controls. In IHKA males, although maximum I A current density was increased, I K recovery from inactivation was significantly slower, consistent with a hyperexcitability phenotype. In IHKA females, however, both I A and I K were unchanged. Sex differences were not observed in I A or I K properties in controls, but IHKA mice exhibited sex effects in I A properties. These results indicate that although the emergent phenotype of increased GnRH neuron excitability is similar in IHKA males and diestrus females, the underlying mechanisms are distinct. This study thus highlights sex-specific changes in voltage-gated K+ currents in GnRH neurons in a mouse model of TLE and suggesting potential sex differences in GnRH neuron ion channel properties.

High Carbohydrate, Fat, and Protein Diets Have a Critical Role in Folliculogenesis and Oocyte Development in Rats.

To date, there is no comparative data on the effects of carbohydrates, fat, and proteins, which are macronutrients, on female reproductive functions. Therefore, in this study, we investigated the effects of diets enriched with carbohydrates, fats, and proteins on folliculogenesis and oocyte development in female rats. 21-day-old rats that were just weaned were divided into 4 groups: control, carbohydrate, fat, and protein. The control group was fed with standard chow and the carbohydrate, fat, and protein groups were fed diets enriched with 75% carbohydrate, 60% fat, and 50% protein for 11 weeks, respectively. It was found that high-fat and high-protein diets caused an increase in the estrous cycle length compared to carbohydrate group (p < 0.05). Graafian follicle number decreased in the protein group compared to the control (p < 0.05). However, the atretic follicle number was higher in the fat group compared to the control group (p < 0.05). In the carbohydrate group, Zp1 was found to be lower than the control and protein groups, Zp2 was found to be lower than the control, and Zp3 was found to be lower than the fat group (p < 0.05). While BMP15 was similar between groups (p > 0.05), GDF9 was lower in all diet groups compared to the control (p < 0.05). Foxo3a was lower in the protein group compared to carbohydrate and control (p < 0.05). GAS2 was found to be higher in the control group than the fat group, and higher in the carbohydrate group than the fat and protein groups (p < 0.05). FSH, LH, Progesterone, and E2 levels were higher in all three diet groups than in the control (p < 0.05). Also, significant differences were observed between the groups regarding adiponectin, resistin, and leptin levels. Taken together, high carbohydrate, fat, and protein intake are associated with impairment of the menstrual cycle, depletion of the developing follicle types, and altered expression of folliculogenesis-specific genes and hormones. Therefore, long-term macronutrient diets may result in shortened reproductive periods and reduced fertilization potential in females in the long run.

The Effect of Dietary Plant-Derived Omega 3 Fatty Acids on the Reproductive Performance and Gastrointestinal Health of Female Rabbits.

This study examined the effects of extruded linseed and algae Padina pavonica extract on the reproductive performance, milk production, and gastrointestinal health of female rabbits. Thirty-six nulliparous New Zealand White female rabbits were randomly assigned to three groups (n = 12) with different diets. The control group (CNT) received a standard diet, while the other two groups received modified isoenergetic diets in which part of the CNT diet ingredients were replaced with 5% extruded linseed (L5%) and 5% extruded linseed plus 0.2% Padina pavonica algae extract (L5%PP). The rabbits were monitored from artificial insemination until the weaning of the rabbit kits, evaluating different reproductive parameters. Our results indicate that extruded linseed and alga Padina pavonica extract did not affect the feed intake or body weight of female rabbits. Additionally, no clinically significant histological changes were observed at the gastrointestinal level. The reproductive parameters, including litter size, litter weight, and milk yield, showed no significant differences among groups. Notably, perinatal and pre-weaning mortalities were reduced in litters born to females receiving omega-3 integrated diets (p < 0.05). While these findings are promising, further studies are needed to confirm these results and explore the specific mechanisms by which omega-3 affects reproductive function and litter health.

Adverse impacts of particulate matter air pollution on female and male reproductive function.

Particulate matter (PM) air pollution consists of liquid and solid particles, which are categorized by size as less than 10 (PM10) μm, 2.5 (PM2.5) μm, or 0.1μm (PM0.1 or ultrafine) in aerodynamic diameter and which vary in composition depending on the sources. PM exposure is ubiquitous and has been associated with many adverse health effects. This narrative review focuses on epidemiological and experimental studies that investigated the effects of PM exposure on female and male reproduction and on pregnancy.μ.

Investigating the Effects of COVID-19 on Sperm in Male Smokers: A Prospective Integrated Proteomic and Metabolomic Study

Notable variations in semen parameters among non-smoking males have been documented post-COVID-19 pandemic. The role of smoking as a significant contributing factor to male infertility has been substantiated. Does the combined effect of smoking and SARS-CoV-2 infection impact male reproductive function? A prospective descriptive cohort study was performed using data from 90 smoking and 90 non-smoking males before and after coronavirus infection in a single center over a period of 3 months. Semen samples were collected before and within 15 days after COVID-19 infection, ensuring no more than three months elapsed between the two collections. The semen parameters evaluated included volume, concentration, progressive motility, normal morphology, and DNA fragmentation rate. Proteomic and metabolomic studies were further used to explore the differences between groups. Both non-smokers and smokers exhibited a marked reduction in sperm concentration, progressive motility, and normal morphology rate. Additionally, an increase in sperm DNA fragmentation index was noted for non-smokers and smokers. In the non-smoking group, dysregulation proteins including SEMG1, SEMG2 and DNAH5, and metabolites including L-glutamine, cis-9-Palmitoleic acid and Linoleamide were observed. In smokers, dysregulation proteins including SMCP, ROPN1B and IZUMO4, alongside metabolites including carnitine, gamma-Glutamylglutamic acid, and hypoxanthine were found. Comparative analysis between smoking and non-smoking patients post-COVID-19 also revealed significant differences in semen concentration, morphology and sperm DNA fragmentation rate. Dysregulated proteins including HSPA5, HSPA2 and PGK2, and metabolites such as acetylcarnitine, oxaloacetate and nicotinate were associated with impaired sperm function. Our study demonstrates that the virus also significantly compromises sperm quality in smoking males, who experience more pronounced declines post-infection compared to their non-smoking counterparts. This research underscores the necessity for comprehensive fertility assessments for smoking males after recovering from COVID-19.

A heterozygous SPRY4 variant identified in female infertility characterized by reduced oocyte potential and early embryonic arrest.

Can novel genetic factors contributing to early embryonic arrest in infertile patients be identified, along with the underlying mechanisms of the pathogenic variant? We identified a heterozygous variant in the SPRY4 (sprouty RTK signaling antagonist 4) in infertile patients and conducted in vitro and in vivo studies to investigate the effects of the variant/deletion, highlighting its critical role in female reproductive health. SPRY4 acts as a negative regulator of receptor tyrosine kinases (RTKs) and functions as a tumor suppressor. Its abnormal expression can lead to recurrent miscarriage by affecting trophoblast function. In mice, Spry4 knockout (KO) leads to craniofacial anomalies and growth defects. A human study links the SPRY4 variant to a male patient with isolated hypogonadotropic hypogonadism (IHH), hypothetically impacting gonadotropin-releasing hormone (GnRH) neurons, and causing reproductive dysfunctions. SPRY4 is thus potentially integral in regulating endocrine homeostasis and reproductive function. To date, no study has reported SPRY4 variants associated with female fertility, and a causal relationship has not been established with functional evidence. Whole-exome sequencing (WES) was performed in 392 infertile women who suffered from primary infertility of unknown reason, and the heterozygous SPRY4 variant were identified in one independent family. The infertile patients presenting were recruited from July 2017 to November 2023. Women diagnosed with primary infertility were recruited from the Reproduction Center of Zhongshan Hospital, Fudan University. Genomic DNA was extracted from peripheral blood for WES analysis. The SPRY4 variant were identified through WES, in silico analysis, and variant screening. All variants were confirmed by Sanger sequencing. The effects of the variants were investigated in human embryonic kidney (HEK) 293T (HEK293T) cells via western blotting, and in mouse oocytes and embryos through complementary RNA (cRNA) injection, RNA sequencing, fluorescence, absorbance, and RT-qPCR assays. Gene function was further examined in Spry4 KO mice via histology, western blotting, ELISA, and RT-qPCR assays. We identified a missense heterozygous pathogenic variant in SPRY4 (GRCh38, GenBank: NM_030964.5, c.157C>T p.(Arg53Trp), rs200531302) that reduces SPRY4 protein levels in HEK293T cells and disrupts the redox system and mitochondrial function in mouse oocyte, and perturbs developmental potential in mouse embryos. These phenotypes could be partially reversed by the exogenous addition of Nrf1 cRNA. Additionally, Spry4-/- mice exhibit ovarian oxidative stress and decreased ovarian function. Due to the limited WES data and population, we identified only one family with a SPRY4 mutation. The deeper mechanism and therapeutic strategy should be further investigated through mutant mice and recovery experiment. Our study has identified a pathogenic variant in SPRY4 associated with early embryonic arrest in humans. These findings enhance our understanding of the role of SPRY4 in early embryonic development and present a new genetic marker for female infertility. This work was supported by the National Natural Science Foundation of China (82071643 and 82171655) and Natural Science Foundation of Shanghai (22ZR1456200). None of the authors have any competing interests. N/A.

Morphology of endometrial inflammatory changes in foci of endometriosis and adenomyosis

The high prevalence of endometriosis, its impact on menstrual and reproductive functions, obstetric complications, and the quality of life of women in the reproductive age determines the urgency of the problem.The objective: to assess the prevalence of inflammatory changes in foci of heterotopic endometrium in patients with endometriosis and adenomyosis.Materials and methods. 92 women of reproductive age – from 21 to 46 years old – who applied for surgical treatment for symptomatic adenomyosis (47 women – 1st group) and ovarian endometriosis (45 patients – 2nd group), and 30 practically healthy women of the same age (control group) were examined.Histological examination of adenomyosis and ovarian endometriosis biopsies was performed using a light microscope at magnifications of 40 and 100. For immunohistochemical examination, primary and secondary antibodies were used to determine CD34, CD68, and CD138 markers.Results. In patients with adenomyosis and ovarian endometriosis the following concomitant gynecological pathologies as uterine fibroids, endometrial hyperplasia, chronic endometritis, chronic abnormal uterine bleeding, the frequency of which is significantly higher in adenomyosis, were diagnosed. This may indicate the pathogenetic role of chronic inflammation in the development of these pathological conditions.In patients with adenomyosis the positive expression of CD68 in the epithelial component of heterotopias was determined in 8 (17.0±5.6%) women, and in 4 (8.9±4.2%) women with ovarian endometriosis, which indicated a low phagocytic activity. During the assessment of CD34 expression in vessel walls and the stromal component of endometrioid heterotopias, a positive reaction was determined in 16 (34.0±6.9%) patients with adenomyosis and in 10 (22.2±6.2%) patients with ovarian endometriosis, which reflects the processes of neoangiogenesis and the activity of the pathological process.Positive expression of CD138 in endometrioid heterotopias prevailed in the group of patients with adenomyosis – 12 (25.5±6.4%) cases versus 4 (8.9±4.2%) cases in the group of patients with ovarian endometriosis (p&lt;0.05). This confirmed the histological results and clinical data regarding the presence of chronic endometritis and isthmocele.Conclusions. The identified inflammatory changes, weak phagocytic activity and signs of neoangiogenesis in foci of heterotopic endometrium are more significant in patients with adenomyosis, which is confirmed by clinical and morphological data.

Hormonal status of patients with infertility and post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a mental disorder that occurs after a psychologically or physically traumatic event, and characterized by three main clusters of posttraumatic symptoms, as well as chronic and significant disturbances in emotion regulation, identity, and relationships. PTSD is more common in women, which suggests a role for the regulation of female sex hormones in its development.The objective: to study the hormonal status of women with infertility and PTSD.Materials and methods. 112 women with infertility were examined, who were divided into groups depending on the PTSD criteria. The I group included 36 women with PTSD criteria, who were diagnosed with infertility before the onset of the traumatic factor, the II group – 31 patients with fertility disorders which were diagnosed on the background of PTSD, the III group – 45 women with infertility and without signs of PTSD, the control group consisted of 50 healthy women who applied for a routine preventive examination.In all patients, on the 3rd–5th day of the menstrual cycle, the concentrations of prolactin, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone were determined in the blood serum, in the saliva – cortisol, on the 21st day of the cycle – in the blood serum progesterone.Results. It was established that in women with infertility that was developed after the traumatic factor, the prolactin content is significantly higher (59.5±18.9 ng/ml) than in other groups of patients with fertility disorders (36.9±12.3 ng/ml in I group, 34.3±17.9 ng/ml – in the III group) and in the group of healthy women (13.5±5.6 ng/ml). The concentration of estradiol in the I group was within the reference values for the follicular phase of the cycle, but significantly lower (23.4±3.6 pg/ml) than in women of the other groups (from 87.6±14.6 pg/ml in the III group to 103.5±27.8 pg/ml in the group of healthy women). The average concentration of progesterone in the I (3.4±2.7 pg/ml) and II (4.1±2.9 pg/ml) groups was within the reference values, but was probably lower than that of healthy women (23.6±4.9 pg/ml), as well as women with infertility without signs of PTSD (19.4±5.1 pg/ml).In this study the patients with infertility which has developed on the background of PTSD had LH values within the reference normal range (2.0±0.5 U/L), but several times lower than in women with other reasons of infertility (12.0±3.6 U/l – in women with infertility before the development of PTSD, 6.0±1.9 U/l – in women with infertility without PTSD criteria) and in healthy women (9.2±3.4 U/l).An increased level of testosterone beyond the reference values was found only in women of the II group (3.3±1.9 nmol/l), in the other groups the average testosterone concentration ranged from 1.3±0.6 nmol/l in healthy women to 1.5±0.9 nmol/l in the I group and 1.8±0.7 nmol/l in women with infertility without signs of PTSD. Patients with PTSD are characterized by an increased level of cortisol in saliva, which indicates a prolonged reaction of the body to the trauma (8.8±0.3 ng/ml – in the I group, 10.3±0.4 ng/ml – in the II group), in groups without PTSD the level of this hormone in saliva was almost twice as low (5.4±0.2 ng/ml – in the III group and 5.9±0.3 ng/ml – in healthy women).Conclusions. 1. The patients with PTSD and infertility are characterized by high concentrations of cortisol in saliva and a decreased progesterone level in blood serum.2. In patients who had fertility disorders before a stressful event, a decreased estrogen concentration and an increased luteinizing hormone level were found in blood serum, which indicates endocrine disorders as a cause of infertility.3. Prolactin and testosterone levels were found to be higher in the patients with infertility that was developed after a traumatic event than in other women with reproductive function disorders. Both factors are pathogenetically related to the pathological reaction to stress.

Sexual and reproductive health: level of knowledge and source of information in adolescence.

To date, there is a lack of a structured national plan of sexual education in Italy, with large interregional differences and poor uniformity in the promotion and learning of sexual health. The aim of this study was to evaluate the level of knowledge on sexuality and reproductive function among adolescents before and after a sexual education program, considering gender differences in the results. A longitudinal and interventional study was conducted on high school students. Six sessions for each class were carried out by a multidisciplinary team. Anonymous questionnaires were administered to investigate basic knowledge of human sexuality and reproduction before and after intervention. Participants were high school students who completed the questionnaires. Outcomes included pre and posttest answers on the knowledge questionnaire in study population. We obtained data from 842 high school students (mean ± SD age, 16.11 ± 1.74years). The main informative sources on sexuality were social media in 37.9% of participants; family, school, and scientific material were the main source in 15.1%, 5.2%, and 4.4%, respectively. A total score of 12.6 ± 3.4 (range, 1-20) was obtained on the knowledge questionnaire; specifically, the score was higher in females than males (12.8 ± 3.4 vs 11.9 ± 3.4, P = .0001). In males and females, a statistically significant increase in level of knowledge was found after the multidisciplinary intervention (14.5 ± 3.6, P = .0001). The lack of sexual education programs in schools in Italy compels adolescents to refer to frequently unreliable sources, such as social media and peers, contributing to misinformation and adoption of risky sexual behaviors. This study is based on a large sample size and highlights the importance of sexual education programs. The main limitations are a greater representation of the female population and the inclusive nature of the school (ie, an artistic school), attracting students who identify with sexual minorities. Adolescents have limited knowledge about sexuality and reproduction, with a notable gender disparity; sexual education programs in schools, providing information from sexuality experts, led to a substantial increase in knowledge and a reduction in the gender gap.

A newly-constructed technology to remove and recover diethyl phthalate from wastewater by using the instant plasticization assembly ability of PVC

Diethyl phthalate (DEP) is a typical environmentally organic pollutant, widely used in the production process of polyvinyl chloride (PVC) to improve the flexibility of plastic materials. Its interaction with living organisms can inflict considerable harm to reproductive system functions. This research aims to utilize tetrahydrofuran (THF) to selectively break the chemical bonds in PVC molecules to provide more adsorption sites. Then incorporates the plasticizing assembly process of PVC to instantly remove and recover DEP from wastewater, achieving waste utilization, and sustainable environmental development. The research found that PTFR with a concentration of around 75 mg/L shows the best DEP removal efficiency. Sequencing batch processing removes more DEP compared to direct processing under the same material usage conditions. Furthermore, the recovery rate of DEP can reach over 90%. The technology demonstrates notable enhancements in removal efficiency and adsorption duration when compared to conventional adsorption techniques. This research has established an instant and efficient method for DEP removal, providing a new idea and technology for plasticizer treatment in practical wastewater.

Protective effect of afamin protein against oxidative stress related injury in human ovarian granulosa cells.

Ovarian granulosa cells (GCs) play crucial roles in follicular growth and development. Their normal function is influenced by various factors, including oxidative stress, which is a significant factor. Afamin protein is a vitamin E-specific binding protein that acts as a vitamin E carrier in follicular fluid. Although the mechanism of the protective effect of afamin on human ovarian GCs is still unclear, there is evidence it has an antioxidant effect in neuronal cells. In this study, we investigated the protective effects of afamin proteins on testosterone propionate (TP)-induced ovarian GCs using a human ovarian tumor granulosa cell line (KGN). The results showed that afamin reduced TP-induced oxidative stress in KGN cells by decreasing the levels of oxidative damage markers, enhancing the activity of antioxidant enzymes, and exerting a protective effect on GCs. Supplementation with afamin repaired mitochondrial dysfunction by improving mitochondrial membrane potential damage and ATP levels. It counteracted TP-induced apoptosis by decreasing the activity of Caspase-3 and upregulating the expression of the anti-apoptotic gene (BCL-2) while downregulating the expression of the pro-apoptotic gene BCL-2-associated X protein (BAX). In addition, afamin regulated the expression of genes related to ovarian steroid hormone synthesis, ameliorating the endocrine dysfunction observed in TP-induced KGN cells. Therefore, Afamin proteins may serve as important complementary factors that protect GCs from other types of damage, such as oxidative stress, and may help improve ovarian follicle quality and female reproductive function.

Testicular fibrosis pathology, diagnosis, pathogenesis, and treatment: A perspective on related diseases.

Testicular fibrosis is a chronic and progressive condition characterized by the excessive deposition of extracellular matrix proteins. This process leads to fibrotic remodeling, damage to testicular tissue, and the irreversible loss of male reproductive function. However, there is currently a lack of comprehensive reviews systematically elucidating the pathology, diagnosis, pathogenesis, and treatment of testicular fibrosis from the perspectives of different related diseases. This review addresses these aspects of testicular fibrosis, with a particular emphasis on elucidating the underlying mechanisms of testicular cells. It provides insights that can be relevant for future research and clinical interventions.

Expression of the apelin system in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of apelin on LH and FSH secretion

Reproductive success requires considerable energy investment. Research has shown that some adipokines, i.e. the hormones produced in adipose tissue, affect reproductive functions by influencing all structures of the hypothalamic-pituitary-ovarian axis. Apelin is a recently identified member of the adipokine family. To the best of the authors' knowledge, this is the first study to investigate the gene and protein expression of the apelin system (the apelin hormone and the apelin receptor, APJ) in the anterior (AP) and posterior (PP) pituitary lobes of the domestic pig during different phases of the oestrous cycle (days 2 to 3, 10 to 12, 14 to 16, and 17 to 19) and in early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28). It was also assumed that apelin participates in the regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and influences Akt, MAPK/Erk1/2, and AMPK signalling pathways in the AP during the oestrous cycle. Apelin, APJ mRNAs and proteins were detected in both pituitary lobes. Apelin was identified in gonadotropes, somatotropes, lactotropes, and thyrotropes. The study also revealed that apelin and APJ mRNA/protein levels fluctuate during the oestrous cycle and early gestation. Apelin affects basal, GnRH- and/or insulin-stimulated gonadotropin secretion in some phases of the cycle, as well as the phosphorylation of Akt, MAPK/Erk1/2, and AMPK proteins in AP cells. These findings suggest that apelin may be produced locally in the pituitary and that this gland is receptive to apelin's action. The study also suggest that apelin may influence female reproductive functions by controlling the release of LH and FSH from AP cells, and that it affects Akt, MAPK/Erk1/2, and AMPK signalling pathways.

A million-cow genome-wide association study of productive life in U.S. Holstein cows

BackgroundProductive life (PL) of a cow is the time the cow remains in the milking herd from first calving to exit from the herd due to culling or death and is an important economic trait in U.S. Holstein cattle. The large samples of Holstein genomic evaluation data that have become available recently provided unprecedented statistical power to identify genetic factors affecting PL in Holstein cows using the approach of genome-wide association study (GWAS).MethodsThe GWAS analysis used 1,103,641 Holstein cows with phenotypic observations on PL and genotypes of 75,282 single nucleotide polymorphism (SNP) markers. The statistical tests and estimation of SNP additive and dominance effects used the approximate generalized least squares method implemented by the EPISNPmpi computer program.ResultsThe GWAS detected 5390 significant additive effects of PL distributed over all 29 autosomes and the X–Y nonrecombining region of the X chromosome (Chr31). Two chromosome regions had the most significant and largest cluster of additive effects, the SLC4A4-GC-NPFFR2 (SGN) region of Chr06 with pleiotropic effects for PL, fertility, somatic cell score and milk yield; and the 32–52 Mb region of Chr10 with peak effects for PL in or near RASGRP1 with many important immunity functions. The dominance tests detected 38 significant dominance effects including 12 dominance effects with sharply negative homozygous recessive genotypes on Chr18, Chr05, Chr23 and Chr24.ConclusionsThe GWAS results showed that highly significant genetic effects for PL were in chromosome regions known to have highly significant effects for fertility and health and a chromosome region with multiple genes with reproductive and immunity functions. SNPs with rare but sharply negative homozygous recessive genotypes for PL existed and should be used for eliminating heifers carrying those homozygous recessive genotypes.

Влияние COVID-19 на спермиологические показатели у мужчин репродуктивного возраста

Introduction: The new coronavirus infection is dangerous not only in the acute period of the disease, but also during the period of convalescence, causing various complications. The long-term effects of the SARS-CoV 2 virus on male reproductive function are an important prognostic factor requiring comprehensive study. Purpose of the study: to study the long-term results of the impact of COVID-19 mild to moderate severity on spermological indicators in men of reproductive age. Materials and Methods: the study included 14 healthy men of reproductive age who were not vaccinated against COVID 19, who had negative results of an STI examination, normal spermological parameters, TUNEL test values &lt;15%, who subsequently suffered a viral infection caused by the SARS-CoV 2 virus of mild and moderate severity, with persistent negative results of an STI examination. Results: а comparative analysis of the results of spermograms of patients before and after COVID 19 showed that the total number of spermatozoa before and after the disease (422.5 ± 53.9 and 410.2 ± 176.9 million, respectively), the indicator of the number of spermatozoa with progressive translational (PR) mobility (56.4 ± 8.7 and 54.4 ± 8.0%, respectively), morphologically normal male gametes before and after 3 months after COVID-19 (21.2 ± 4.3 and 20.2 ± 3.6%, respectively) are comparable. Normozoospermia was observed in all cases, TUNEL test values &lt;15%. Conclusion: in the conducted study, mild and moderate COVID-19 did not have a clinically significant effect on the spermological parameters of men 3 months after COVID-19. Keywords: COVID-19, SARS-CoV 2 virus, spermological indicators, TUNEL-test.

Regulatory Involvement of Kisspeptin in Energy Balance and Reproduction.

The hypothalamic-pituitary-gonadal axis, which regulates steroidogenesis and germ cell formation, closely regulates the reproduction process. Nonetheless, other chemical mediators, such as kisspeptin, influence this axis. Kisspeptin is a hypothalamic neuropeptide that modulates the function of this axis and also plays a central role in energy balance. The present study reviews the impact and associated mechanisms of kisspeptin on male and female reproduction based on available evidence in the literature. Kisspeptin and its neurons exert anorexigenic activity, thus maintaining adequate energy balance for optimal reproductive function. Also, they stimulate the release of GnRH, resulting in the optimal performance of gonadal physiological processes viz. production of steroid sex hormones and germ cells. However, studies linking kisspeptin to reproduction are yet scanty. Hence, studies exploring the upstream and downstream signaling pathways activated by kisspeptin concerning reproduction in an attempt to better understand the associated mechanisms of the regulatory activities of kisspeptin on reproduction are recommended. In addition, potential factors that may modulate kisspeptin activities may be useful in the management of infertility and perhaps, in the development of contraceptives for those who do not intend to achieve conception.

Reproductive development in Trithuria submersa (Hydatellaceae: Nymphaeales): the involvement of AGAMOUS-like genes

Main conclusionIn the early diverging angiosperm Trithuria submersaTsAG1 and TsAG2 are expressed in different flower organs, including bracts, while TsAG3 is more ovule-specific, probably functioning as a D-type gene.Species of Trithuria, the only genus of the family Hydatellaceae, represent ideal candidates to explore the biology and flower evolution of early diverging angiosperms. The life cycle of T. submersa is generally known, and the “reproductive units” are morphologically well described, but the availability of genetic and developmental data of T. submersa is still scarce. To fill this gap, a transcriptome analysis of the reproductive structures was performed and presented in this work. This analysis provided sequences of MADS-box transcription factors, a gene family known to be involved in flower and fruit development. In situ hybridization experiments on floral buds were performed to describe the spatiotemporal expression patterns of the AGAMOUS genes, revealing the existence of three AG genes with different expression domains in flower organs and in developing ovules. Trithuria may offer important clues to the evolution of reproductive function among early angiosperms and Nymphaeales in particular, and this study aims to broaden relevant knowledge regarding key genes of reproductive development in non-model angiosperms, shaping first flower appearance and evolution.