Impaired Fertility Research Articles

The Role of N6-methyladenosine Modification in Gametogenesis and Embryogenesis: Impact on Fertility.

The most common epigenetic modification of messenger RNAs (mRNAs) is N6-methyladenosine (m6A), which is mainly located near the 3' untranslated region of mRNAs, near the stop codons, and within internal exons. The biological effect of m6A is dynamically modulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). By controlling post-transcriptional gene expression, m6A has a significant impact on numerous biological functions, including RNA transcription, translation, splicing, transport, and degradation. Hence, m6A influences various physiological and pathological processes, such as spermatogenesis, oogenesis, embryogenesis, placental function, and human reproductive system diseases. During gametogenesis and embryogenesis, genetic material undergoes significant changes, including epigenomic modifications such as m6A. From spermatogenesis and oogenesis to the formation of an oosperm and early embryogenesis, m6A changes occur at every step. m6A abnormalities can lead to gamete abnormalities, developmental delays, impaired fertilization, and maternal-to-zygotic transition blockage. Both mice and humans with abnormal m6A modifications exhibit impaired fertility. In this review, we discuss the dynamic biological effects of m6A and its regulators on gamete and embryonic development and review the possible mechanisms of infertility caused by m6A changes. We also discuss the drugs currently used to manipulate m6A and provide prospects for the prevention and treatment of infertility at the epigenetic level.

Simulated climate change and atrazine contamination can synergistically impair zebrafish testicular function

Elements that interfere with reproductive processes can have profound impacts on population and the equilibrium of ecosystems. Global warming represents the major environmental challenge of the 21st century, as it will affect all forms of life in the coming decades. Another coexisting concern is the persistent pollution by pesticides, particularly the herbicide Atrazine (ATZ), which is responsible for a significant number of contamination incidents in surface waters worldwide. While it is hypothesized that climate changes will significantly enhance the toxic effects of pesticides, the actual impact of these phenomena remain largely unexplored. Here, we conducted a climate-controlled room experiment to assess the interactive effects of the projected 2100 climate scenario and environmentally realistic ATZ exposures on the reproductive function of male zebrafish. The gonadosomatic index significantly decreased in fish kept in the extreme scenario. Cellular alterations across spermatogenesis phases led to synergic decreased sperm production and increased germ cell sloughing and death. ATZ exposure alone or combined with climate change effects, disrupted the transcription levels of key genes involved in steroidogenesis, hormone signaling and spermatogenesis regulation. An additive modulation with decreased 11-KT production and increased E2 levels was also evidenced, intensifying the effects of androgen/estrogen imbalance. Moreover, climate change and ATZ independently induced oxidative stress, upregulation of proapoptotic gene and DNA damage in post-meiotic germ cell, but the negative effects of ATZ were greater at extreme scenario. Ultimately, exposure to simulated climate changes severely impaired fertilization capacity, due to a drastic reduction in sperm motility and/or viability. These findings indicate that the future climate conditions have the potential to considerably enhance the toxicity of ATZ at low concentrations, leading to significant deleterious consequences for fish reproductive function and fertility. These may provide relevant information to supporting healthcare and environmental managers in decision-making related to climate changes and herbicide regulation.

MCM8 interacts with DDX5 to promote R-loop resolution

MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.

Survivorship after adolescent and young adult cancer: models of care, disparities, and opportunities.

Survivors of adolescent and young adult (AYA; age 15-39 years at diagnosis) cancer are a growing population with the potential to live for many decades after treatment completion. Survivors of AYA cancer are at risk for adverse long-term outcomes including chronic conditions, secondary cancers, impaired fertility, poor psychosocial health and health behaviors, and financial toxicity. Furthermore, survivors of AYA cancer from racially minoritized and low socioeconomic status populations experience disparities in these outcomes, including lower long-term survival. Despite these known risks, most survivors of AYA cancer do not receive routine survivorship follow-up care, and research on delivering high-quality, evidence-based survivorship care to these patients is lacking. The need for survivorship care was initially advanced in 2006 by the Institute of Medicine. In 2019, the Quality of Cancer Survivorship Care Framework (QCSCF) was developed to provide an evidence-based framework to define key components of optimal survivorship care. In this commentary focused on survivors of AYA cancer, we apply the QCSCF framework to describe models of care that can be adapted for their unique needs, multilevel factors limiting equitable access to care, and opportunities to address these factors to improve short- and long-term outcomes in this vulnerable population.

Oral exposure to polystyrene nanoplastics altered the hypothalamic-pituitary-testicular axis role in hormonal regulation, inducing reproductive toxicity in albino rats.

Nanoplastics can be considered a novel contaminant for the environment because of their extensive applications in modern society, which represents a possible threat to humans. Nevertheless, the negative effect of polystyrene nanoplastics (PS-NPs) on male reproduction, fertility, and progeny outcomes is not well known. Thus, the aim of the present work was to calculate the median lethal dose (LD50) and investigate the consequences of exposure to PS-NPs (25 nm) on male reproductive toxicity. This investigation first determined the LD50 of PS-NPs in male Wistar rats, and then in a formal study, 24 rats were distributed into three groups (n = 8): the control group; the low-dose group (3 mg/kg bw); and the high-dose group (10 mg/kg bw) of PS-NPs administered orally for 60 days. On the 50thday of administration, the fertility test was conducted. The LD50 was determined to be 2500 mg/kg. PS-NP administration induced significant alternations, mainly indicating mortality in the high-dose group, a significant elevation in body weight gain, declined sperm quality parameters, altered reproductive hormonal levels, thyroid endocrine disruption, an alternation of the normal histo-architecture and the histo-morphometric analysis of the testes, and impaired male fertility. Altogether, the current findings provide novel perspectives on PS-NP general toxicity with specific reference to male reproductive toxicity.

Insights into disability and psycho-social care of patients with inflammatory bowel disease.

In recent years, the concept of disability has increasingly garnered attention as a crucial long-term target of inflammatory bowel disease (IBD) management. The treatment paradigm has changed dramatically from full control of the disease (clinical and endoscopic remission) toward physical and emotional well-being with the goal of preventing disability and normalizing quality of life. However, in certain cases, despite achieving good disease control, patients may still experience symptoms associated with disability, and reduced emotional wellness. These symptoms can significantly impact various biopsychosocial factors, including interpersonal relationships, educational or work-related activities, body image, and sexual functioning. Nevertheless, they often remain overlooked in the context of IBD care. In this narrative review, we aim to shed light on the burden of certain disability-related symptoms such as bowel urgency, sexual dysfunction, impaired fertility and fatigue, emphasizing the importance of acknowledging and validating them in a clinical setting. There is a demanding need for comprehensive care for IBD patients, with IBD clinicians being mindful of the psychosocial challenges faced by their patients. Providing timely and appropriate management of these challenges alongside IBD treatment is key to achieving holistic remission and enhancing the overall quality of life while reducing disability.

Primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is arare genetic disorder with avariable clinical phenotype that is accompanied by reduced motility of the cilia in the respiratory tract and numerous other organs. This leads to various characteristic symptoms and disease manifestations, primarily affecting the lungs (chronic persistent productive cough, bronchiectasis), the nose and paranasal sinuses (chronic persistent rhinitis or rhinosinusitis) as well as the middle ear (chronic otitis media, middle ear effusion). Moreover, PCD is associated with impaired fertility or lateralization defects (situs anomalies, congenital heart defects). The diagnostics of PCD are complex and require acombination of several sophisticated instrument-based diagnostic procedures. Through thorough history taking and evaluation, suspected cases can be comparatively well identified based on typical clinical features and referred to further diagnostics. In recent years, molecular genetic analysis through panel diagnostics or whole exome and whole genome sequencing, has gained in importance as this enables affected individuals to participate in disease-specific and genotype-specific clinical trials. Although the current treatment is purely symptomatic, the earliest possible diagnosis is crucial for connecting patients to specialized PCD centers, which can have asignificant impact on the clinical course of the affected individuals.

METTL3-dependent m6A modification facilitates decreased endometrial decidualization via attenuation of MET in endometriosis.

Failure to induce mesenchymal-epithelial transition (MET) during stromal cell decidualization can lead to consequences such as impaired fertility in patients with endometriosis. METTL3-mediated m6A modification plays an important role in attenuating MET and defective decidualization of endometrial stromal cells and contributes to the development of reduced endometrial receptivity in endometriosis. Mesenchymal-epithelial transition (MET)-mediated endometrial decidualization is pivotal for achieving endometrial receptivity and successful pregnancy. We observed blockade of MET in the eutopic secretory endometrium of patients with endometriosis, but the underlying mechanism is unknown. In this study, real-time PCR was used to detect PRL and IGFBP1 expression, whereas western blotting was used to detect the expression of MET markers and METTL3. Phalloidin staining was used to identify changes in cell morphology. M6A levels were quantified using a colorimetric method and m6A dot blots, and functional analysis was performed using spheroid adhesion assays. We first found that increased E-cadherin expression was accompanied by decreased vimentin and Slug expression in the eutopic secretory endometrium of individuals with endometriosis. We also detected a significant increase in both the m6A level and the expression of the related methyltransferase METTL3. Finally, METTL3 expression was negatively correlated with PRL, IGFBP1, and MET markers expression. Collectively, our findings suggest that METTL3 mediates m6A modification, thereby inhibiting MET formation within the eutopic secretory endometrium of patients with endometriosis. Increased METTL3-mediated m6A modification plays a crucial role in attenuating MET formation and decidualization impairment in endometrial stromal cells, ultimately contributing to compromised endometrial receptivity in individuals with endometriosis. These insights could lead to the identification of potential therapeutic targets for improving both endometrial receptivity and pregnancy rate among individuals affected by endometriosis.

Toxicological inhalation studies in rats to substantiate grouping of zinc oxide nanoforms

BackgroundSignificant variations exist in the forms of ZnO, making it impossible to test all forms in in vivo inhalation studies. Hence, grouping and read-across is a common approach under REACH to evaluate the toxicological profile of familiar substances. The objective of this paper is to investigate the potential role of dissolution, size, or coating in grouping ZnO (nano)forms for the purpose of hazard assessment. We performed a 90-day inhalation study (OECD test guideline no. (TG) 413) in rats combined with a reproduction/developmental (neuro)toxicity screening test (TG 421/424/426) with coated and uncoated ZnO nanoforms in comparison with microscale ZnO particles and soluble zinc sulfate. In addition, genotoxicity in the nasal cavity, lungs, liver, and bone marrow was examined via comet assay (TG 489) after 14-day inhalation exposure.ResultsZnO nanoparticles caused local toxicity in the respiratory tract. Systemic effects that were not related to the local irritation were not observed. There was no indication of impaired fertility, developmental toxicity, or developmental neurotoxicity. No indication for genotoxicity of any of the test substances was observed. Local effects were similar across the different ZnO test substances and were reversible after the end of the exposure.ConclusionWith exception of local toxicity, this study could not confirm the occasional findings in some of the previous studies regarding the above-mentioned toxicological endpoints. The two representative ZnO nanoforms and the microscale particles showed similar local effects. The ZnO nanoforms most likely exhibit their effects by zinc ions as no particles could be detected after the end of the exposure, and exposure to rapidly soluble zinc sulfate had similar effects. Obviously, material differences between the ZnO particles do not substantially alter their toxicokinetics and toxicodynamics. The grouping of ZnO nanoforms into a set of similar nanoforms is justified by these observations.

Preconception depression reduces fertility: a couple-based prospective preconception cohort.

Is preconception depression associated with time to pregnancy (TTP) and infertility? Couples with preconception depression needed a longer time to become pregnant and exhibited an increased risk of infertility. Preconception depression in women contributes to impaired fertility in clinical populations. However, evidence from the general population-especially based on couples-is relatively scant. A couple-based prospective preconception cohort study was performed in 16 premarital examination centers between April 2019 and June 2021. The final analysis included 16521 couples who tried to conceive for ≤6 months at enrollment. Patients with infertility were defined as those with a TTP ≥12 months and those who conceived through ART. Couples' depression was assessed using the Patient Health Questionnaire-9 at baseline. Reproductive outcomes were obtained via telephone at 6 and 12 months after enrollment. Fertility odds ratios (FORs) and infertility risk ratios (RRs) in different preconception depression groups were analyzed using the Cox proportional-hazard models and logistic regression, respectively. Of the 16 521 couples analyzed, 10834 (65.6%) and 746 (4.5%) couples achieved pregnancy within the first 6 months and between the 6th and 12th months, respectively. The median (P25, P75) TTP was 3.0 (2.0, 6.0) months. The infertility rate was 13.01%. After adjusting for potential confounders, in the individual-specific analyses, we found that preconception depression in women was significantly related to reduced odds of fertility (FOR = 0.947, 95% CI: 0.908-0.988), and preconception depression in either men or women was associated with an increased risk of infertility (women: RR = 1.212, 95% CI: 1.076-1.366; men: RR = 1.214, 95% CI: 1.068-1.381); in the couple-based analyses, we found that-compared to couples where neither partner had depression-the couples where both partners had depression exhibited reduced fertility (adjusted FOR = 0.904, 95% CI: 0.838-0.975). The risk of infertility in the group where only the woman had depression and both partners had depression increased by 17.8% (RR = 1.178, 95% CI: 1.026-1.353) and 46.9% (RR = 1.469, 95% CI: 1.203-1.793), respectively. Reporting and recall bias were unavoidable in this large epidemiological study. Some residual confounding factors-such as the use of anti-depressants and other medications, sexual habits, and prior depressive and anxiety symptoms-remain unaddressed. We used a cut-off score of 5 to define depression, which is lower than prior studies. Finally, we assessed depression only at baseline, therefore we could not detect effects of temporal changes in depression on fertility. This couple-based study indicated that preconception depression in individuals and couples negatively impacts couples' fertility. Early detection and intervention of depression to improve fertility should focus on both sexes. This work was supported by grants from the National Natural Science Foundation of China (No. 82273638) and the National Key Research and Development Program of China (No. 2018YFC1004201). All authors declare no conflicts of interest. N/A.

Phoenixin knockout mice show no impairment in fertility or differences in metabolic response to a high-fat diet, but exhibit behavioral differences in an open field test.

Phoenixin (PNX) is a conserved secreted peptide that was identified 10 years ago with numerous studies published on its pleiotropic functions. PNX is associated with estrous cycle length, protection from a high-fat diet, and reduction of anxiety behavior. However, no study had yet evaluated the impact of deleting PNX in the whole animal. We sought to evaluate a mouse model lacking the PNX parent gene, small integral membrane protein 20 (Smim20), and the resulting effect on reproduction, energy homeostasis, and anxiety. We found that the Smim20 knockout mice had normal fertility and estrous cycle lengths. Consistent with normal fertility, the hypothalamii of the knockout mice showed no changes in the levels of reproduction-related genes, but the male mice had some changes in energy homeostasis-related genes, such as melanocortin receptor 4 (Mc4r). When placed on a high-fat diet, the wildtype and knockout mice responded similarly, but the male heterozygous mice gained slightly less weight. When placed in an open field test box, the female knockout mice traveled less distance in the outer zone, indicating alterations in anxiety or locomotor behavior. In summary, the homozygous knockout of PNX did not alter fertility and modestly alters a few neuroendocrine genes in response to a high-fat diet, especially in the female mice. However, it altered the behavior of mice in an open field test. PNX therefore may not be crucial for reproductive function or weight, however, we cannot rule out possible compensatory mechanisms in the knockout model. Understanding the role of PNX in physiology may ultimately lead to an enhanced understanding of neuroendocrine mechanisms involving this enigmatic peptide.

Fertility Preservation in BRCA1/2 Germline Mutation Carriers: An Overview.

BRCA1 and BRCA2 mutations are responsible for a higher incidence of breast and ovarian cancer (from 55% up to 70% vs. 12% in the general population). If their functions have been widely investigated in the onset of these malignancies, still little is known about their role in fertility impairment. Cancer patients treated with antineoplastic drugs can be susceptible to their gonadotoxicity and, in women, some of them can induce apoptotic program in premature ovarian follicles, progressive depletion of ovarian reserve and, consequently, cancer treatment-related infertility (CTRI). BRCA variants seem to be associated with early infertility, thus accelerating treatment impairment of ovaries and making women face the concrete possibility of an early pregnancy. In this regard, fertility preservation (FP) procedures should be discussed in oncofertility counseling-from the first line of prevention with risk-reducing salpingo-oophorectomy (RRSO) to the new experimental ovarian stem cells (OSCs) model as a new way to obtain in vitro-differentiated oocytes, several techniques may represent a valid option to BRCA-mutated patients. In this review, we revisit knowledge about BRCA involvement in lower fertility, pregnancy feasibility, and the fertility preservation (FP) options available.

Star1 gene mutation reveals the essentiality of 11-ketotestosterone and glucocorticoids for male fertility in Nile Tilapia (Oreochromis niloticus)

Steroidogenic acute regulatory protein (Star) plays an essential role in the biosynthesis of corticosteroids and sex steroids by mediating the transport of cholesterol from the outer to the inner membrane of mitochondria. Two duplicated Star genes, namely star1 and star2, have been identified in non-mammalian vertebrates. To investigate the roles of star genes in fish steriodogenesis, we generated two mutation lines of star1−/− and star1−/−/star2−/− in Nile tilapia (Oreochromis niloticus). Previous studies revealed that deficiency of star2 gene caused delayed spermatogenesis, sperm apoptosis and sterility in male tilapia. Our present data revealed that mutation of star genes impaired male fertility. Disordered seminiferous lobules and spermatic duct obstruction were found in the testis of both types of mutants. Moreover, significant decline in semen volume, sperm abnormality and impaired fertility were also detected in star1−/− and star1−/−/star2−/− males. In star1−/− male fish, lipid accumulation, up-regulation of steroidogenic enzymes, and significant decline of androgens were found. Additionally, hyperplasic interrenal cells, elevated steroidogenic gene expression level and decline of serum glucocorticoids were detected in star1 mutants. Intriguingly, either 11-KT or cortisol supplementation successfully rescued the impaired fertility of the star1−/− mutants. Taken together, these results further indicate that Star1 might play critical roles in the production of both 11-KT and glucocorticoids, which are indispensable for the maintenance of male fertility in fish.

Heat‐stress‐induced fertility loss in summer maize (Zea mays L.): Quantitative analysis of contributions from developmental and physiological damage to pollen

AbstractIn recent years, the frequency and intensity of exposure to heat stress have increased gradually, seriously hampering the production of maize. This paper presents a study designed to analyze how the development, physiology and dispersal of pollen from the heat‐resistant maize variety Zhengdan958 and the heat‐sensitive maize variety Xianyu335 are affected by exposure to heat stress during the tasselling stage. Our results showed That exposure to heat stress significantly increased the antioxidant enzyme activity in pollen. Upon visual inspection of the pollen, we found that the lower water content had given rise to wrinkles in the pollen surface, sunken germination pores, and morphological deformations. In addition, the anther dehiscence process was hindered, resulting in a reduced amount of pollen being dispersed. We also found elevated levels of abscisic acid (ABA), jasmonic acid (JA) and its derivatives, indole acetic acid (IAA) and gibberellin‐3 (GA3) in heat‐pollens, as well as elevated ratios of IAA to ABA and ABA to GA3. Ultimately impaired pollen fertility. Summarizing, our experiment revealed that reduced pollen quantity and quality are significant contributors to fertility losses in summer maize exposed to heat stress at anthesis, and we hope that our analysis of the physiological mechanisms involved can contribute to the development of crop management measures aimed at countering the increasingly detrimental effects of heat stress on the production of summer maize.

Bridging the knowledge gap! Health outcomes in informal e-waste workers.

Although several studies analyzed the impact of e-waste recycling on human health, most publications did not differ between e-waste workers and bystanders, such as residents. This could lead to an underestimation of health effects in workers. In addition, frequently reported surrogate findings do not properly reflect clinical significant health outcomes. The aim of this review was to analyze the direct health effects of informal e-waste recycling in informal e-waste workers. According to PRISMA guidelines, we systematically searched 3 databases (Embase®, PubMed®, Web of Science) for studies from low- and middle-income countries published in German or English between 1980 and 1 November 2021. Of the 2613 hits, 26 studies (cross-sectional, longitudinal and case-control studies) met the specified criteria and were included. We categorized the results into hormonal, respiratory, renal, cardiovascular, musculoskeletal health and general symptoms in informal e-waste workers. Exposure to e-waste was associated with altered lipid metabolism, thyroid hormonal imbalances, impaired fertility, renal dysfunction, increased prevalence of respiratory symptoms, asthma, cardiac arrhythmias, hypertension, musculoskeletal pain, injuries in up to 89% and skin disorders in up to 87.5-100% of e-waste workers. Due to inconsistent findings, weak associations or poor study quality, it has rarely been possible to establish a causal relationship between informal e-waste work and health effects, except for injuries or skin conditions. Besides high-quality studies, a collective national and international political focus on e-waste disposal is needed.

Late Adverse Effects after Treatment for Childhood Acute Leukemia.

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. CONCLUSION: It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care.

BdTTLL3B-mediated polyglycylation is involved in the spermatogenesis in Bactrocera dorsalis

Polyglycylation is a post-translational modification that generates glycine side chains in the C-terminal domains of both α- and β-tubulins. To date, the patterns and significance of polyglycylation across insect species remain largely unknown. The TTLL3B was thought to be a polyglycylase and be essential for polyglycylation in dipteran insects. In this study, the TTLL3B of Bactrocera dorsalis (BdTTLL3B) was identified and characterized. The BdTTLL3B expressed remarkably higher in adult males, especially in testes. The spatio-temporal patterns of polyglycylation were consistent with that of BdTTLL3B. Along with spermatogenesis, the intensity of polyglycylation was enhanced steadily and concentrated in elongated flagella. The expression of recombinant BdTTLL3B in Hela cells, which are genetically deficient in polyglycylation, catalyzed intracellular polyglycylation, validating the identity of BdTTLL3B as a polyglycylase. Knockout of BdTTLL3B significantly suppressed polyglycylation in testes and impaired male fertility, probably due to abnormal morphology of mitochondrial derivatives and over-accumulation of paracrystalline. Taken together, these findings indicated that the BdTTLL3B-mediated polyglycylation is involved in the spermatogenesis and play an important role in fertility of adult B. dorsalis. Therefore, the BdTTLL3B can be considered as a candidate target gene for the management of B. dorsalis, such as developing gene silencing/knockout-based sterile insect technology (SIT).

Follicular metabolic alterations are associated with obesity in mares and can be mitigated by dietary supplementation

Obesity is a growing concern in human and equine populations, predisposing to metabolic pathologies and reproductive disturbances. Cellular lipid accumulation and mitochondrial dysfunction play an important role in the pathologic consequences of obesity, which may be mitigated by dietary interventions targeting these processes. We hypothesized that obesity in the mare promotes follicular lipid accumulation and altered mitochondrial function of oocytes and granulosa cells, potentially contributing to impaired fertility in this population. We also predicted that these effects could be mitigated by dietary supplementation with a combination of targeted nutrients to improve follicular cell metabolism. Twenty mares were grouped as: Normal Weight [NW, n = 6, body condition score (BCS) 5.7 ± 0.3], Obese (OB, n = 7, BCS 7.7 ± 0.2), and Obese Diet Supplemented (OBD, n = 7, BCS 7.7 ± 0.2), and fed specific feed regimens for ≥ 6 weeks before sampling. Granulosa cells, follicular fluid, and cumulus-oocyte complexes were collected from follicles ≥ 35 mm during estrus and after induction of maturation. Obesity promoted several mitochondrial metabolic disturbances in granulosa cells, reduced L-carnitine availability in the follicle, promoted lipid accumulation in cumulus cells and oocytes, and increased basal oocyte metabolism. Diet supplementation of a complex nutrient mixture mitigated most of the metabolic changes in the follicles of obese mares, resulting in parameters similar to NW mares. In conclusion, obesity disturbs the equine ovarian follicle by promoting lipid accumulation and altering mitochondrial function. These effects may be partially mitigated with targeted nutritional intervention, thereby potentially improving fertility outcomes in the obese female.

Chronic exposure to tire rubber-derived contaminant 6PPD-quinone impairs sperm quality and induces the damage of reproductive capacity in male mice

It has been reported that N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q), a derivative of the tire antioxidant, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), exhibits acute toxicity towards organisms. However, the possible reproductive toxicity of 6PPD-Q in mammals has rarely been reported. In this study, the effects of 6PPD-Q on the reproductive toxicity of C57Bl/6 male mice were assessed after exposure to 6PPD-Q for 40 days at 4 mg/kg body weight (bw). Exposure to 6PPD-Q not only led to a decrease in testosterone levels but also adversely affected semen quality and in vitro fertilization (IVF) outcomes, thereby indicating impaired male fertility resulting from 6PPD-Q exposure. Additionally, transcriptomic and metabolomic analyses revealed that 6PPD-Q elicited differential expression of genes and metabolites primarily enriched in spermatogenesis, apoptosis, arginine biosynthesis, and sphingolipid metabolism in the testes of mice. In conclusion, our study reveals the toxicity of 6PPD-Q on the reproductive capacity concerning baseline endocrine disorders, sperm quality, germ cell apoptosis, and the sphingolipid signaling pathway in mice. These findings contribute to an enhanced understanding of the health hazards posed by 6PPD-Q to mammals, thereby facilitating the development of more robust safety regulations governing the utilization and disposal of rubber products.

Полисахариды базидиальных грибов повышают качество репродуктивных клеток быков при замораживании

The global decline in the animal and plant species diversity is among the key environmental problems of the modern world. One possible way to solve this problem is to develop advanced reproductive technologies using gametes to restore genetic diversity. Cryobanks play an important role in this. The traditional method of long-term storage of reproductive cells is their cryopreservation at –196оC using cryoprotective media based on synthesized substances (glycerin, dimethyl sulfoxide, etc.). The reason for searching new effective substitutes is cytotoxicity, impaired fertility and other disadvantages when using traditional cryoprotectors. In addition, it is relevant to expand the temperature range of biomaterial storage, in particular using the conditions of electric freezers. The wide range of biological effects of polysaccharides of basidiomycetes allowed us to make an assumption about the effectiveness of their use in the composition of the medium for cell cryopreservation. This paper presents the results of a comparative study of the effectiveness of polysaccharides of xylotrophic basidiomycetes in the composition of the medium for storage of the Holstein bull semen. The semen was frozen to –5оC and storaged at the specified temperature for 7 days in AndroMed® (Minitübe, Germany) – certified extender for freezing the semen of bulls and other ruminants. Additional introduction into its composition of polysaccharides from the basidiomycetes Hericium erinaceus BP16 / Ganoderma applanatum GA significantly improves the quality of reproductive cells in the used cryopreservation technology.