What is driving the global decline of human fertility? Need for a multidisciplinary approach to the underlying mechanisms

Frontiers in Reproductive Health, Journal Year: 2024, Volume and Issue: 6

Published: April 25, 2024

An intense period of human population expansion over the past 250 years is about to cease. Total fertility rates are falling dramatically all world such that highly industrialized nations, including China and tiger economies SE Asia, will see their populations decline significantly in coming decades. The socioeconomic, geopolitical environmental ramifications this change considerable invite a multidisciplinary consideration underlying mechanisms. In short-term, socioeconomic factors, particularly urbanization delayed childbearing powerful drivers reduced fertility. parallel, lifestyle factors as obesity presence numerous reproductive toxicants environment, air-borne pollutants, nanoplastics electromagnetic radiation, seriously compromising health. longer term, it hypothesized reduction family size accompanies demographic transition decrease selection pressure on high genes leading progressive loss fecundity. Paradoxically, uptake assisted technologies at scale, may also contribute fecundity by encouraging retention poor genotypes within population. Since rate appears be ubiquitous, public health implications for our species potentially devastating.

Language: Английский

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Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 93 - 93

Published: Jan. 17, 2025

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, non-coding RNA activity—are crucial both for spermatogenesis sperm maturation. However, oxidative stress, driven excessive reactive oxygen species, disrupts these processes, leading to impaired function male infertility. This disruption extends epigenetic resulting in abnormal gene expression chromatin remodeling that compromise genomic integrity fertilization potential. Importantly, oxidative-stress-induced alterations can be inherited, affecting the fertility offspring future generations. review investigates how stress influences regulation reproduction modifying RNAs, ultimately compromising spermatogenesis. Additionally, it discusses transgenerational implications disruptions their potential role hereditary infertility disease predisposition. Understanding mechanisms vital developing therapeutic strategies mitigate damage restore homeostasis germline. By integrating insights from molecular, clinical, research, this work emphasizes need targeted interventions enhance prevent adverse outcomes progeny. Furthermore, elucidating dose–response relationships between changes remains a critical research priority, informing personalized diagnostics interventions. In context, studies should adopt standardized markers damage, robust clinical trials, multi-omic approaches capture complexity Such rigorous investigations will reduce risk disorders optimize outcomes.

Language: Английский

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Single-cell transcriptomic atlas of the human testis across the reproductive lifespan

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Testicular aging is associated with declining reproductive health, but the molecular mechanisms are unclear. Here we generate a dataset of 214,369 single-cell transcriptomes from testicular cells 35 individuals aged 21–69, offering resource for studying and physiology. Machine learning analysis reveals stronger response in somatic compared to germ cells. Two waves aging-related changes identified: first peritubular donors their 30s, marked by increased basement membrane thickness, indicating priming state aging. In 50s, exhibit functional changes, including altered steroid metabolism Leydig immune responses macrophages. Further analyses reveal impact body mass index on spermatogenic capacity as age progresses, particularly after 45. Altogether, our findings illuminate alterations during testis relationship index, providing foundation future research potential diagnostic markers therapeutic targets. To enhance understanding human testis, authors provide map characteristics throughout lifespan. Using samples donors, they identify two examine interactions between index.

Language: Английский

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Single-cell RNA sequencing reveals transcriptomic landscape and potential targets for human testicular ageing

Human Reproduction, Journal Year: 2024, Volume and Issue: 39(10), P. 2189 - 2209

Published: Sept. 6, 2024

Abstract STUDY QUESTION What is the molecular landscape underlying functional decline of human testicular ageing? SUMMARY ANSWER The present study provides a comprehensive single-cell transcriptomic atlas testes from young and old humans offers insights into mechanisms potential targets for ageing. WHAT IS KNOWN ALREADY Testicular ageing known to cause male age-related fertility hypogonadism. Dysfunction cells has been considered as key factor DESIGN, SIZE, DURATION Human biopsies were collected three individuals perform RNA sequencing (scRNA-seq). results validated in larger cohort containing samples 10 donors donors. PARTICIPANTS/MATERIALS, SETTING, METHODS scRNA-seq was used identify gene expression signatures during Ageing-associated changes spermatogonial stem (SSCs) Leydig (LCs) analysed by set enrichment analysis immunofluorescent assays. Cell–cell communication performed using CellChat. MAIN RESULTS AND THE ROLE OF CHANCE men surveyed, revealing germline somatic niche cells. In-depth evaluation dynamics germ revealed that disruption base-excision repair pathway prominent characteristic SSCs, suggesting defective DNA SSCs may serve driver increased de novo mutations with age. Further ageing-associated transcriptional demonstrated stress-related cytokine pathways accumulate Age-related impairment redox homeostasis LCs identified pharmacological treatment antioxidants alleviated this cellular dysfunction promoted testosterone production. Lastly, our decreased pleiotrophin signalling contributing impaired spermatogenesis LARGE SCALE DATA processed data reported paper deposited at Genome Sequence Archive (https://ngdc.cncb.ac.cn/), under accession number HRA002349. LIMITATIONS, REASONS FOR CAUTION Owing difficulty collecting testis tissue, sample size limited. in-depth mechanistic studies are warranted future. WIDER IMPLICATIONS FINDINGS These findings provide understanding cell type-specific resolution, suggest therapeutic be leveraged address FUNDING/COMPETING INTEREST(S) This work supported National Key Research Development Program China (2022YFA1104100), Natural Science Foundation (32130046, 82171564, 82101669, 82371611, 82371609, 82301796), Guangdong Province, (2022A1515010371), Major Project Medical Technology Center Health Planning Commission, (HDSL202001000), Open NHC Laboratory Male Reproduction Genetics (KF202001), Province Regional Joint Fund-Youth Fund (2021A1515110921, 2022A1515111201), Postdoctoral (2021M703736). authors declare no conflict interest.

Language: Английский

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Predictive factors for spontaneous conception in women with moderate and severe endometriosis following operative laparoscopy: A cohort study

European Journal of Obstetrics & Gynecology and Reproductive Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children

Reproduction, Journal Year: 2024, Volume and Issue: 167(6)

Published: March 12, 2024

In light of the increasing age first-time fathers, this article summarizes current scientific knowledge base on reproductive aging in male, including sperm quality and health impacts for offspring. The emerging role NAD decline is highlighted.

Language: Английский

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Melatonin as a natural anti-inflammatory and anti-oxidant therapy in the testis: a focus on infertility and aging

Biology of Reproduction, Journal Year: 2024, Volume and Issue: unknown

Published: June 12, 2024

Abstract Melatonin is a pineal hormone that regulates testicular activity (i.e., steroidogenesis and spermatogenesis) through two complementary mechanisms, indirect effects exerted via the hypothalamic–adenohypophyseal axis direct actions take place on different cell populations of male gonad. The increased age testis general mechanisms involved in pathology leading to infertility are still only poorly understood. However, there growing evidence link aging idiopathic local inflammatory oxidative stress events. Because literature data strongly indicate melatonin exhibits anti-inflammatory anti-oxidant properties, this review focuses potential benefits by indoleamine at level reproductive fertility aging. Taking into account supplementation function currently being investigated, overview covers not promising prospects but also many questions concerning future therapeutic value as an anti-aging drug well management cases for which no medical treatments available.

Language: Английский

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SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the aging mouse testis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Reproductive aging is an increasing health concern affecting family planning and overall well-being. While extensively studied in females, the mechanisms driving male reproductive remain largely unexamined. Here we found that mammalian Sirtuin 7 (SIRT7) sustains spermatogenesis age-dependent manner through control of histone 3 lysine 36 acetylation (H3K36ac). SIRT7 deficiency mice resulted increased levels H3K36ac spermatogonia spermatocytes. In a germ cell line, disrupted nucleosome stability vulnerability to genotoxic stress. Importantly, undifferentiated spermatogonia, which are required for continuous sperm production, decreased prematurely Sirt7 -/- showed genome damage accumulation. These changes were concurrent with defects homologous chromosome synapsis partial meiotic arrest. Taken together, our results indicate connects epigenetic regulation long-term cells, ensuring steady-state during lengthy lifespan.

Language: Английский

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Longitudinal trends and correlation between autism spectrum disorder prevalence and sperm quality parameters (2000–2024): a comprehensive statistical analysis

Frontiers in Reproductive Health, Journal Year: 2024, Volume and Issue: 6

Published: Aug. 22, 2024

Introduction Over the past few decades, there has been growing concern about concurrent trends of increasing Autism Spectrum Disorder (ASD) prevalence and declining sperm quality. These represent significant public health challenges that warrant thorough investigation their underlying causes implications. Objectives The primary objectives this study are to analyze in ASD quality parameters from 2000 2024, assess statistical significance effect size these trends, explore potential correlations between parameters, identify predictors among influence prevalence. Methods This employed a longitudinal approach using multiple regression, time series analysis, ANOVA, Principal Component Analysis (PCA), hierarchical clustering, logistic cross-correlation analysis. Data on were sourced CDC Developmental Disabilities Monitoring Network, while data collected various published studies. Results findings reveal negative associations such as concentration motility, suggesting better is linked lower rates. Conversely, like DNA fragmentation (SDF), volume ejaculate, pH level, semen viscosity show positive with prevalence, indicating higher values correlate Conclusion highlights importance maintaining reproductive potentially mitigate risk calls for further research elucidate mechanisms driving trends. support hypothesis factors play crucial role etiology suggest biological markers assessing risk.

Language: Английский

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Environmental and Genetic Traffic in the Journey from Sperm to Offspring

Biomolecules, Journal Year: 2023, Volume and Issue: 13(12), P. 1759 - 1759

Published: Dec. 7, 2023

Recent advancements in the understanding of how sperm develop into offspring have shown complex interactions between environmental influences and genetic factors. The past decade, marked by a research surge, has not only highlighted profound impact paternal contributions on fertility reproductive outcomes but also revolutionized our comprehension unveiling parental factors sculpt traits successive generations through mechanisms that extend beyond traditional inheritance patterns. Studies are more susceptible to factors, especially during critical phases growth. While these broadly detrimental health, their effects acute periods. Moving immutable nature genome, epigenetic profile cells emerges as dynamic architecture. This flexibility renders it disruptions. primary objective this review is shed light diverse processes which agents affect male capacity. Additionally, explores consequences interactions, demonstrating can reverberate offspring. It encompasses direct changes well broad spectrum adaptations. By consolidating current empirically supported research, offers an exhaustive perspective interwoven trajectories environment, genetics, epigenetics elaborate transition from

Language: Английский

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