Background: Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce.
Objectives: To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health.
Materials And Methods: Data from the FDA adverse event reporting system (FAERS) were analyzed (2010-2022). Disproportionality analyses were used to identify signals of each drug-adverse event pair associated with paternal drug exposure in a different hierarchical manner.
Results: Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam-small for dates baby and finasteride-cryptorchidism were particularly significant (reporting odds ratio, ROR > 800, N > 10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept-skeletal dysplasia, and tacrolimus-talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti-tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin.
Conclusions: This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases-abortion, diazepam-small for date baby, finasteride-cryptorchidism, etoposide and cisplatin-13 trisomy.
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http://dx.doi.org/10.1111/andr.13790 | DOI Listing |
Sci China Life Sci
January 2025
Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China.
Human mitochondrial DNA (mtDNA) harbors essential mutations linked to aging, neurodegenerative diseases, and complex muscle disorders. Due to its uniparental and haploid inheritance, mtDNA captures matrilineal evolutionary trajectories, playing a crucial role in population and medical genetics. However, critical questions about the genomic diversity patterns, inheritance models, and evolutionary and medical functions of mtDNA remain unresolved or underexplored, particularly in the transition from traditional genotyping to large-scale genomic analyses.
View Article and Find Full Text PDFBMC Biol
January 2025
Institute of Rare Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610000, Sichuan, China.
Background: The advancements in second-/third-generation sequencing technologies, alongside computational innovations, have significantly enhanced our understanding of the genomic structure of Y-chromosomes and their unique phylogenetic characteristics. These researches, despite the challenges posed by the lack of population-scale genomic databases, have the potential to revolutionize our approach to high-resolution, population-specific Y-chromosome panels and databases for anthropological and forensic applications.
Objectives: This study aimed to develop the highest-resolution Y-targeted sequencing panel, utilizing time-stamped, core phylogenetic informative mutations identified from high-coverage sequences in the YanHuang cohort.
PLoS One
January 2025
Institute for Human Development, Aga Khan University, Nairobi, Kenya.
Introduction: Children growing up in arid and semi-arid regions of Sub-Saharan Africa (SSA) face heightened risks, often resulting in poor developmental outcomes. In Kenya, the arid and semi-arid lands (ASAL) exhibit the lowest health and developmental indicators among children. Despite these risks, some children grow up successfully and overcome the challenges.
View Article and Find Full Text PDFClin Epigenetics
January 2025
Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology, University of Girona, 17003, Girona, Spain.
Recent studies support the influence of paternal lifestyle and diet before conception on the health of the offspring via epigenetic inheritance through sperm DNA methylation, histone modification, and small non-coding RNA (sncRNA) expression and regulation. Smoking may induce DNA hypermethylation in genes related to anti-oxidation and insulin resistance. Paternal diet and obesity are associated with greater risks of metabolic dysfunction in offspring via epigenetic alterations in the sperm.
View Article and Find Full Text PDFEpigenetics Chromatin
January 2025
Department of Maternal‑Fetal Biology, National Center for Child Health and Development, Tokyo, 157‑8535, Japan.
Background: DNA methylation plays a crucial role in mammalian development. While methylome changes acquired in the parental genomes are believed to be erased by epigenetic reprogramming, accumulating evidence suggests that methylome changes in sperm caused by environmental factors are involved in the disease phenotypes of the offspring. These findings imply that acquired sperm methylome changes are transferred to the embryo after epigenetic reprogramming.
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