Biology subjects

Kalthur, G.

Publications and source records attributed to Kalthur, G..

2 recordsLinked to original sources

bioRxiv2024

Haploid Asexual Blastocyst Fitness Varies Across Mouse Strains Related to Efficiency of Exit From Totipotency

In vitro activation, both sexually and asexually, facilitates assessing the reproductive mode and fitness of mammalian oocytes. Herein, we present evidence of the enhancement of asexual haploid blastocyst fitness in one selectively-inbred Mus musculus population. We tracked sexually and asexually activated-oocytes as they exited totipotency and self-organized into blastocyst-stage embryos. We examined haploid and diploid parthenogenetic potential of activated-oocytes. Unexpectedly, [~]90% of selectively-inbred mouse oocytes that were asexually activated successfully generated haploid blastocysts, contrasting with [~]90% failure in randomly-outbred mice. Furthermore, by closely tracking the timeline of exit from totipotency, we propose a novel self-correcting totipotency clock, crucial for timely exit from totipotency and successful embryogenesis across mammals. Insufficiency in this self-correcting prerequisite, will alter the fitness landscape in different reproductive modes. Collectively, this work provides a quantitative framework to investigate the unknown disruptive evolutionary trajectories of reproductive modes and fitness of females in anisogamous species. HighlightsO_LISerendipitious discovery of disruptive evolution of haploid asexual reproductive mode and preimplantation embryogenetic fitness in FVB strain of mice. C_LIO_LINovel self-correcting totipotency clock regulates blastulation potential in mammals including humans and limits haploid asexual embryogenesis C_LIO_LIEvolution of haploid asexual reproductive mode and preimplantation embryogenetic fitness in FVB mouse is linked to a superior self-correcting totipotency clock lacking in other animals. C_LI Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/608531v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@12b9f77org.highwire.dtl.DTLVardef@f2759forg.highwire.dtl.DTLVardef@84029org.highwire.dtl.DTLVardef@1ac7f42_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Puberty Blocker and Aging Impact on Testicular Cell States and Function

Spermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as puberty blocker (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US. At the tissue level, we report mild-to-severe sex gland atrophy in PB treated children. We developed most extensive integrated single-cell RNA dataset to date (>100K single cells; 25 patients), merging both public and novel (52 month PB-treated) datasets, alongside innovative computational approach tailed for germ cells and evaluated the impact of PB and aging on SSC. We report novel constitutional ranges for each testicular cell type across the entire age spectrum, distinct effects of treatments on prepubertal vs adult SSC, presence of spermatogenic epithelial cells exhibiting post-meiotic-state, irrespective of age, puberty status, or PB treatment. Further, we defined distinct effects of PB and aging on testicular cell lineage composition, and SSC meiotogenetic state and function. Using single cell data from prepubertal and young adult, we were able to accurately predict sexual maturity based both on overall cell type proportions, as well as on gene expression patterns within each major cell type. Applying these models to a PB-treated patient that they appeared pre-pubertal across the entire tissue. This combined with the noted gland atrophy and abnormalities from the histology data raise a potential concern regarding the complete reversibility and reproductive fitness of SSC. The biorepository, data, and research approach presented in this study provide unique opportunity to explore the impact of PB on testicular reproductive health.

developmental biology↗