Biology subjects

Rock, K. D.

Publications and source records attributed to Rock, K. D..

5 recordsLinked to original sources

bioRxiv2025

Exploratory Assessment of Preconception Phthalate Exposure on Fertility and Offspring Health in Mice

Infertility affects 10-15% of couples worldwide and is increasingly attributed to environmental exposures, particularly endocrine-disrupting chemicals (EDCs) such as phthalates. While gestational exposures are well studied, little is known about how preconception exposures influence fertility and offspring health. Phthalate exposure altered estrous cyclicity, with dams spending more time in proestrus and less in metestrus but did not significantly impact implantation or litter size. At E14.5, exposed fetuses exhibited increased bodyweights, accompanied by an expansion of the placental junctional zone in males. Altered bodyweight persisted into adulthood, however adulthood offspring displayed a reduction in bodyweight. RNA-sequencing revealed widespread transcriptional reprogramming in female placentas (518 DEGs) affecting immune regulation, steroid metabolism, and extracellular matrix remodeling, while male placentas exhibited only 9 DEGs but showed structural alterations. In offspring livers, transcriptomic shifts were sex-specific: females displayed downregulation of metabolic and immune genes (e.g., Cyp7a1, Mthfr, H2-DMB1), while males showed upregulation of immune and signaling genes (e.g., Elf4, Adm2, Ly6a). Collectively, these findings demonstrate that preconception phthalate exposure induces subtle but biologically meaningful maternal endocrine disruption, alters placental structure and function, and reprograms offspring growth and liver transcriptomes in a sex-specific manner. This work identifies the preconception window as a critical period of vulnerability for EDC impacts on reproductive success and intergenerational health.

pharmacology and toxicology↗

bioRxiv2025

Novel PFAS in Alligator Blood Discovered with Non-Targeted Ion Mobility-Mass Spectrometry

Per- and polyfluoroalkyl substances (PFAS) are a large and growing class of chemicals gaining global attention due to their persistence, mobility, and toxicity. Given the diverse chemical properties of PFAS and their varying distributions in water and tissue, monitoring of different matrices is critical to determine their presence and accumulation. Here, we used a platform combining liquid chromatography, ion mobility spectrometry, and high-resolution mass spectrometry for non-targeted analysis to detect and identify PFAS in alligator plasma from North Carolina (5 years, 2018-2022) and Florida (2021 only). Structures for 12 PFAS were elucidated, including 2 novel structures, and an additional 34 known PFAS were detected. Three of these compounds were previously unreported in environmental media. More PFAS were detected in North Carolina alligators and no novel PFAS were detected in Florida gators. Quantitative analysis of 21 of the known PFAS revealed that plasma concentrations did not change over the 5-year study. HighlightsO_LI46 PFAS were detected in blood plasma from North Carolina and Florida alligators using LC-IMS-HRMS C_LIO_LIStructures for 12 previously unreported PFAS were elucidated, including 2 novel structures C_LIO_LICape Fear River alligators had the most types and highest concentrations of PFAS C_LI

pharmacology and toxicology↗

bioRxiv2023

Quantitative Cross-Species Comparison of Serum Albumin Binding of Per- and Polyfluoroalkyl Substances from Five Structural Classes

Per- and polyfluoroalkyl substances (PFAS) are a class of over 8,000 chemicals that are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput, in vitro differential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this differential scanning fluorimetry assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H,1H,2H,2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of serum albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and perfluoroalkyl ether congeners bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive toxicity assessments for PFAS.

pharmacology and toxicology↗

bioRxiv2021

Colonization at birth with human CST IV cervicovaginal microbiota alters development and increases neonatal mortality in mice

Profound racial health disparities contribute to maternal-infant morbidity and mortality. An emergent risk factor is the maternal microbiota, whereby compositional alterations impact maternal health and offspring development during pregnancy and beyond. The presence of a nonoptimal CST IV cervicovaginal microbiota, more common in Black and Hispanic women, is associated with increased risk of preterm birth and adverse birth outcomes. Through examination of the biological mechanisms by which vertical transmission of microbiota from mother to offspring influences postnatal development, we found that exposing cesarean delivered mice with CST IV cervicovaginal microbiota from pregnant women produced lasting effects on offspring metabolic, immune, and neural outcomes. We then examined how compounding effects of a typical high-risk, proinflammatory in utero environment, characterized by a maternal obesogenic state and the presence of G. vaginalis, would affect the offspring response to CST IV microbial gut colonization. The resultant developmental immaturity, coupled with an exaggerated immune response induced by exposure to risk-associated maternal microbiota, resulted in a profound increase in neonatal mortality, supporting the critical importance of elucidating the multifactorial biological mechanisms involved in high-risk pregnancies. HighlightsO_LIGut colonization by nonoptimal human cervicovaginal microbiota had sex-specific effects on postnatal development. C_LIO_LIA high-risk in utero environment increased offspring mortality risk. C_LIO_LIHeightened innate immune response associated with mortality risk. C_LIO_LIDevelopmental immaturity, premature birth, and exposure to CST IV contribute to increased offspring mortality risk. C_LI

systems biology↗

bioRxiv2020

Heterozygous mutation of Sonic Hedgehog receptor (Ptch) drives cerebellar overgrowth and sex-specifically alters hippocampal and cortical layer structure, activity, and social behavior in female mice

Sonic hedgehog (SHH) signaling is essential for the differentiation and migration of early stem cell populations during cerebellar development. Dysregulation of SHH-signaling can result in cerebellar overgrowth and the formation of the brain tumor medulloblastoma. Treatment for medulloblastoma is extremely aggressive and patients suffer life-long side effects including behavioral deficits. Considering that other behavioral disorders including autism spectrum disorders, holoprosencephaly, and basal cell nevus syndrome are known to present with cerebellar abnormalities, it is proposed that some behavioral abnormalities could be inherent to the medulloblastoma sequalae rather than treatment. Using a haploinsufficient SHH receptor knockout mouse model (Ptch1+/-), a partner preference task was used to explore activity, social behavior and neuroanatomical changes resulting from dysregulated SHH signaling. Compared to wild-type, Ptch1+/- females displayed increased activity by traveling a greater distance in both open-field and partner preference tasks. Social behavior was also sex-specifically modified in Ptch1+/- females that interacted more with both novel and familiar animals in the partner preference task compared to same-sex wild-type controls. Haploinsufficency of PTCH resulted in cerebellar overgrowth in lobules IV/V and IX of both sexes, and female-specific decreases in hippocampal size and isocortical layer thickness. Taken together, neuroanatomical changes related to deficient SHH signaling may alter social behavior.

neuroscience↗