Biology subjects

Mulligan, M. E.

Publications and source records attributed to Mulligan, M. E..

2 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

Gut colonization by Bacteroides fragilis at juvenile age alters microbiota composition and accelerates type 1 diabetes progression in non-obese diabetic mice

Type 1 diabetes (T1D) in humans is associated with higher Bacteroidetes : Firmicutes ratio and higher abundance of Bacteroides genus members. Bacteroides fragilis (BF) is an integral component of the human colonic commensal microbiota. Here, we show that gut colonization of specific pathogen-free (SPF) non-obese diabetic (NOD) mice by BF at a juvenile age induces a pro-inflammatory immune response and accelerated disease progression. NOD mice born to BF-monocolonized parents not only showed rapid disease progression compared to germ-free (GF) controls but also preserved accelerated disease onset and higher disease incidence upon conventionalization, suggesting that BF contributes to a pro-inflammatory response and autoimmunity in T1D. Interestingly, we found that while gut microbiota composition was different in control and BF-colonized SPF mice, presence of BF alone could significantly impact the acquisition of microbial communities upon conventionalization of gnotobiotic mice. Bulk RNAseq analysis of colon tissues revealed profound differences in the gene expression pattern of GF and BF-monocolonized mice as well as their conventionalized counterparts, shedding light on the probable mechanisms contributing to accelerated disease onset in mice that are exposed to BF. We found that mucin production is downregulated and the abundance of mucin degraders such as Akkermansia muciniphila is profoundly lower in BF-colonized mice that are conventionalized. Overall, these studies demonstrate that early life acquisition of BF-like distal gut commensals could have profound modulatory effects on the eventual overall gut microbiota structure, immune function, and {beta}-cell specific autoimmune outcomes under genetic susceptibility.

immunology↗