Biology subjects

Patterson, A. L.

Publications and source records attributed to Patterson, A. L..

3 recordsLinked to original sources

bioRxiv2025

Oviduct fluid metabolic regulation of embryonic genome methylation

Adverse maternal health and lifestyle during pregnancy can program offspring susceptibility to noncommunicable diseases in adulthood. Oviduct fluid facilitates key preimplantation milestones, including embryonic genome activation. However, the regulatory mechanisms governing oviduct fluid composition, and the developmental consequences of its disruption, remain unclear. Capitalizing on conserved dynamics between human and bovine embryonic genome activation, we first established and characterized bovine oviduct epithelial organoids as a model system. Organoids were then exposed to {Delta}-tetrahydrocannabinol (THC) and cannabidiol (CBD) to test the hypothesis that exocannabinoids alter intra-organoid fluid composition. Treatment altered the organoid transcriptome and intra-organoid fluid metabolome, notably elevating 5'-deoxyadenosine levels. Subsequent embryo culture with 5'-deoxyadenosine during embryonic genome activation resulted in aberrant DNA methylation patterning - independently of direct THC and CBD exposure. These findings identify a novel, indirect, mechanism by which maternal exposures disrupt embryonic development through changes in oviductal metabolite secretions. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/659599v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@19ac750org.highwire.dtl.DTLVardef@935709org.highwire.dtl.DTLVardef@13723a8org.highwire.dtl.DTLVardef@105f473_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

cell biology↗

bioRxiv2024

Adenomyosis and fibrosis define the morphological memory of the postpartum uterus of dairy cows previously exposed to metritis.

Optimal reproductive success following parturition in lactating dairy cows is dependent upon adequate completion of uterine involution. Failure to resolve pathogenic bacterial contamination within the first week postpartum can lead to uterine disease (metritis). Metritis is associated with decreased fertility and a failure or delay to establish pregnancy. We hypothesized that the inflammation resulting from early postpartum metritis would be associated with long-term changes in uterine morphology due to impaired uterine involution within the first 30 days postpartum (dpp). First parity Holstein cows were diagnosed with or without metritis at 7-10 dpp and uterine tissue were analyzed at 30 (Exp. 1), or 80 and 165 (Exp. 2) dpp for the presence of abnormal morphology, including abnormal invasion of endometrial glands and stroma into the myometrium (adenomyosis) using immunohistochemistry for FOXA2 (uterine gland specific marker) and presence of late postpartum endometrial fibrosis using masons trichrome stain (MTS). Severity of adenomyosis was determined by the number and size of adenomyotic foci, distance of foci from the endometrium-myometrium interface (EMI), and degree of fibrosis (MTS stain intensity). The presence, size, and distance from the EMI of adenomyotic foci were greater later postpartum and in cows with early postpartum diagnosis of metritis. Endometrial fibrosis was greater at the stratum basalis (at EMI) compared to the stratum compactum endometrium (near lumen) for all Exp. 2 cows, but greater endometrial fibrosis (regardless of endometrial region) was observed in cows that were diagnosed with metritis. Taken together, these data indicate that early postpartum metritis is associated with long-term modifications to the postpartum uterine morphology, including aberrant endometrial invasion into the myometrium (adenomyosis) and increased pathological fibrogenesis, leading to the presence of late postpartum endometrial fibrosis (scar tissue). Additionally, increased collagen fiber at the EMI suggests a correlation between the development of adenomyosis and fibrosis, which could possibly result from sustained endometrial inflammation caused by uterine disease.

pathology↗

bioRxiv2018

Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids.

Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA. We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, Infinium MethylationEPIC array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria from fibroids, and further separated the fibroids into subtypes marked by MED12 mutation, HMGA2 activation (HMGA2hi) and HMGA1 activation (HMGA1hi). Upregulation of HMGA2 expression in HMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in the HMGA2 gene body. Furthermore, we found that expression of HOXA13 was highly upregulated in fibroids and that overexpression of HOXA13 in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.

physiology↗