Faculty Opinions recommendation of The androgen and progesterone receptors regulate distinct gene networks and cellular functions in decidualizing endometrium.

Abstract Particulate matter (PM) causes adverse developmental outcomes following prenatal exposure, but the underlying biological mechanisms remain uncertain. Here we elucidate the effects of diesel exhaust ultrafine particle (UFP) exposure during pregnancy on placental and fetal development. Time-mated C57Bl/6n mice were gestationally exposed to UFPs at a low dose (LD, 100 µg/m3) or high dose (HD, 500 µg/m3) for 6 hours daily. Phenotypic effects on fetuses and placental morphology at gestational day (GD) of 18.5 were evaluated, and RNA sequencing was characterized for transcriptomic changes in placental tissue from male and female offspring. A significant decrease in average placental weights and crown to rump lengths was observed in female offspring in the LD exposure group. Gestational UFP exposure altered placental morphology in a dose and sex-specific manner. Average female decidua areas were significantly greater in the LD and HD groups. Maternal lacunae mean areas were increased in the female LD group, whereas fetal blood vessel mean areas were significantly greater in the male LD and HD groups. RNA sequencing indicated several disturbed cellular functions related to lipid metabolism, which were most pronounced in the LD group and especially in female placental tissue. Our findings demonstrate the vulnerability of offspring exposed to UFPs during pregnancy, highlighting sex-specific effects and emphasizing the importance of mitigating PM exposure to prevent adverse health outcomes.

Download Full-text

LEC1 sequentially regulates the transcription of genes involved in diverse developmental processes during seed development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1707957114 ◽

2017 ◽

Vol 114 (32) ◽

pp. E6710-E6719 ◽

Cited By ~ 53

Author(s):

Julie M. Pelletier ◽

Raymond W. Kwong ◽

Soomin Park ◽

Brandon H. Le ◽

Russell Baden ◽

...

Keyword(s):

Transcription Factor ◽

Seed Development ◽

Gene Networks ◽

Target Genes ◽

Regulatory Elements ◽

Sequence Motifs ◽

In Planta ◽

Developmental Processes ◽

Distinct Gene ◽

Gene Sets

LEAFY COTYLEDON1 (LEC1), an atypical subunit of the nuclear transcription factor Y (NF-Y) CCAAT-binding transcription factor, is a central regulator that controls many aspects of seed development including the maturation phase during which seeds accumulate storage macromolecules and embryos acquire the ability to withstand desiccation. To define the gene networks and developmental processes controlled by LEC1, genes regulated directly by and downstream of LEC1 were identified. We compared the mRNA profiles of wild-type and lec1-null mutant seeds at several stages of development to define genes that are down-regulated or up-regulated by the lec1 mutation. We used ChIP and differential gene-expression analyses in Arabidopsis seedlings overexpressing LEC1 and in developing Arabidopsis and soybean seeds to identify globally the target genes that are transcriptionally regulated by LEC1 in planta. Collectively, our results show that LEC1 controls distinct gene sets at different developmental stages, including those that mediate the temporal transition between photosynthesis and chloroplast biogenesis early in seed development and seed maturation late in development. Analyses of enriched DNA sequence motifs that may act as cis-regulatory elements in the promoters of LEC1 target genes suggest that LEC1 may interact with other transcription factors to regulate distinct gene sets at different stages of seed development. Moreover, our results demonstrate strong conservation in the developmental processes and gene networks regulated by LEC1 in two dicotyledonous plants that diverged ∼92 Mya.

Download Full-text

Distinct gene networks modulate floral induction of autonomous maize and photoperiod-dependent teosinte

Journal of Experimental Botany ◽

10.1093/jxb/ery110 ◽

2018 ◽

Vol 69 (12) ◽

pp. 2937-2952 ◽

Cited By ~ 13

Author(s):

Mark A A Minow ◽

Luis M Ávila ◽

Katie Turner ◽

Elena Ponzoni ◽

Iride Mascheretti ◽

...

Keyword(s):

Gene Networks ◽

Floral Induction ◽

Distinct Gene

Download Full-text

Arsenic/interferon specifically reverses 2 distinct gene networks critical for the survival of HTLV-1-infected leukemic cells

Blood ◽

10.1182/blood-2002-09-2986 ◽

2003 ◽

Vol 101 (11) ◽

pp. 4576-4582 ◽

Cited By ~ 68

Author(s):

R. Nasr

Keyword(s):

Gene Networks ◽

Leukemic Cells ◽

Distinct Gene

Download Full-text

The Androgen and Progesterone Receptors Regulate Distinct Gene Networks and Cellular Functions in Decidualizing Endometrium

Endocrinology ◽

10.1210/en.2008-0356 ◽

2008 ◽

Vol 149 (9) ◽

pp. 4462-4474 ◽

Cited By ~ 100

Author(s):

Brianna Cloke ◽

Kaisa Huhtinen ◽

Luca Fusi ◽

Takeshi Kajihara ◽

Maria Yliheikkilä ◽

...

Keyword(s):

Cell Cycle ◽

Gene Networks ◽

Cell Cycle Regulation ◽

Embryo Implantation ◽

Fiber Formation ◽

Cellular Functions ◽

Endometrial Stromal Cells ◽

Cytoskeletal Organization ◽

Decidual Cells ◽

Cycle Regulation

Progesterone is indispensable for differentiation of human endometrial stromal cells (HESCs) into decidual cells, a process that critically controls embryo implantation. We now show an important role for androgen receptor (AR) signaling in this differentiation process. Decreased posttranslational modification of the AR by small ubiquitin-like modifier (SUMO)-1 in decidualizing cells accounted for increased responsiveness to androgen. By combining small interfering RNA technology with genome-wide expression profiling, we found that AR and progesterone receptor (PR) regulate the expression of distinct decidual gene networks. Ingenuity pathway analysis implicated a preponderance of AR-induced genes in cytoskeletal organization and cell motility, whereas analysis of AR-repressed genes suggested involvement in cell cycle regulation. Functionally, AR depletion prevented differentiation-dependent stress fiber formation and promoted motility and proliferation of decidualizing cells. In comparison, PR depletion perturbed the expression of many more genes, underscoring the importance of this nuclear receptor in diverse cellular functions. However, several PR-dependent genes encode for signaling intermediates, and knockdown of PR, but not AR, compromised activation of WNT/β-catenin, TGFβ/SMAD, and signal transducer and activator of transcription (STAT) pathways in decidualizing cells. Thus, the nonredundant function of the AR in decidualizing HESCs, centered on cytoskeletal organization and cell cycle regulation, implies an important role for androgens in modulating fetal-maternal interactions. Moreover, we show that PR regulates HESC differentiation, at least in part, by reprogramming growth factor and cytokine signal transduction.

Download Full-text