Atrial Fibrillation (AF) is the most common cardiac arrythmia in adults with likely sex-specific risk factors. Female sex hormones may be important in modulating risk for atrial fibrillation. We hypothesize that pregnancy and progesterone (P4), a hormone found in high levels during pregnancy with abrupt withdrawal immediately after parturition, modulates AF susceptibility in female goats. Cardiac specific TGF-?1 transgenic female goats and age-matched wild-type (WT) female goats were utilized. Pacemakers were implanted in all animals for continuous arrhythmia monitoring and AF inducibility. AF inducibility was evaluated using 5 separate 10 s bursts of atrial pacing (160 - 200 ms). In the first study, all animals were bred (n=12) via natural service and circulating progesterone levels and AF inducibility were monitored throughout gestation. In the second study, seven female goats were treated with high-dose exogenous oral P4 supplementation over a two-week period, and AF inducibility was assessed at baseline, during P4 supplementation and 48-hours following P4 supplementation. Serum P4 was measured using a chemiluminescent assay. Cardiac tissue was collected from both atria from goats in a high P4 state and a P4 withdrawal. RNA was extracted and gene expression analysis was ran on several genes related to AF. Atrial tissue was also During pregnancy, P4 levels increased compared to baseline with a sharp withdrawal during the post-partum period. This decrease in P4 levels post-parturition was associated with an increase in AF inducibility in both TGF-?1 and WT goats. Exogenous P4 supplementation increased circulating P4 compared to baseline with a decrease in P4 levels below baseline at 48-hours post supplementation. Consistent with our hypothesis and observations from the pregnancy studies, abrupt withdrawal of P4 was associated with increased AF inducibility when compared to baseline and P4 supplementation. Several genes were differentially expressed in the P4 withdrawal group compared to the high P4 group. CACN2D, CACNB2, and CAMK2D, all calcium related genes were significantly downregulated in the progesterone withdrawal (P4 WD) group when compared to the high progesterone (HIGH P4) group. These data support the hypothesis that progesterone is an important modulator of AF susceptibility in females. More specifically, abrupt reduction of progesterone significantly increases AF risk. Our gene expression data shows that P4 modulates calcium signaling in the atrium.

Author ORCID Identifier

Heloisa M. Rutigliano

Document Type




File Format


Publication Date



American Heart Association


Utah State University

Award Number

American Heart Association 19AIRE34470000

Award Title

Effects of Pregnancy and Progesterone on Atrial Fibrillation in a Transgenic Goat Model of Atrial Cardiomyopathy


Gene expression was assessed by quantitative real-time polymerase chain reaction using a high throughput microfluidics system (Biomark, Fluidigm)

Presence of immune cells positive for CD68 and MHC-II in cardiac tissue was assessed by immunohistochemistry assays.

Atrial fibrillation inducibility was assessed by burst pacing for 10 seconds at varying milliseconds (160-200) were performed: once at 200?S, two at 180?S, and two at 160?S. Inducibility was recorded after each burst.

qRT-PCR, immunohistochemistry, progesterone level and atrial fibrillation inducibility data are In .csv files.



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Animal Sciences | Dairy Science | Veterinary Pathology and Pathobiology


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.




Additional Files

Readme.txt (10 kB)
md5: 6f1068ec66e12d6386d5fe6df412da4c

Rutigliano_Project_AHA2018_IHC Staining data_CD68.csv (21 kB)
md5: c1d9fc53672ba3347258c26f1d862e77

Rutigliano_Project_AHA2018_RTPCRdata_P4II.csv (420 kB)
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Rutigliano_Project_AHA2018_P4data_OralP4.csv (1 kB)
md5: f81d374f374088697e540b848b8606ca

Rutigliano_Project_AHA2018_INDUCdata_CIDR.csv (17 kB)
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Rutigliano_Project_AHA2018_IHC Staining data_MHCII.csv (19 kB)
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Rutigliano_Project_AHA2018_RTPCRdata_P4I.csv (420 kB)
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Rutigliano_Project_AHA2018_INDUCdata_OralP4.csv (3 kB)
md5: 7e68217eb078888def0c86ec8869c54e

Rutigliano_Project_AHA2018_P4data_CIDR.csv (2 kB)
md5: f324607eb8cb112fd317d544ce04befb