Reproductive Endocrinology

ORF20-01 - Systems Immunogenetics Implicates TNF-Β-Induced Androgen-Independent AR Regulation in Modulation of PCOS Severity

Sunday, June 14, 2026

9:30 AM - 9:45 AM CT

Location: Room W179

Oral Abstract Presenter(s)

Dequina A. Nicholas, PhD (she/her/hers)

Assistant Professor
University of California Irvine
Irvine, CA, United States

Senior Author/Primary Investigator(s)

Dequina A. Nicholas, PhD (she/her/hers)

Assistant Professor
University of California Irvine
Irvine, CA, United States

Co-Author(s)

LV

Leandro M. Velez, PhD

University of California, Irvine
Irvine, California, United States
NU

Naveena Ujagar, n/a

University of California, Irvine
Irvine, United States
GD

Gabriela De Robles, M.S. (she/her/hers)

Graduate Student
UNIVERSITY OF CA - IRVINE
Irvine, California, United States
Christy M. Nguyen (she/her/hers)

PhD Candidate
UNIVERSITY OF CA - IRVINE
Irvine, CA, United States
KW

Kiara Dominique Wiggins, n/a

Graduate Student
UNIVERSITY OF CA - IRVINE
Irvine, California, United States
ZD

Zena Del Mundo, n/a

UNIVERSITY OF CALIF IRVINE
irvine, California, United States
SG

Siaje Gideon, n/a

University of California Irvine
Irvine, California, United States
JC

Jessica Cassin, PhD

UCSD
Irvine, California, United States
JK

Joshua Kim, n/a

University of California Irvine
Irvine, California, United States
NN

Nandini Naidu, n/a

University of California Irvine
Irvine, California, United States
JA

Julio Ayala Angulo, Graduate Student

Graduate student
UNIVERSITY OF CA - IRVINE
Irvine, CA, United States
BB

Benjamin Babaev, n/a

University of California Irvine
Bronx, New York, United States
RR

Rachel Ross, MD PhD

ALBERT EINSTEIN COLLEGE OF MEDICINE
Bronx, New York, United States
AK

Alexander Kauffman, PhD

University of California San Diego
La Jolla, California, United States
VT

Varykina Thackray, PhD

University of Calif, San Diego
La Jolla, California, United States
BB

Beata Banaszewska, n/a

Poznań University of Medical Sciences
Poznan, Poland
EW

Ewa Wysocka, n/a

Poznań University of Medical Sciences
Poznan, Poland
AD

Antoni Duleba, MD

University of CA, San Diego
La Jolla, California, United States
JC

Jessica Chan, MD

Cedars Sinai Medical Center
Los Angeles, California, United States

Senior Author/Primary Investigator(s)

MS

Marcus Seldin, PhD

University of California, Irvine
Irvine, United States

Disclosure(s):

Dequina A. Nicholas, PhD: No financial relationships to disclose

Christy M. Nguyen: No financial relationships to disclose

Polycystic ovary syndrome (PCOS) is a complex reproductive disorder with clear genetic susceptibilities that impact the heterogeneous clinical presentation of symptoms and severity through unknown mechanisms. Chronic inflammation is linked to PCOS, but a clear cause-and-effect relationship has yet to be established. This study employed a comprehensive systems immunology approach, utilizing a letrozole-induced PCOS mouse model to identify changes in inflammatory factors associated with PCOS symptoms. By analyzing immune cells and secreted cytokines from 22 different mouse strains, we identified TNF-β as a key cytokine associated with PCOS, regardless of genetic background. We confirmed elevated TNF-β transcripts in immune cells from women with PCOS. Importantly, we used a knockout of TCRα to show that functional T cells are a necessary component of driving pathologically elevated luteinizing hormone in letrozole-treated female mice. Finally, we demonstrate that TNF-β induces androgen-independent androgen receptor translocation in gonadotropic cells. These findings implicate T cell-derived TNF-β in the development of pathologically elevated LH in PCOS. TNF-β is therefore an attractive target for the future development of anti-inflammatory therapeutics to improve PCOS symptoms.