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Reproductive Endocrinology

SUN-161 - Gavage of Rats with the Human Duodenal Microbe Rothia Mucilaginosa Leads to Persistent Hyperandrogenism and Ovarian Histological Modifications

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Gabriela Leite, PhD: No financial relationships to disclose
Polycystic ovary syndrome (PCOS) is a major endocrine disorder of reproductive-age women. It has diverse clinical manifestations, including hyperandrogenism, ovarian dysfunction, and infertility. While the role of the gut microbiome in PCOS is poorly understood, we have previously shown that Rothia mucilaginosa, a Gram-positive bacterium found in the human duodenum, produces testosterone in vitro and induces a PCOS-like phenotype in rats, including altered estrous cycles, disrupted ovarian androgen pathways, and insulin resistance, independent of weight gain. Here, we further investigate whether R. mucilaginosa alters circulating androgen levels and ovarian histology in female rats.

Methods
Reproductive-age female Sprague Dawley rats were gavaged with 108 CFU/mL R. mucilaginosa (Rothia) or PBS (C1) daily for 4 weeks (gavage phase). After 4 weeks, half of the rats in each group were euthanized. The other half of the Rothia (Rothia/wo) and control (C2) groups were gavaged with PBS daily for another 4 weeks (prolonged phase), then euthanized. Estrous cycles were monitored daily via H&E-stained cells from vaginal lavages. Serum androgens (TT: total testosterone; A4: androstenedione) and progesterone (P4) levels at euthanasia were measured by LC-MS/MS. Ovaries were harvested, formalin fixed, and sectioned longitudinally. H&E-stained sections were analyzed by a specialized pathologist, and unstained sections were used to quantify androgen receptors (AR) by immunohistochemistry.

Results
After the initial gavage phase, there was no significant difference in circulating levels of TT and A4 between Rothia rats (n=40, TT=34.9±30.9 pg/mL; A4=35.4±41.4 pg/mL) and C1 (n=40, TT=26.1±4.7 pg/mL; A4=18.2±5.5 pg/mL, P=0.8 and P=0.6, respectively). No changes in P4 levels were seen (P=0.3). No ovarian histological abnormalities or AR expression changes were seen in Rothia, but 55% had disrupted estrous cycles with an arrested diestrus phase, vs. 30% in C1. During the prolonged phase, Rothia/wo still had disrupted estrous cycles (55% vs. 35% in C2), and now also had a higher number of active follicles (AF=1.76±0.93) and lower expression of AR (1.494e-007±5.015e-008) vs C2 (AF=1.2±1.03, P=0.015; AR=1.860e-007±9.287e-008, P=0.04). This was accompanied by higher circulating TT levels in Rothia/wo vs C2 (43.2±13.1 vs 25.6±13.0, P=0.034), which were also linked to increased AR expression (R=0.889, P=0.0019) and, likely, to a decreased number of corpora lutea (R=-0.771, P=0.07). C2 did not exhibit these traits.

Conclusion
Here, we show that daily gavage with the duodenal bacterium R. mucilaginosa can induce disrupted estrous cycles, hyperandrogenism, and increases in ovarian follicles which persist after discontinuation of microbial gavage. Ovarian functional studies, including assessment of follicular quality, are warranted to determine the impact on fertility, a key feature of PCOS.

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