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Lyme disease increases risk for multiple gynecological conditions

Hansen Colburn, P. S.; Blacker, G.; Galloway, S.; Feng, Q.; Padmanabham, P. S.; Pisani, G.; Lee, B. T.; Loeser, G.; Perez, M. W.; Liu, K.; Kuan, J.; von Saltza, E.; Strausz, S.; Mattei, L.; Nahass, G. R.; Kitjasateanphun, A.; Potula, H.-H. S.; Shoham, M. A.; Finngen, ; Mascetti, V. L.; Gars, E.; Ollila, H. M.; Bruner-Tran, K. L.; Weissman, I. L.; You, S.; Pollack, B.; Griffith, L.; Sinnott-Armstrong, N.; Tal, M. C.

2025-03-06 infectious diseases
10.1101/2025.03.03.25323258 medRxiv
Show abstract

Lyme disease (LD) is an illness caused by the spirochete Borrelia burgdorferi (B. burgdorferi). Borrelia is known to disseminate through organs, including the skin, joints, spinal cord, bladder, and heart, leading to Lyme arthritis, neuroborreliosis, and Lyme carditis. While previous studies have investigated the impact of LD on pregnancy in both mice and humans and have found the presence of B. burgdorferi in the uterus of mice, we studied the impact of LD on the non-pregnant female reproductive tract. We use a mouse model for LD and find an ongoing and severe infection of the reproductive tract of female mice, which persists up to 15-months post-inoculation. This infection results in uterine glandular cysts and endometrial hyperplasia as well as vaginal epithelial thickening, polymorphonuclear and mononuclear cell epithelial infiltration, and epithelial desquamation into the vaginal lumen. Strikingly, we find that age has an impact on the extent of gynecologic pathology such that aged female mice (1-year old) that are reproductively senescent have more gynecologic pathology with infection compared to young mice (15-weeks old) when infected for the same length of time. Using large-scale electronic healthcare record data, we report that LD additionally results in increased infection-associated risk of menorrhagia (1.5-fold), miscarriage (1.62-fold), uterine fibroids (1.42-fold), and endometriosis (1.93-fold). Underreporting of gynecological outcomes is pervasive throughout many different infectious diseases, and LD-associated gynecological pathologies may have been similarly underappreciated in the field. This work suggests that further study of the female reproductive tract and the effects of B. burgdorferi infection therein will help clarify and expand the knowledge of myriad LD outcomes. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=149 HEIGHT=200 SRC="FIGDIR/small/25323258v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@1eac89corg.highwire.dtl.DTLVardef@1189778org.highwire.dtl.DTLVardef@1807b22org.highwire.dtl.DTLVardef@140e91_HPS_FORMAT_FIGEXP M_FIG C_FIG

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