AUTHOR=Cheah Fook-Choe , Lai Chee Hoe , Tan Geok Chin , Swaminathan Anushia , Wong Kon Ken , Wong Yin Ping , Tan Tian-Lee 

TITLE=Intrauterine Gardnerella vaginalis Infection Results in Fetal Growth Restriction and Alveolar Septal Hypertrophy in a Rabbit Model

JOURNAL=Frontiers in Pediatrics

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.593802

DOI=10.3389/fped.2020.593802

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold><italic>Gardnerella vaginalis</italic> (GV) is most frequently associated with bacterial vaginosis and is the second most common etiology causing intrauterine infection after <italic>Ureaplasma urealyticum</italic>. Intrauterine GV infection adversely affects pregnancy outcomes, resulting in preterm birth, fetal growth restriction, and neonatal pneumonia. The knowledge of how GV exerts its effects is limited. We developed an <italic>in vivo</italic> animal model to study its effects on fetal development.</p><p><bold>Materials and Methods:</bold> A survival mini-laparotomy was conducted on New Zealand rabbits on gestational day 21 (28 weeks of human pregnancy). In each dam, fetuses in the right uterine horn received intra-amniotic 0.5 × 10<sup>2</sup> colony-forming units of GV injections each, while their littermate controls in the left horn received sterile saline injections. A second laparotomy was performed seven days later. Assessment of the fetal pups, histopathology of the placenta and histomorphometric examination of the fetal lung tissues was done.</p><p><bold>Results:</bold> Three dams with a combined total of 12 fetuses were exposed to intra-amniotic GV, and 9 fetuses were unexposed. The weights of fetuses, placenta, and fetal lung were significantly lower in the GV group than the saline-inoculated control group [mean gross weight, GV (19.8 ± 3.8 g) vs. control (27.9 ± 1.7 g), <italic>p</italic> &lt; 0.001; mean placenta weight, GV (5.5 ± 1.0 g) vs. control (6.5 ± 0.7 g), <italic>p</italic> = 0.027; mean fetal lung weight, GV (0.59 ± 0.11 g) vs. control (0.91 ± 0.08 g), <italic>p</italic> = 0.002. There was a two-fold increase in the multinucleated syncytiotrophoblasts in the placenta of the GV group than their littermate controls (82.9 ± 14.9 vs. 41.6 ± 13.4, <italic>p</italic> &lt; 0.001). The mean alveolar septae of GV fetuses was significantly thicker than the control (14.8 ± 2.8 μm vs. 12.4 ± 3.8 μm, <italic>p</italic> = 0.007). Correspondingly, the proliferative index in the interalveolar septum was 1.8-fold higher in the GV group than controls (24.9 ± 6.6% vs. 14.2 ± 2.9%, <italic>p</italic> = 0.011). The number of alveoli and alveolar surface area did not vary between groups.</p><p><bold>Discussion:</bold> Low-dose intra-amniotic GV injection induces fetal growth restriction, increased placental multinucleated syncytiotrophoblasts and fetal lung re-modeling characterized by alveolar septal hypertrophy with cellular proliferative changes.</p><p><bold>Conclusion:</bold> This intra-amniotic model could be utilized in future studies to elucidate the acute and chronic effects of GV intrauterine infections.</p>