Longer / open ended questions

Question 1

You look at androgen having hyperinflammatory role, what if estrogen is protective?

Question 2

Could this be an effect of estradiol, since you are not preventing conversion of T into E?

Answer 2

Could be, estradiol seen to inhibit IL1 production in response to stimulation by LPS

Question 3

How are A exacerbating the IR, what mechanism?

Question 4

See a difference in proinflammatory response, but what if females have higher IL-10 (antiinflammatory response)

Answer 4

Looked at IL-10 in this same model and there was not difference detected BUT IL1Ra was increased in females,

Question 5

Are GBS bacteria affecting the BB directly and the developing brain?

Question 6

Are fetal cytokines affecting the BBB and triggering brain injuries?

Question 7

Characteristics of an ASD brain?

Answer 7

Increased astrocyte, activated microglia
Neuroinflammation

Question 8

How do you know IL1b is a key player?

Answer 8

Tested using IL1ra, blockade, alienates the specific role of IL-1, shown decreased inflammation in placenta correlating to less severe neurobehavioral deficits in offspring

Question 9

Does this model replicate in clinic GBS transmission?

Answer 9

No, does not replicate ascending route, by GBS colonising genital tract
A group developed a mouse model of GBS colonisation, but there were limitations
- differential exposure of fetuses closer to genital tract
- high litter variation

Question 10

What is the mechanism, how are androgens regulating IR?

Answer 10

modulate the innate IR through cell proliferation, cytokine secretion, toll like receptor expression

AR important for development of PMN precursor cells (AR KO mice- neutropenic, more susceptible to acute bacterial infection), AR important for development of PMN precusor cells impacts their proilferation activity

AR/androgen enhance granulocyte colony stimulating factor - activation of extracellular signal-regulated kinase 1/2 and through maintaing signal transducer and activator or transcription (STAT3) activity

Question 11

if you had more funding, what would you do?

Answer 11

“If I had additional funding, I would prioritize extending this work in two key directions.”

“First, translating these findings into human pregnancy. I would profile EV cargo—especially IL-1β and other inflammatory mediators—in placental or maternal plasma samples from GBS-positive pregnancies. This would test whether the EV signatures we identified in rats are conserved in humans, and whether they correlate with neonatal outcomes.”

“Second, I would expand into fetal sex comparisons. While this thesis focused on males due to their higher vulnerability, a direct comparison with female offspring would help determine whether the EV response, IL-1 signaling, or androgen sensitivity is sex-specific. This could clarify whether tailored interventions are needed.”
“First, I would translate our findings into human pregnancy.
Specifically, I’d profile EV cargo—especially IL-1β and S100 proteins—in placental tissue or maternal plasma from pregnancies complicated by GBS or chorioamnionitis. The goal would be to identify EV signatures that correlate with fetal or neonatal outcomes, potentially establishing early, non-invasive biomarkers.”