Assessing the effects of prenatal poly-drug exposure on fetal brain vasculature using optical coherence angiography

Abstract

Significance: Maternal exposure to drugs during pregnancy is known to have detrimental effects on the fetus. Alcohol (ethanol) and nicotine are two of the most commonly co-abused substances during pregnancy, and prenatal poly-drug exposure is common due, in part, to the prevalence of unplanned pregnancies. The second trimester is a critical period for fetal neurogenesis and angiogenesis. When drug exposure occurs during this time, fetal brain development is affected. Several behavioral, morphological, and functional studies have evaluated the changes in fetal brain development due to exposure to these drugs individually. However, research on the combined effects of ethanol and nicotine is far more limited, specifically on fetal vasculature changes and development.

Aim: We use correlation mapping optical coherence angiography (cm-OCA) to evaluate acute changes in fetal brain vasculature caused by maternal exposure to a combination of ethanol and nicotine.

Approach: Ethanol (16.6% v/v, at a dose of $0.75g/\mathrm{kg}$) and nicotine (at a dose of $0.1\mathrm{mg}/\mathrm{kg}$) were administered to pregnant mice after initial cm-OCA measurements in utero. Subsequent measurements were taken at 5-min intervals for a total period of 45 min. Results from these experiments were compared to results from our previous studies in which the mother was exposed to only ethanol (dose: $0.75g/\mathrm{kg}$) or nicotine (dose: $0.1\mathrm{mg}/\mathrm{kg}$).

Results: While results from exposure to ethanol or nicotine independently showed vasoconstriction, no significant change in vasculature was observed with combined exposure.

Conclusion: Results suggested antagonistic effects of ethanol and nicotine on fetal brain vasculature.

Keywords: brain vasculature; ethanol; murine fetus; nicotine; optical coherence angiography; varenicline.

Fig. 1

MIP of 3D cm-OCA images of fetal brain vasculature (a) before and (b) 45 min after maternal exposure to ethanol at a dose of $0.75\mathrm{g}/\mathrm{kg}$. The dashed yellow rectangle shows the main branch of the vessel on which quantifications were made. Figures adapted with permission.

Fig. 2

MIP of 3D cm-OCA images of fetal brain vasculature (a) before and (b) 45 min after maternal exposure to nicotine at a dose of $0.1\mathrm{mg}/\mathrm{kg}$. The dashed yellow rectangle shows the main branch of the vessel on which quantifications were made. Figures adapted with permission.

Fig. 3

MIP of 3D cm-OCA images of fetal brain vasculature (a) before and (b) 45 min after maternal exposure to a combination of ethanol and nicotine at a dose of $0.75\mathrm{g}/\mathrm{kg}$ and $0.1\mathrm{mg}/\mathrm{kg}$, respectively. The dashed yellow rectangle shows the main branch of the vessel on which quantifications were made.

Fig. 4

MIP of 3D cm-OCA images of fetal brain vasculature (a) before and (b) 45 min after maternal exposure to a combination of ethanol and varenicline at a dose of $0.75\mathrm{g}/\mathrm{kg}$ and $0.1\mathrm{mg}/\mathrm{kg}$, respectively. The dashed yellow rectangle shows the main branch of the vessel on which quantifications were made.

Fig. 5

Percentage change in VD after maternal exposure to the respective drugs every 5 min for 45 min. A, alcohol (ethanol); N, nicotine.

Fig. 6

Comparisons of the percentage change in VD at 45 min after maternal exposure to the respective drugs. The asterisk indicates statistical significance by a two-sided Mann–Whitney $U$ test. A, alcohol (ethanol); N, nicotine.