Periconceptional alcohol alters in vivo heart function in ageing female rat offspring: Possible involvement of oestrogen receptor signalling.

ABSTRACT

NEW FINDINGS: What is the central question of this study? What are the cardiovascular consequences of periconceptual ethanol on offspring throughout the lifespan? What is the main finding and its importance? It is shown for the first time that periconceptional alcohol has sex-specific effects on heart growth, with ageing female offspring exhibiting decreased cardiac output. Altered in vivo cardiac function in ageing female offspring may be linked to changes in cardiac oestrogen receptor expression. ABSTRACT Alcohol exposure throughout gestation is detrimental to cardiac development and function. Although many women decrease alcohol consumption once aware of a pregnancy, exposure prior to recognition is common. We, therefore, examined the effects of periconceptional alcohol exposure (PCEtOH) on heart function, and explored mechanisms that may contribute. Female Sprague-Dawley rats received a liquid diet ±12.5% v/v ethanol from 4 days prior to mating until 4 days after mating (PCEtOH). Cardiac function was assessed via echocardiography, and offspring were culled at multiple time points for assessment of morphometry, isolated heart and aortic ring function, protein and transcriptional changes. PCEtOH-exposed embryonic day 20 fetuses (but not postnatal offspring) had larger hearts relative to body weight. Ex vivo analysis of hearts at 5-7 months old (mo) indicated no changes in coronary function or cardiac ischaemic tolerance, and apparently improved ventricular compliance in PCEtOH females (compared to controls). At 12 mo, vascular responses in isolated aortic rings were unaltered by PCEtOH, whilst echocardiography revealed reduced cardiac output in female but not male PCEtOH offspring. At 19 mo, left ventricular transcript and protein for type 1 oestrogen receptor (ESR1), HSP90 transcript and plasma oestradiol levels were all elevated in female PCEtOH exposed offspring. Summarising, PCEtOH adversely impacts in vivo heart function in mature female offspring, associated with increased ventricular oestrogen-related genes. PCEtOH may thus influence age-related heart dysfunction in females through modulation of oestrogen signalling.