The effect of low-to-moderate-dose ethanol consumption on rat mammary gland structure and function and early postnatal growth of offspring

Abstract

High levels of alcohol consumption during pregnancy can lead to growth deficits in early postnatal life. However, the effects of low-to-moderate alcohol consumption during pregnancy are less clearly defined. The aim of this study was to determine whether low-to-moderate ethanol (EtOH) consumption throughout pregnancy in the rat alters maternal mammary gland morphology and milk protein levels, thereby affecting lactation and the growth of pups after birth. Sprague-Dawley rats were fed an ad libitum liquid diet ± 6% vol/vol EtOH throughout pregnancy. Mammary glands from dams were collected at embryonic day (E) 20 or postnatal day (PN) 1, and expression of milk proteins (α-lactalbumin, β-casein, and whey acidic protein) was examined. In addition, relative amounts of alveoli, lactiferous ducts, adipose tissue, and blood vessels were determined at PN1. A subset of rats gave birth, and offspring growth and milk intake were recorded. Mammary gland weight was unaltered by EtOH, and stereological analysis showed no differences in gland structure compared with control. Although there were no significant changes in mammary gland gene expression at the RNA level, protein levels of α-lactalbumin were increased and whey acidic protein were decreased by EtOH. Offspring of EtOH-fed dams consumed less milk than controls in the lactational period; however, this did not alter their early postnatal growth. Overall, it appears that low-to-moderate-dose prenatal EtOH exposure does not significantly alter mammary gland development but may alter the composition of the various proteins found within the milk in a manner that maintains overall pup growth.

Chronic low alcohol intake during pregnancy programs sex-specific cardiovascular deficits in rats

“…Sub-optimal blood pressure levels should be minimised to prevent hypotensive symptoms, particularly in the elderly who are vulnerable to falls [44]. On the other hand, the hypotensive phenotype in female ethanol-exposed offspring may buffer other hallmarks of disease previously reported in these offspring including altered glucose handling [22], and left ventricular hypertrophy and fibrosis [20] and thus could be construed as cardioprotective.…”

“…At 30 min, the BAC averaged ~ 0.03% and by 5 h was undetectable in most animals. This model of maternal EtOH exposure does not affect maternal nutrition or pregnancy outcomes, such as litter size or birth weight [22], and the level of alcohol exposure is equivalent to approximately two standard drinks within an hour in humans. We hypothesised that chronic low prenatal EtOH exposure would alter blood pressure profiles, endothelial vasodilator function and arterial stiffness in the offspring at 12 months of age, equivalent to middle age in humans.…”

Early‐lifeexposure to alcohol and the risk ofalcohol‐inducedliver disease in adulthood

“…Furthermore, elevated fasted plasma glucose and elevated insulin (Akison et al, 2019;Harper, Tunc-Ozcan, Graf, & Redei, 2014) occur in PAE rat offspring in adulthood. However, other preclinical studies did not observe that PAE affects glucose and insulin concentration (Amos-Kroohs, Nelson, Hacker, Yen, & Smith, 2018;Elton, Pennington, Lynch, Carver, & Pennington, 2002;Probyn et al, 2013). The fetal insulin hypothesis postulates that both birth weight and T2DM are two phenotypes of the same genotype (Shields, Freathy, & Hattersley, 2010).…”

Metabolic effects following periconceptional alcohol exposure in rat adult offspring: modulations by a postnatal western diet

“…Primarily, these models have shown that alcohol decreases nephron endowment and consequently increases blood pressure in the offspring following binge . Our lowmoderate model (6% EtOH v/v) showed that prenatal alcohol at these levels altered protein composition in the breast milk without affecting the mammary gland (Probyn et al, 2013b). Additionally, offspring exposed to a low-moderate dose of alcohol prenatally developed pulmonary fibrosis over time (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) Hence similar to our other alcohol models, the findings from this thesis should be seen as a part of a much larger picture.…”

“…Primarily, these models have shown that alcohol decreases nephron endowment and consequently increases blood pressure in the offspring following binge . Our lowmoderate model (6% EtOH v/v) showed that prenatal alcohol at these levels altered protein composition in the breast milk without affecting the mammary gland (Probyn et al, 2013b). Additionally, offspring exposed to a low-moderate dose of alcohol prenatally developed pulmonary fibrosis over time (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) months old males), which would compromise respiratory lung capacity (Probyn et al, 2013a); exhibited left ventricular hypertrophy and fibrosis associated with decreased maximal aortic flow velocity (8 months) (Nguyen et al, 2014); and induced anxiety-like behaviour via structural changes in the basolateral amygdala (8 and 15 months) (Cullen et al, 2013).…”