Prenatal ethanol exposure disrupts the histological stages of fetal bone development

Abstract

Maternal ethanol intake during pregnancy results in impairments in general growth and skeletal development in the offspring. We have previously shown that ethanol retards skeletal ossification at doses lower than those that affect growth. Moreover skeletal sites vary in their sensitivity to ethanol effects, with more severe effects occurring in bones that undergo a greater proportion of their development in utero. Taken together, these data suggest that ethanol has specific effects on bone development, and that later stages in the ossification process may be particularly affected. Such effects could have important implications for the offspring's long-term bone health, as studies suggest that the intrauterine environment can program the skeleton. The present study examined the histological stages of bone development to determine if prenatal ethanol exposure alters the morphological development of the growth plate in the fetal rat. Rats were fed a liquid diet containing ethanol (Ethanol, E group), or without ethanol (Pair-Fed, PF, or Control, C groups) for 6 weeks: 3 weeks prior to breeding and during 3 weeks of pregnancy. Fetal tibiae were fixed, decalcified and stained for histological analysis on day 21 of gestation. Maternal ethanol intake resulted in a significant decrease in fetal total bone and diaphysis lengths, compared with tibiae from PF and C fetuses. Although the lengths of the epiphyses were not affected, ethanol disrupted the organization of the histological zones within the epiphyses. Prenatal ethanol exposure decreased the length of the resting zone, but increased the length of the hypertrophic zone. Enlargement of the hypertrophic zone is consistent with an effect of ethanol on the later stages of bone development; however ethanol's effect on the resting zone indicate that earlier stages of bone development may also be disrupted. The functional significance of these morphological changes to long-term bone health remains to be determined.

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

“…bone formation process, and reduce bone mineral content and bone density (Shankar et al, 2008). In early developmental stage, PEE restricts endochondral ossification process by inhibiting the development of resting zone in growth plate and by extending the length of HZ, thereby retards long bone development (Snow and Keiver, 2007). Consistent with this, we also found that PEE retards long bone development with enlarged HZ and shortened length of POC in fetus.…”

“…Previous studies in our laboratory showed that birth weight of PEE offspring was significantly lower than the control, while the IUGR rate was significantly higher, due to a high level of maternal glucocorticoid induced by PEE (Liang et al, 2011;Shen et al, 2014;Ni et al, 2015). Other studies also show that PEE could significantly reduce fetal body weight and body length as well as suppress longitudinal growth of fetal bone, and affect fetal bone mineralization (Simpson et A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 6 / 31 al., 2005;Snow and Keiver, 2007). The intrauterine growth deficits may affect postnatal bone development and persist into adulthood (Lanham et al, 2008).…”

Early life factors in the pathogenesis of osteoporosis

“…Undernourished pups, compared to the control group, showed adverse outcomes as demonstrated by several factors, including femur length (-47%; P < 0.001) and bone calcium (-67%; P < 0.001) and phosphorus (-46%; P < 0.001) contents. Using a different approach, Snow and Keiver [16] investigated the infl uence of maternal ethanol intake on offspring bone formation. In this Canadian study, 37 rats were divided into three groups.…”

Teratogenic Effects of Crude Ethanolic Root Bark and Leaf Extracts of Rauwolfia vomitoria (Apocynaceae) on the Femur of Albino Wistar Rat Fetuses

“…In a related study, Snow and Keiver [18] reported that prenatal ethanol exposure has effect on the resting zone of the developing bone indicating that earlier stages of bone development may also be disrupted. The decrease in the length of the resting zone increased the length of the hypertrophic zone and enlarged, which was consistent with an effect of ethanol on the later stages of bone development.…”