Inhibition of mevalonate biosynthesis in laying hens is associated with a marked increase in infertility

Inhibitors of HMG-CoA reductase (HMGR), the key enzyme of cholesterol (CHOL) biosynthesis, are effective egg CHOL-lowering agents when orally administered to laying hens. In a recent comparative study of three HMGR inhibitors [atorvastatin (AV), lovastatin (LV), and simvastatin (SV)], we observed a 47% reduction in the CHOL content of eggs from hens fed 0.06% AV vs. controls (105 vs. 202 mg CHOL/egg, respectively; Elkin et al., Atherosclerosis 134:123; 1997). Since an additional goal of that 5-wk study was to investigate the effects of HMGR inhibition on reproduction, all of the hens were artificially inseminated once weekly and all of the eggs not selected for CHOL analysis were incubated. Here, we report that although the overall correlation between egg CHOL content and hatchability was high (r = 0.82), the hatching rate of eggs containing ∼105 mg of CHOL was quite variable (67%, wk 2; 0%, wk 3; 20%, wk 4; and 19%, wk 5), suggesting that egg CHOL content was not the main factor influencing embryo survivability. Furthermore, the relative number of infertile eggs, expressed as a % of all nonhatching eggs, was 5.2-, 2.1-, and 3.0-fold greater than controls in hens fed AV, LV, and SV, respectively. The present work, which is the first to demonstrate a direct effect of mevalonate biosynthesis inhibition on fertility in avians, also disproved a long-standing dogma that all of the CHOL in chicken egg yolk is essential for embryonic development and survival.