Relationship between inhibition of mevalonate biosynthesis and reduced fertility in laying hens

The objective of the present study was to determine the effects of inhibition of mevalonate biosynthesis on fertility and embryonic survival in laying chickens. White Leghorn hens were fed for 5 weeks with a control diet alone or a diet supplemented with one of two concentrations (0.03 or 0.06%) of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors atorvastatin, lovastatin or simvastatin. The hens were artificially inseminated once a week and eggs that were not analysed for cholesterol content were incubated. When averaged across dietary groups and expressed as a percentage of all eggs incubated, the incidence of unfertilized eggs was 1.6% (controls), 29.1% (atorvastatin), 4.4% (lovastatin) and 7.9% (simvastatin). In contrast, with the exception of lower values for birds fed 0.06% atorvastatin, all groups had comparable hatchabilities of fertilized eggs. Hatchability of all eggs incubated was decreased in both atorvastatin groups compared with the other treatments. However, embryonic mortality of fertilized eggs was unaffected (P > 0.05) by diet. Compared with controls, maximum decreases in egg cholesterol of 46, 22 and 7% were obtained with atorvastatin, lovastatin and simvastatin, respectively. Although the overall correlation of egg cholesterol content with hatchability was high (r = 0.82), the hatch rate of eggs containing approximately 105 mg cholesterol ranged from 0 to 67%, indicating that egg cholesterol content was not the only factor influencing embryo survival. This is the first study to indicate that a mevalonate-derived product or products plays an important role in avian fertility. In addition, this work challenges the contention that virtually all of the cholesterol in chicken egg yolk is essential for embryonic development and survival.