Semen analysis and fertility assessment in rabbits: statistical power and design considerations for toxicology studies.
Semen analysis is commonly used in evaluating human response to reproductive toxicants. Serial semen samples can be collected from rabbits and fertility assessed by artificial insemination, hence this species is potentially well suited for male reproductive toxicity studies that might be extrapolated to humans. However, the size and cost of rabbits often restricts the number of animals used, reducing the sensitivity of such studies. Therefore, it was of interest to optimize study design for semen analysis and fertility assessment in rabbits. Semen samples were collected weekly from sexually mature New Zealand white rabbits and a range of parameters was analyzed (Semen--pH, volume, osmolality; Sperm--number and concentration, morphology, viability, percentage motility, motion characteristics; Seminal plasma--fructose, citric acid, carnitine and protein concentrations, acid phosphatase activity). Male fertility was assessed by inseminating female rabbits with the minimum number of motile sperm required for normal fertility, determined to be one million. The within- and between-buck variabilities were determined for all parameters and used to calculate the statistical power of different study designs. The variability of sperm number and concentration was decreased when measured in four ejaculates collected within a short period of time rather than in a single ejaculate; this was not true of other endpoints measured. In addition, use of preexposure observations further increased the statistical power for all of the parameters. These data can be used to determine the optimum design for studies of male reproductive toxicity using rabbits, with particular regard to cost and the number of animals used.
Williams
J
J
Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Gladen
B C
BC
Schrader
S M
SM
Turner
T W
TW
Phelps
J L
JL
Chapin
R E
RE
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D002331:Carnitine / Q000032:analysis; D002951:Citrates / Q000032:analysis; D019343:Citric Acid; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005632:Fructose / Q000032:analysis; D007315:Insemination, Artificial; D008297:Male; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D012661:Semen / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure; D013223:Statistics as Topic
D002951:Citrates; D011506:Proteins; D019343:Citric Acid; D005632:Fructose; D000135:Acid Phosphatase; D002331:Carnitine