TY - JOUR
T1 - A high-throughput method for unbiased quantitation and categorization of nuclear morphology
AU - Skinner, Benjamin Matthew
AU - Rathje, Claudia Cattoni
AU - Bacon, Joanne
AU - Johnson, Emma Elizabeth Philippa
AU - Larson, Erica Lee
AU - Kopania, Emily E.K.
AU - Good, Jeffrey Martin
AU - Yousafzai, Gullalaii
AU - Affara, Nabeel Ahmed
AU - Ellis, Peter James Ivor
N1 - Publisher Copyright:
© 2019 The Authors 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - The physical arrangement of chromatin in the nucleus is cell type and species-specific, a fact particularly evident in sperm, in which most of the cytoplasm has been lost. Analysis of the characteristic falciform ("hook shaped") sperm in mice is important in studies of sperm development, hybrid sterility, infertility, and toxicology. However, quantification of sperm shape differences typically relies on subjective manual assessment, rendering comparisons within and between samples difficult. We have developed an analysis program for morphometric analysis of asymmetric nuclei and characterized the sperm of mice from a range of inbred, outbred, and wild-derived mouse strains. We find that laboratory strains have elevated sperm shape variability both within and between samples in comparison to wild-derived inbred strains, and that sperm shape in F1 offspring from a cross between CBA and C57Bl6J strains is subtly affected by the direction of the cross. We further show that hierarchical clustering can discriminate distinct sperm shapes with greater efficiency and reproducibility than even experienced manual assessors, and is useful both to distinguish between samples and also to identify different morphological classes within a single sample. Our approach allows for the analysis of nuclear shape with unprecedented precision and scale and will be widely applicable to different species and different areas of biology.
AB - The physical arrangement of chromatin in the nucleus is cell type and species-specific, a fact particularly evident in sperm, in which most of the cytoplasm has been lost. Analysis of the characteristic falciform ("hook shaped") sperm in mice is important in studies of sperm development, hybrid sterility, infertility, and toxicology. However, quantification of sperm shape differences typically relies on subjective manual assessment, rendering comparisons within and between samples difficult. We have developed an analysis program for morphometric analysis of asymmetric nuclei and characterized the sperm of mice from a range of inbred, outbred, and wild-derived mouse strains. We find that laboratory strains have elevated sperm shape variability both within and between samples in comparison to wild-derived inbred strains, and that sperm shape in F1 offspring from a cross between CBA and C57Bl6J strains is subtly affected by the direction of the cross. We further show that hierarchical clustering can discriminate distinct sperm shapes with greater efficiency and reproducibility than even experienced manual assessors, and is useful both to distinguish between samples and also to identify different morphological classes within a single sample. Our approach allows for the analysis of nuclear shape with unprecedented precision and scale and will be widely applicable to different species and different areas of biology.
KW - fertility
KW - image analysis
KW - morphometrics
KW - rodents
KW - spermatogenesis
UR - http://www.scopus.com/inward/record.url?scp=85065572953&partnerID=8YFLogxK
U2 - 10.1093/biolre/ioz013
DO - 10.1093/biolre/ioz013
M3 - Article
C2 - 30753283
AN - SCOPUS:85065572953
SN - 0006-3363
VL - 100
SP - 1250
EP - 1260
JO - Biology of Reproduction
JF - Biology of Reproduction
IS - 5
ER -