Fig. 5
Csmd1 knockout ovaries show reduced morphologic quality and reproductive performance. a Barplot depicting proportions of infertile Csmd1 wildtype (WT) vs. knockout (KO) females. In the population sampled (n = 115 WT + 40 KO), Csmd1 genotype does not significantly predict infertility status in females (relative risk = 1.9, linear regression p-value > 0.05). b Probability density plot depicting female mating success over time, stratified by maternal genotype (black = wildtype females; red = knockout females; gray = all females). The distribution is periodic, recapitulating the periodicity of the mouse female estrous cycle. Knockout females require significantly more cycles to achieve pregnancy (βGT = 10.4, linear regression p-value = 0.01), with a small subset of females never achieving pregnancy. All statistical models account for confounders such as age, body weight, and male factors when appropriate (see Methods section). c Scatterplot depicting ovary weight versus age, stratified by genotype (black = wildtype females; red = knockout females). The fitted polynomial models are depicted as lines with color corresponding to genotype. Knockout females have significantly smaller ovaries than wildtype when controlling for age (quadratic regression p-value = 8.1 × 10−3). Gray hashed line demarcates rough onset of puberty in females. d Composition of follicles differs significantly between wildtype and knockout female ovaries, with significantly fewer pre-ovulatory follicles and significantly more atretic follicles in knockout (Hotelling t-test p-value = 3.5 × 10−3). Center line = median; hinges = upper and lower quartiles; whiskers = 1.5 × interquartile range. e Ovarian histology in a wildtype versus knockout female. Knockout ovaries were consistently enriched for foam cell macrophages, confirmed by Oil Red O stain in adjacent sections. We occasionally observed ovarian cysts in knockout females (asterisk). f Ovary from 336-day-old knockout showing extensive involvement of foam cells occupying 40% of the tissue (left). High magnification of ovary section from same animal; top shows multinucleated appearance of foam cells, bottom is Oil Red O stain of adjacent section (right). All scale bars = 100 μm. Source data are provided as a Source Data file
