Abstract
Laboratory animal research is an important contributor to both human and animal medicine. Currently, there is extensive use of cynomolgus monkeys (Macaca fascicularis) in pathology and toxicology research. The purpose of this study was to define reference values for absolute and percentage organ weights in M fascicularis of different ages and sex. Organ weights were obtained from necropsies of 1022 cynomolgus monkeys at the Wake Forest School of Medicine from 1997 to 2018. Distributions of absolute and percentage weights for each organ were described; sex and age groups were compared using analysis of variance. Age effects on percentage of body weights for each organ were analyzed within each sex. Diet effects were also analyzed. This evaluation showed that male body weights and absolute organ weights were greater for all age groups; however, female organ to body weight percentages were greater for most organs. Percentage of organ weight to body weight declined for the adrenals, brain, lung, thyroid and thymus during maturation, whereas percentage weight of pancreas, prostate, testes, and uterus increased. Animals consuming a high-fat, Western-type diet had a lower body weight than animals consuming a carbohydrate-rich chow diet. This information will be useful for further toxicology and pathology studies concerning cynomolgus monkeys.
Keywords: organ weights, nonhuman primate, cynomolgus, pathology, sex differences, development
Introduction
Due to the genetic and physiologic similarity among primates, nonhuman primates are often used in a laboratory research setting as models.1 Currently, there is extensive use of cynomolgus monkeys (Macaca fascicularis) in research.2,3 So far, these monkeys have been used to study drug efficacy, toxicology, immunology, xenotransplantation, infectious disease, metabolic disease, degenerative disorders, and many other humanrelated issues in biomedical research.4–8
Normal organ weights for a species are used as a reference point when studying pathology. There is a need for species-specific guidelines concerning reference points in research.9 In addition, organ weights are helpful tools for diagnosis during necropsy.10 While there are papers concerning normal organ weights for Papio hamadryas (baboons),11,12 Macaca mulatta (rhesus macaques),13 Macaca arctoides (stump-tailed macaques),14 and Homo sapiens (humans),15–19 there is currently no large-scale published reference for organ weights of cynomolgus monkeys. Therefore, we sought to describe and compare organ weights in M fascicularis by age group and by sex. We hypothesized that males would have greater organ weights than females, as seen in other studies with nonhuman primates.11–14 We also hypothesized that some organ weights would be greater in older age groups throughout life (spleen, heart, pancreas, liver, kidneys),14 while others would plateau once a certain age was reached (brain, lungs, adrenal glands, thyroid, pituitary), indicating different growth patterns for these organs.
Because the population examined included both animals fed standard laboratory diets and custom-formulated Western-type diets, the effects of diet were examined in a subset of animals.
Materials and Methods
Animal Characteristics
This study used data collected over a 20-year period to retrospectively compare organ weights of cynomolgus monkeys in relation to age, sex, and diet. These data were collected via necropsy records from 1022 cynomolgus monkeys at the Wake Forest School of Medicine Clarkson Research Campus. Records of animals with insufficient data (e.g., age or sex was unknown) were eliminated from the study. The geographical origins of these monkeys were primarily Indonesia (908), with fewer animals from China (62), Mauritius (18), Malaysia (24), Vietnam (4), the Philippines (4), and Cambodia (2). Records for monkeys were included in the study if they were cynomolgus macaques, and their age, organ weights, and sex were known.
Ages were split into categories which were defined as follows: infant (0–30 days), juvenile (31 days to 2.5 years), peripubertal (>2.5–4 years), young adult (>4 to 9.5 years), adult (>9.5 to 20 years), and aged (>20 years) (Tables 1 and 2). The ages of all monkeys included in the study were either known or determined via dentition.20,21 The age of 4 years used for the peripubertal-to-young adult distinction was chosen to approximate the age of sexual maturity.22–24 The age of 9.5 years for the young adult-to-adult distinction was chosen based on developmental landmarks including long bone physeal closure, eruption of the third molar “wisdom” teeth (10/22/2015, written communication, C. Lees, DVM, Wake Forest School of Medicine), and peak bone mass which occurs at 9 years of age in females.25
All studies from which these samples were taken were conducted with review and approval by the Wake Forest Institutional Animal Care and Use committee. Wake Forest is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) and registered with the United States Department of Agriculture (USDA) to conduct research in laboratory animals.
Wake Forest University has an Assurance in the Office for Protection from Research Risks (OPRR), Office of the Director, NIH, and accepts responsibility for the humane care and use of animals (OPRR #A-3391–01). The institution complies with the “Principles for Use of Animals,” the “Guide for the Care and Use of Laboratory Animals,” and all provisions of the Animal Welfare Act.
All animals in this study were either naive subjects from our breeding colony, from holding protocols, or from control groups of long-term studies reported previously.26–30
Roughly 70% of the monkeys were socially housed in pens, with the others in individual cages or outdoor corrals. Approximately 10% to 20% of the monkeys had pedigrees that traced their lineage. A variety of diets were fed, most often monkey chow (Monkey Diet 5037 or 5045, LabDiets, St. Louis, MO) or a Western diet (TAD Primate Diet 5L0P, LabDiets, St. Louis, MO; or custom-formulated diets). For analysis of dietary effects, a subset of 634 control animals in long-term studies was used, for which a specific diet was fed for least 1 year (Table 3).
Organ Weights
Organ weights for the adrenal glands, brain, gonads, heart, kidneys, liver, lungs, pancreas, pituitary, prostate, spleen, thymus, thyroids, and uterus were measured on a calibrated electronic digital scale, weighed to 100th of a gram, and recorded on a standardized worksheet. Paired organs were weighed separately as is designated on our standardized necropsy forms due to the presence of one-sided lesions, thus they have been kept separate for our following analysis. Quality assurance checks were done for the calibration of these scales weekly (Mettler Toledo PB602-S, Fisher Scientific, Columbus, OH; or Ohaus Adventurer AX422/E, Fisher Scientific, Parsippany, NJ). The standardized worksheet was transcribed into digital form in an online database and audited for quality assurance.
Regarding dissection of the organs: The brain was severed at the foramen magnum and the dura was removed. The heart was severed at the base of the aorta just below the brachiocephalic trunk and the pericardium was removed. The aortic arch was not included in heart weight, however, epicardial fat was included. Sixty percent of hearts were weighed after isolated perfusion fixation with 10% neutral buffered formalin. Lungs were separated from the trachea and cut at the main stem bronchi; the 3 left lobes were weighed together, as were the 4 right lobes including the accessory lobe. Pituitary dura and sella turcica were removed. For all visceral organs such as pancreas, spleen, kidneys, liver, and adrenal glands, all extraneous fat and vasculature were removed. The renal capsule was also removed and ureters were cut level with the renal pelvis. The pancreas was dissected free of the stomach and duodenum. When the thymus could be visually distinguished from fat, the fat was removed; however, fat may have been included due to its anatomic location. Testes were weighed with the epididymides removed. The prostate included cranial and caudal lobes and the prostatic urethra. Uteri were separated from the cervix by transection at the isthmus and cut free of the oviducts and ligaments.
Statistics
Obvious data errors (e.g., order-of-magnitude errors or zero values for weights) were removed from the data set. Organs that were affected by neoplasms, abscesses, cysts, or any other gross abnormalities that would significantly affect the organ weight were excluded (n = 10). Additional outliers were removed if they were greater than three times the interquartile range above the 75th percentile or three times the interquartile range below the 25th percentile (n = 254 data points, or 1.5% of the 16,704 data points). Data were examined using scatter plots to show the relationship between each organ, age, and sex. Best-fit lines were generated for each organ across the lifespan as continuous functions to visualize trends and maximize correlation coefficients (R2), using Excel Solver add-in power functions of the form y = axb; this provided the best fit for most tissues; some tissues (e.g., ovaries, uterus, testes, and prostate) were best fit by a logistic function. Percentage of total body weight was calculated for each organ studied and descriptive statistics (means, standard deviations, and percentiles) were used to summarize data by age group and sex. Throughout, the term “percentage weight” refers to organ weight as a percentage of body weight. Absolute and percent weights for sex and age groups were compared using two-way analysis of variance (ANOVA). Percent body weights for each organ were also analyzed with one-way ANOVA within each sex. Diet effects on body weight were tested using two-way ANOVA by sex and diet. Age and sex, as well as sex and diet, were tested for interactive effects, using a general linear model. Left-right differences in paired organs were compared using a two-tailed paired t test. Subspecies comparisons of body weight and percent organ weights were made between Indonesian, Chinese, Mauritian, and Malaysian animals, using a one-way ANOVA subspecies within each sex, including only young adult and adult animals. All statistical tests were done using JMP (version 14, SAS Institute, Cary, NC). A two-sided alpha level of 0.05 was used to indicate statistical significance. Data in the text are expressed as mean ± standard deviation.
Results
Animal demographics are shown in Tables 1 and 2. The majority of the monkeys in this study were adult females (74.3%). Absolute body and organ weight data by age and sex are shown graphically in Figures 1, 2, 3, 4, and 5. Organ weights expressed as a percentage of body weight by age group and sex are shown in Figures 6, 7, 8, and 9. Distributions of weights by age group and sex are summarized in Tables 4, 5, 6, 7, 8, and 9. For all measures of absolute weights, variation was substantial. Subspecies effects are shown in Table 10. Dietary effects are shown for body weight and all organs in Table 11. Major findings are summarized briefly below.
Table 1.
Male cynomolgus subjects sorted by age category.
| Age category | N | Average age (years) | Standard deviation |
|---|---|---|---|
|
| |||
| Infants (0–30 days) | 11 | n/a | ±0.01 |
| Juvenile (31 days to 25 years) | 28 | 1.11 | ±0.71 |
| Peripubertal (2.5–4 years) | 18 | 3.17 | ±0.75 |
| Young Adult (4–9.5 years) | 27 | 6.78 | ±1.07 |
| Adult (9.5–20 years) | 99 | 16.78 | ±2.38 |
| Aged (>20 years) | 79 | 23.00 | ±2.76 |
| Total | 262 | ||
Table 2.
Female cynomolgus subjects sorted by age category.
| Age category | N | Average age (years) | Standard deviation |
|---|---|---|---|
|
| |||
| Infants (0–30 days) | 14 | 0.01 | ±0.01 |
| Juvenile (31 days to 2.5 years) | 36 | 1.16 | ±0.75 |
| Peripubertal(2.5–4 years) | 22 | 3.29 | ±0.90 |
| Young Adult (4–9.5 years) | 42 | 8.06 | ±1.18 |
| Adult (9.5–20 years) | 466 | 14.65 | ±2.97 |
| Aged (>20 years) | 179 | 22.75 | ±2.54 |
| Total | 759 | ||
Figure 1.
Absolute body weight (kg) versus age (in years) by sex (N = 992).
Figure 2.
Absolute weight (grams) versus age (in years) scatter plots for select single and paired organs studied by sex (N = 955 for right adrenal, 959 for left adrenal, 970 for left kidney, 966 for right kidney, 969 for brain, and 975 for heart).
Figure 3.
Absolute weight (grams) versus age (in years) scatter plots for select single and paired organs studied by sex (N = 924 for left lung, 916 for right lung, 273 for left ovary, 272 for right ovary, 968 for liver, and 926 for pancreas).
Figure 4.
Absolute weight (grams) versus age (in years) scatter plots for select single and paired organs studied by sex (N = 869 for pituitary, 189 for prostate, and 949 for spleen).
Figure 5.
Absolute weight (grams) versus age (in years) scatter plots for select single and paired organs studied by sex (N = 227 for left testis, 225 for right testis, 931 for left thyroid, 928 for right thyroid, 192 for thymus, and 572 for uterus).
Figure 6.
Bar graph of mean organ weight as a percentage of body weight by age category. Statistical significance is relative to the adult group of the same sex. *P < .05. **P < .0001 from analysis of variance. Error bars represent 1 standard error of the mean. For paired organs, statistical significance is comparing subjects to the adult group of the same sex according to anatomical position (i.e., left or right).
Figure 7.
Bar graph of mean organ weight as a percentage of body weight by age category. Statistical significance is relative to the adult group of the same sex. *P < .05. **P < .0001 from analysis of variance. Error bars represent 1 standard error of the mean. For paired organs, statistical significance is comparing subjects to the adult group of the same sex according to anatomical position (i.e., left or right).
Figure 8.
Bar graph of mean organ weight as a percentage of body weight by age category. Statistical significance is relative to the adult group of the same sex. *P < .05. **P < .0001 from analysis of variance. Error bars represent 1 standard error of the mean. For paired organs, statistical significance is comparing subjects to the adult group of the same sex according to anatomical position (i.e., left or right).
Figure 9.
Bar graph of mean organ weight as a percentage of body weight by age category. Statistical significance is relative to the adult group of the same sex. *P < .05. **P < .0001 from analysis of variance. Error bars represent 1 standard error of the mean.
Table 4.
Infant absolute body weight (kg) and absolute organ weight (g) distribution.
| Body weight or organ weighed | Male | Female | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||||
| N | Min | 25% | 50% | 75% | Max | Mean ± SD | N | Min | 25% | 50% | 75% | Max | Mean ± SD | |
|
| ||||||||||||||
| Body weight | 11 | 0.17 | 0.20 | 0.33 | 0.38 | 0.61 | 0.32 ±0.12 | 14 | 0.11 | 0.20 | 0.24 | 0.32 | 0.38 | 0.25 ± 0.08 |
| Left adrenal | 6 | 0.04 | 0.10 | 0.17 | 0.31 | 0.35 | 0.19 ± 0.12 | 12 | 0.02 | 0.08 | 0.13 | 0.17 | 0.26 | 0.13 ± 0.07 |
| Right adrenal | 6 | 0.04 | 0.09 | 0.19 | 0.23 | 0.24 | 0.16 ± 0.08 | 11 | 0.02 | 0.07 | 0.09 | 0.11 | 0.17 | 0.09 ± 0.04 |
| Brain | 7 | 38.86 | 41.82 | 44.00 | 45.70 | 45.76 | 43.27 ± 2.53 | 13 | 19.69 | 29.92 | 33.44 | 39.20 | 49.20 | 33.65 ± 7.81 |
| Heart | 11 | 0.86 | 1.42 | 1.76 | 2.96 | 4.10 | 2.21 ± 1.06 | 13 | 0.70 | 1.35 | 1.69 | 2.13 | 3.24 | 1.80 ± 0.63 |
| Left kidney | 9 | 0.65 | 0.69 | 1.03 | 1.39 | 1.75 | 1.05 ± 0.41 | 12 | 0.31 | 0.61 | 0.79 | 0.92 | 1.09 | 0.77 ± 0.21 |
| Right kidney | 9 | 0.64 | 0.70 | 1.00 | 1.26 | 1.63 | 1.01 ± 0.34 | 14 | 0.32 | 0.62 | 0.74 | 0.84 | 1.06 | 0.74 ±0.19 |
| Liver | 9 | 5.66 | 7.90 | 10.57 | 13.12 | 16.41 | 10.70 ± 3.37 | 14 | 4.74 | 5.84 | 7.78 | 10.16 | 15.56 | 8.47 ± 3.27 |
| Left lung | 11 | 1.04 | 1.41 | 1.83 | 2.27 | 3.81 | 1.94 ± 0.76 | 14 | 0.95 | 1.15 | 1.37 | 1.65 | 2.91 | 1.50 ± 0.52 |
| Right lung | 11 | 1.31 | 1.35 | 1.85 | 2.60 | 4.10 | 2.15 ± 0.89 | 14 | 0.63 | 1.24 | 1.57 | 2.04 | 3.25 | 1.71 ± 0.65 |
| Pancreas | 3 | 0.31 | 0.31 | 0.40 | 0.46 | 0.46 | 0.39 ± 0.08 | 11 | 0.11 | 0.17 | 0.21 | 0.38 | 0.61 | 0.28 ±0.16 |
| Pituitary | 2 | 0.01 | 0.01 | 0.01 | 0.01 | 0.01 | 0.01 ± 0.00 | 6 | 0.01 | 0.01 | 0.01 | 0.01 | 0.010 | 0.01 ± 0.00 |
| Spleen | 9 | 0.42 | 0.46 | 0.78 | 1.08 | 1.55 | 0.80 ± 0.40 | 14 | 0.15 | 0.38 | 0.59 | 0.89 | 1.26 | 0.60 ± 0.32 |
| Left testis | 6 | 0.05 | 0.06 | 0.18 | 0.35 | 0.38 | 0.20 ±0.14 | |||||||
| Right testis | 6 | 0.03 | 0.08 | 0.21 | 0.37 | 0.46 | 0.23 ±0.17 | |||||||
| Left ovary | 7 | 0.02 | 0.02 | 0.03 | 0.05 | 0.06 | 0.03 ± 0.02 | |||||||
| Right ovary | 7 | 0.01 | 0.02 | 0.04 | 0.04 | 0.05 | 0.03 ± 0.01 | |||||||
| Uterus | 2 | 0.07 | 0.07 | 0.13 | 0.18 | 0.18 | 0.13 ± 0.08 | |||||||
| Prostate | 1 | 0.14 | 0.14 | 0.14 | 0.14 | 0.14 | 0.14 ± 0.00 | |||||||
| Thymus | 11 | 0.39 | 0.64 | 0.85 | 1.36 | 2.45 | 1.02 ± 0.58 | 13 | 0.15 | 0.58 | 0.83 | 0.92 | 1.61 | 0.79 ± 0.35 |
| Left thyroid | 6 | 0.02 | 0.04 | 0.06 | 0.07 | 0.11 | 0.06 ± 0.03 | 11 | 0.03 | 0.03 | 0.04 | 0.06 | 0.13 | 0.05 ± 0.03 |
| Right thyroid | 6 | 0.02 | 0.03 | 0.05 | 0.08 | 0.12 | 0.05 ± 0.04 | 11 | 0.03 | 0.03 | 0.05 | 0.08 | 0.09 | 0.06 ± 0.02 |
Table 5.
Juvenile absolute body weight (kg) and absolute organ weight (g) distribution.
| Body weight or organ weighed | Male | Female | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||||
| N | Min | 25% | 50% | 75% | Max | Mean ± SD | N | Min | 25% | 50% | 75% | Max | Mean ± SD | |
|
| ||||||||||||||
| Body weight | 27 | 0.65 | 1.12 | 1.79 | 2.17 | 3.07 | 1.67 ± 0.65 | 35 | 0.41 | 0.80 | 1.43 | 2.00 | 2.58 | 1.46 ± 0.63 |
| Left adrenal | 27 | 0.10 | 0.18 | 0.20 | 0.24 | 0.33 | 0.21 ± 0.06 | 32 | 0.11 | 0.18 | 0.21 | 0.26 | 0.37 | 0.23 ± 0.06 |
| Right adrenal | 27 | 0.10 | 0.14 | 0.17 | 0.21 | 0.30 | 0.18 ± 0.05 | 33 | 0.11 | 0.14 | 0.18 | 0.21 | 0.35 | 0.18 ± 0.05 |
| Brain | 27 | 59.22 | 62.29 | 65.17 | 70.84 | 80.65 | 66.97 ± 5.82 | 34 | 51.75 | 57.70 | 60.55 | 65.96 | 71.85 | 61.57 ± 5.50 |
| Heart | 23 | 3.28 | 5.13 | 6.85 | 10.01 | 11.89 | 7.35 ± 2.66 | 34 | 2.64 | 4.48 | 6.86 | 9.59 | 12.01 | 7.08 ± 2.82 |
| Left kidney | 23 | 1.44 | 2.61 | 3.59 | 4.63 | 6.29 | 3.66 ± 1.40 | 34 | 1.41 | 2.07 | 4.10 | 5.47 | 11.59 | 4.08 ± 2.11 |
| Right kidney | 23 | 1.42 | 2.54 | 3.91 | 4.77 | 6.41 | 3.71 ± 1.48 | 34 | 1.40 | 2.11 | 3.92 | 5.51 | 11.47 | 4.01 ± 2.09 |
| Liver | 23 | 12.66 | 24.38 | 34.25 | 45.38 | 56.66 | 35.56 ± 12.56 | 34 | 14.19 | 20.73 | 32.02 | 44.03 | 71.65 | 35.31 ± 16.18 |
| Left lung | 23 | 2.65 | 3.34 | 4.06 | 5.04 | 6.74 | 4.24 ± 1.15 | 34 | 1.91 | 3.22 | 4.76 | 5.62 | 7.06 | 4.54 ± 1.49 |
| Right lung | 22 | 3.14 | 4.40 | 4.98 | 6.36 | 8.09 | 5.31 ± 1.37 | 34 | 2.71 | 4.22 | 5.31 | 7.11 | 8.94 | 5.60 ± 1.77 |
| Pancreas | 23 | 0.77 | 1.34 | 2.78 | 4.08 | 4.85 | 2.89 ± 1.42 | 34 | 0.45 | 1.63 | 2.86 | 4.35 | 5.28 | 2.91 ± 1.43 |
| Pituitary | 14 | 0.01 | 0.03 | 0.03 | 0.04 | 0.05 | 0.03 ± 0.01 | 18 | 0.01 | 0.02 | 0.03 | 0.04 | 0.05 | 0.03 ± 0.01 |
| Spleen | 27 | 1.44 | 2.55 | 3.99 | 5.06 | 6.80 | 4.03 ± 1.52 | 34 | 1.17 | 2.37 | 3.80 | 5.51 | 11.10 | 4.15 ± 2.39 |
| Left testis | 22 | 0.07 | 0.15 | 0.25 | 0.37 | 0.48 | 0.26 ± 0.12 | |||||||
| Right testis | 23 | 0.06 | 0.15 | 0.23 | 0.40 | 0.58 | 0.27 ± 0.14 | |||||||
| Left ovary | 31 | 0.02 | 0.04 | 0.07 | 0.11 | 0.23 | 0.08 ± 0.05 | |||||||
| Right ovary | 31 | 0.03 | 0.04 | 007 | 0.11 | 0.17 | 0.08 ± 0.04 | |||||||
| Uterus | 26 | 0.09 | 0.14 | 0.23 | 0.35 | 0.51 | 0.25 ± 0.13 | |||||||
| Prostate | 17 | 0.11 | 0.17 | 0.20 | 0.23 | 0.26 | 0.20 ± 0.04 | |||||||
| Thymus | 23 | 0.30 | 3.18 | 4.08 | 4.80 | 9.09 | 4.10 ± 1.84 | 34 | 0.58 | 1.94 | 2.82 | 3.87 | 9.67 | 3.13 ± 1.73 |
| Left thyroid | 23 | 0.04 | 0.14 | 0.18 | 0.21 | 0.27 | 0.17 ± 0.06 | 32 | 0.05 | 0.12 | 0.15 | 0.22 | 0.37 | 0.17 ± 0.07 |
| Right thyroid | 23 | 0.06 | 0.11 | 0.18 | 0.21 | 0.31 | 0.18 ± 0.07 | 32 | 0.05 | 0.12 | 0.15 | 0.21 | 0.46 | 0.17 ± 0.09 |
Table 6.
Peripubertal absolute body weight (kg) and absolute organ weight (g) distribution.
| Body weight or organ weighed | Male | Female | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||||
| N | Min | 25% | 50% | 75% | Max | Mean ± SD | N | Min | 25% | 50% | 75% | Max | Mean ± SD | |
|
| ||||||||||||||
| Body weight | 18 | 1.69 | 2.19 | 2.84 | 4.39 | 6.10 | 3.30 ± 1.45 | 22 | 1.73 | 2.18 | 2.50 | 3.16 | 4.72 | 2.67 ± 0.69 |
| Left adrenal | 18 | 0.18 | 0.25 | 0.31 | 0.37 | 0.52 | 0.32 ±0.10 | 17 | 0.22 | 0.28 | 0.29 | 0.36 | 0.40 | 0.31 ± 0.06 |
| Right adrenal | 17 | 0.17 | 0.20 | 0.26 | 0.29 | 0.43 | 0.25 ± 0.06 | 17 | 0.19 | 0.24 | 0.27 | 0.30 | 0.44 | 0.28 ± 0.06 |
| Brain | 18 | 56.02 | 61.95 | 70.00 | 73.13 | 77.89 | 67.83 ± 6.96 | 18 | 52.06 | 60.17 | 64.21 | 66.38 | 75.05 | 64.01 ± 5.20 |
| Heart | 18 | 6.44 | 11.18 | 14.11 | 15.90 | 26.50 | 14.05 ± 4.67 | 19 | 8.10 | 10.30 | 11.57 | 13.57 | 19.98 | 12.22 ± 3.06 |
| Left kidney | 18 | 3.90 | 5.45 | 6.50 | 9.08 | 14.39 | 7.28 ± 2.72 | 19 | 4.43 | 5.50 | 6.21 | 6.97 | 9.12 | 6.46 ±1.41 |
| Right kidney | 18 | 3.81 | 5.44 | 6.56 | 9.08 | 14.13 | 7.24 ± 2.59 | 18 | 4.17 | 5.69 | 6.22 | 6.78 | 9.15 | 6.36 ± 1.28 |
| Liver | 17 | 41.54 | 48.52 | 61.64 | 72.21 | 147.89 | 64.76 ± 25.66 | 19 | 36.01 | 46.69 | 53.38 | 88.75 | 110.80 | 63.13 ± 22.57 |
| Left lung | 18 | 4.71 | 5.98 | 6.40 | 12.17 | 17.38 | 8.71 ± 4.11 | 18 | 4.25 | 5.45 | 6.62 | 8.40 | 12.42 | 6.87 ± 2.07 |
| Right lung | 18 | 5.79 | 7.10 | 8.23 | 15.16 | 26.14 | 10.98 ± 5.79 | 18 | 5.34 | 6.27 | 7.82 | 9.53 | 18.58 | 8.70 ± 3.52 |
| Pancreas | 18 | 3.11 | 4.50 | 4.95 | 7.28 | 9.40 | 5.82 ± 1.83 | 19 | 3.66 | 4.49 | 4.86 | 6.43 | 10.67 | 5.64 ± 1.86 |
| Pituitary | 18 | 0.02 | 0.03 | 0.05 | 0.06 | 0.07 | 0.05 ± 0.02 | 17 | 0.03 | 0.04 | 0.05 | 0.05 | 0.09 | 0.05 ± 0.01 |
| Spleen | 17 | 1.39 | 3.74 | 5.01 | 7.63 | 10.10 | 5.60 ± 2.57 | 19 | 2.71 | 4.10 | 5.33 | 8.20 | 13.48 | 6.19 ± 2.60 |
| Left testis | 18 | 0.15 | 0.40 | 0.87 | 8.12 | 18.67 | 4.42 ± 6.36 | |||||||
| Right testis | 17 | 0.21 | 0.43 | 0.85 | 0.60 | 17.07 | 3.71 ± 5.54 | |||||||
| Left ovary | 16 | 0.07 | 0.10 | 0.12 | 0.19 | 0.36 | 0.15 ± 0.08 | |||||||
| Right ovary | 16 | 0.06 | 0.09 | 0.12 | 0.20 | 0.45 | 0.17 ± 0.12 | |||||||
| Uterus | 15 | 0.23 | 0.70 | 0.89 | 5.39 | 6.46 | 2.11 ± 2.36 | |||||||
| Prostate | 17 | 0.17 | 0.24 | 0.32 | 1.20 | 3.84 | 0.96 ± 1.18 | |||||||
| Thymus | 18 | 0.29 | 1.80 | 2.81 | 4.13 | 5.84 | 2.91 ± 1.52 | 18 | 0.54 | 2.14 | 2.75 | 3.66 | 5.52 | 2.92 ± 1.35 |
| Left thyroid | 18 | 0.09 | 0.14 | 0.18 | 0.28 | 0.55 | 0.22 ±0.12 | 18 | 0.10 | 0.13 | 0.18 | 0.25 | 0.30 | 0.19 ± 0.07 |
| Right thyroid | 17 | 0.11 | 0.17 | 0.20 | 0.27 | 0.37 | 0.22 ± 0.08 | 18 | 0.10 | 0.15 | 0.17 | 0.25 | 0.30 | 0.19 ± 0.07 |
Table 7.
Young adult absolute body weight (kg) and absolute organ weight (g) distribution.
| Body weight or organ weighed | Male | Female | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||||
| N | Min | 25% | 50% | 75% | Max | Mean ± SD | N | Min | 25% | 50% | 75% | Max | Mean ± SD | |
|
| ||||||||||||||
| Body weight | 26 | 3.49 | 5.57 | 6.27 | 7.73 | 11.40 | 6.60 ± 1.79 | 38 | 2.07 | 2.78 | 3.06 | 3.66 | 6.18 | 3.34 ± 0.92 |
| Left adrenal | 27 | 0.20 | 0.46 | 0.59 | 0.77 | 1.22 | 0.64 ± 0.27 | 36 | 0.20 | 0.30 | 0.38 | 0.48 | 0.79 | 0.39 ±0.13 |
| Right adrenal | 26 | 0.16 | 0.35 | 0.55 | 0.66 | 1.42 | 0.55 ± 0.26 | 38 | 0.12 | 0.25 | 0.29 | 0.42 | 0.67 | 0.34 ±0.13 |
| Brain | 25 | 55.00 | 66.17 | 71.23 | 76.77 | 92.90 | 71.55 ± 7.65 | 39 | 52.20 | 58.41 | 61.01 | 65.36 | 82.27 | 62.23 ± 6.02 |
| Heart | 24 | 16.21 | 21.09 | 26.90 | 33.58 | 51.00 | 27.67 ± 8.45 | 39 | 9.40 | 13.12 | 15.72 | 19.38 | 32.70 | 16.76 ± 5.06 |
| Left kidney | 25 | 5.58 | 9.69 | 12.01 | 14.95 | 32.79 | 13.58 ± 6.52 | 39 | 5.26 | 6.50 | 7.31 | 8.01 | 11.82 | 7.57 ± 1.52 |
| Right kidney | 26 | 5.41 | 9.55 | 11.96 | 14.20 | 30.53 | 13.80 ± 6.65 | 39 | 4.90 | 6.58 | 7.41 | 8.17 | 11.81 | 7.50 ± 1.56 |
| Liver | 27 | 72.50 | 105.88 | 119.10 | 172.10 | 251.18 | 137.82 ± 50.90 | 40 | 53.81 | 69.05 | 76.42 | 94.72 | 149.31 | 83.06 ± 20.62 |
| Left lung | 26 | 8.44 | 11.89 | 13.81 | 22.75 | 55.64 | 19.04 ± 11.89 | 34 | 5.28 | 6.58 | 7.36 | 8.41 | 13.24 | 7.95 ± 2.11 |
| Right lung | 26 | 7.73 | 14.18 | 16.75 | 24.14 | 63.38 | 21.83 ± 14.01 | 35 | 6.17 | 7.55 | 8.90 | 11.77 | 21.40 | 10.08 ± 3.45 |
| Pancreas | 27 | 4.66 | 6.65 | 9.07 | 11.71 | 18.17 | 9.30 ± 3.06 | 41 | 3.21 | 4.88 | 5.82 | 6.94 | 9.49 | 5.92 ± 1.58 |
| Pituitary | 25 | 0.03 | 0.07 | 0.10 | 0.15 | 0.24 | 0.11 zt 0.06 | 35 | 0.03 | 0.06 | 0.07 | 0.09 | 0.11 | 0.07 ± 0.02 |
| Spleen | 24 | 2.69 | 5.56 | 7.30 | 8.70 | 18.83 | 7.97 ±4.14 | 40 | 2.26 | 4.59 | 5.85 | 9.03 | 15.04 | 6.94 ± 3.28 |
| Left testis | 26 | 9.36 | 15.87 | 22.61 | 26.07 | 32.20 | 20.99 ± 6.91 | |||||||
| Right testis | 26 | 8.94 | 14.98 | 22.51 | 26.38 | 30.69 | 20.57 ± 6.71 | |||||||
| Left ovary | 24 | 0.10 | 0.15 | 0.21 | 0.46 | 0.72 | 0.30 ± 0.21 | |||||||
| Right ovary | 20 | 0.09 | 0.14 | 0.18 | 0.27 | 0.42 | 0.20 ± 0.08 | |||||||
| Uterus (ovxa) | 8 | 0.46 | 0.66 | 0.98 | 1.99 | 5.19 | 1.55 ± 1.57 | |||||||
| Uterus (non-ovxb) | 21 | 0.90 | 3.05 | 4.70 | 6.06 | 14.87 | 5.36 ± 3.49 | |||||||
| Prostate | 10 | 1.55 | 2.37 | 4.33 | 7.49 | 11.36 | 5.15 ± 3.32 | |||||||
| Thymus | 12 | 0.73 | 1.33 | 2.07 | 3.06 | 3.62 | 2.19 ± 0.96 | 32 | 0.56 | 1.29 | 2.61 | 3.58 | 5.05 | 2.56 ± 1.40 |
| Left thyroid | 26 | 0.14 | 0.27 | 0.36 | 0.39 | 0.77 | 0.36 ±0.14 | 39 | 0.11 | 0.19 | 0.24 | 0.33 | 0.74 | 0.27 ±0.12 |
| Right thyroid | 26 | 0.17 | 0.29 | 0.37 | 0.44 | 0.79 | 0.38 ±0.15 | 39 | 0.08 | 0.18 | 0.28 | 0.35 | 0.63 | 0.28 ±0.12 |
Ovariectomized.
Non-ovariectomized.
Table 8.
Adult absolute body weight (kg) and absolute organ weight (g) distribution.
| Body weight or organ weighed | Male | Female | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||||
| N | Min | 25% | 50% | 75% | Max | Mean ± SD | N | Min | 25% | 50% | 75% | Max | Mean ± SD | |
|
| ||||||||||||||
| Body weight | 92 | 3.08 | 5.26 | 5.95 | 6.80 | 11.48 | 6.20 ± 1.63 | 452 | 1.45 | 2.70 | 3.03 | 3.52 | 6.11 | 3.20 ± 0.73 |
| Left adrenal | 93 | 0.24 | 0.35 | 0.42 | 0.55 | 1.03 | 0.46 ±0.16 | 442 | 0.15 | 0.28 | 0.35 | 0.43 | 0.94 | 0.38 ±0.14 |
| Right adrenal | 94 | 0.11 | 0.27 | 0.33 | 0.44 | 0.93 | 0.38 ±0.16 | 448 | 0.09 | 0.22 | 0.27 | 0.34 | 0.71 | 0.30 ±0.12 |
| Brain | 89 | 53.91 | 62.86 | 67.40 | 72.88 | 87.33 | 68.29 ± 6.97 | 454 | 46.20 | 56.84 | 60.00 | 63.81 | 79.29 | 60.40 ± 5.49 |
| Heart | 96 | 14.75 | 26.32 | 32.15 | 38.63 | 57.86 | 32.66 ± 9.04 | 450 | 5.70 | 14.87 | 18.10 | 22.07 | 37.06 | 18.66 ± 5.27 |
| Left kidney | 95 | 7.20 | 9.37 | 10.50 | 12.83 | 22.40 | 11,58± 3.20 | 451 | 4.36 | 6.22 | 7.14 | 8.37 | 14.56 | 7.54 ± 1.92 |
| Right kidney | 94 | 7.40 | 9.09 | 10.57 | 12.82 | 22.80 | 11.50 ± 3.19 | 447 | 4.04 | 6.19 | 7.07 | 8.29 | 14.00 | 7.42 ± 1.82 |
| Liver | 96 | 76.97 | 98.94 | 116.46 | 153.05 | 308.20 | 131.93 ± 48.03 | 444 | 41.06 | 64.07 | 74.91 | 92.71 | 175.45 | 81.02 ± 24.69 |
| Left lung | 94 | 7.70 | 9.90 | 11.48 | 14.29 | 27.46 | 12.45 ± 3.55 | 420 | 4.51 | 6.94 | 8.13 | 10.69 | 22.98 | 9.57 ± 4.01 |
| Right lung | 92 | 9.40 | 11.94 | 13.22 | 16.21 | 28.08 | 14.61 ± 3.95 | 421 | 5.16 | 8.35 | 9.77 | 12.56 | 27.19 | 11.52 ± 4.91 |
| Pancreas | 90 | 3.63 | 7.00 | 8.57 | 10.42 | 16.42 | 8.68 ± 2.33 | 429 | 0.66 | 5.15 | 6.28 | 7.58 | 13.05 | 6.45 ± 1.90 |
| Pituitary | 87 | 0.05 | 0.07 | 0.09 | 0.11 | 0.17 | 0.09 ± 0.03 | 416 | 0.03 | 0.06 | 0.07 | 0.08 | 0.14 | 0.07 ± 0.02 |
| Spleen | 96 | 2.79 | 9.67 | 12.48 | 18.20 | 37.24 | 14.74 ± 7.75 | 432 | 1.35 | 5.19 | 7.23 | 10.05 | 25.18 | 8.21 ± 4.05 |
| Left testis | 87 | 7.08 | 16.83 | 20.81 | 24.43 | 46.50 | 21.18 ± 6.69 | |||||||
| Right testis | 85 | 5.81 | 17.59 | 20.84 | 24.46 | 35.47 | 20.98 ± 5.47 | |||||||
| Left ovary | 175 | 0.05 | 0.17 | 0.24 | 0.31 | 0.84 | 0.26 ±0.12 | |||||||
| Right ovary | 178 | 0.08 | 0.16 | 0.23 | 0.29 | 0.77 | 0.24 ±0.12 | |||||||
| Uterus (ovxa) | 187 | 0.59 | 1.02 | 1.25 | 1.55 | 8.31 | 1.60 ± 1.25 | |||||||
| Uterus (non-ovxb) | 181 | 0.45 | 3.49 | 4.64 | 7.11 | 14.40 | 5.41 ± 2.82 | |||||||
| Prostate | 76 | 1.93 | 4.29 | 5.19 | 6.22 | 11.36 | 5.30 ± 1.66 | |||||||
| Thymus | 68 | 0.06 | 1.41 | 2.33 | 3.19 | 7.89 | 2.46 ± 1.53 | 351 | 0.05 | 1.27 | 2.20 | 3.25 | 8.73 | 2.46 ±1.51 |
| Left thyroid | 94 | 0.14 | 0.31 | 0.43 | 0.56 | 0.91 | 0.45 ±0.17 | 429 | 0.10 | 0.23 | 0.30 | 0.39 | 0.76 | 0.32 ±0.13 |
| Right thyroid | 93 | 0.16 | 0.33 | 0.44 | 0.60 | 1.20 | 0.47 ±0.19 | 429 | 0.08 | 0.23 | 0.31 | 0.41 | 0.79 | 0.33 ±0.14 |
Ovariectomized.
Non-ovariectomized.
Table 9.
Aged absolute body weight (kg) and absolute organ weight (g) distribution.
| Body weight or organ weighed | Male | Female | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||||||
| N | Min | 25% | 50% | 75% | Max | Mean ± SD | N | Min | 25% | 50% | 75% | Max | Mean ± SD | |
|
| ||||||||||||||
| Body weight | 78 | 4.10 | 5.02 | 5.83 | 6.46 | 10.20 | 5.90 ± 1.27 | 179 | 1.86 | 2.80 | 3.31 | 3.86 | 6.36 | 3.45 ± 0.90 |
| Left adrenal | 74 | 0.16 | 0.34 | 0.38 | 0.47 | 0.90 | 0.42 ±0.14 | 171 | 0.17 | 0.29 | 0.34 | 0.43 | 0.88 | 0.38 ±0.13 |
| Right adrenal | 73 | 0.09 | 0.25 | 0.29 | 0.36 | 0.70 | 0.31 ± 0.11 | 169 | 0.12 | 0.22 | 0.26 | 0.34 | 0.73 | 0.29 ± 0.11 |
| Brain | 73 | 50.68 | 62.52 | 66.54 | 70.75 | 85.30 | 66.56 ±6.13 | 172 | 41.20 | 55.68 | 58.82 | 62.64 | 69.73 | 58.82 ± 5.04 |
| Heart | 75 | 15.06 | 23.32 | 30.90 | 34.24 | 57.09 | 29.82 ± 8.09 | 173 | 8.56 | 17.31 | 20.43 | 24.64 | 39.11 | 20.70 ±6.13 |
| Left kidney | 72 | 7.00 | 9.18 | 10.62 | 11.66 | 20.43 | 11.14 ± 3.04 | 173 | 3.37 | 6.44 | 7.42 | 8.64 | 15.15 | 7.70 ± 1.83 |
| Right kidney | 73 | 6.99 | 9.36 | 10.36 | 12.01 | 21.46 | 11.22 ± 3.02 | 171 | 4.54 | 6.43 | 7.36 | 8.45 | 14.47 | 7.63 ± 1.76 |
| Liver | 74 | 16.14 | 92.43 | 104.14 | 127.41 | 237.01 | 114.28 ±38.19 | 171 | 43.07 | 66.37 | 74.94 | 94.37 | 167.82 | 82.00 ± 22.70 |
| Left lung | 71 | 8.29 | 10.56 | 12.11 | 13.79 | 22.20 | 12.82 ± 3.17 | 161 | 3.85 | 7.44 | 8.86 | 11.39 | 24.17 | 10.24 ± 4.33 |
| Right lung | 69 | 8.48 | 12.27 | 13.78 | 16.03 | 28.50 | 14.56 ± 3.62 | 156 | 5.88 | 8.57 | 10.25 | 13.16 | 28.01 | 11.62 ± 4.63 |
| Pancreas | 72 | 1.54 | 6.49 | 7.91 | 9.34 | 14.89 | 7.98 ± 2.39 | 159 | 2.37 | 5.07 | 6.27 | 7.60 | 11.71 | 6.43 ±1.91 |
| Pituitary | 73 | 0.02 | 0.07 | 0.09 | 0.11 | 0.22 | 0.09 ± 0.04 | 158 | 0.03 | 0.06 | 0.08 | 0.09 | 0.17 | 0.08 ± 0.02 |
| Spleen | 74 | 5.09 | 8.47 | 12.40 | 15.72 | 35.38 | 13.25 ± 6.03 | 163 | 2.15 | 6.32 | 7.99 | 11.33 | 26.14 | 9.06 ± 4.21 |
| Left testis | 68 | 7.20 | 16.24 | 19.16 | 23.95 | 32.66 | 19.70 ± 5.46 | |||||||
| Right testis | 68 | 5.57 | 16.09 | 19.55 | 23.82 | 39.41 | 20.29 ±6.13 | |||||||
| Left ovary | 20 | 0.11 | 0.17 | 0.25 | 0.35 | 0.51 | 0.27 ± 0.11 | |||||||
| Right ovary | 20 | 0.09 | 0.16 | 0.24 | 0.28 | 0.45 | 0.24 ±0.10 | |||||||
| Uterus (ovxa) | 102 | 0.71 | 1.03 | 1.19 | 1.53 | 6.45 | 1.46 ± 0.86 | |||||||
| Uterus (non-ovxb) | 30 | 2.19 | 2.77 | 3.71 | 5.39 | 8.68 | 4.33 ± 1.84 | |||||||
| Prostate | 68 | 1.68 | 4.28 | 5.03 | 5.86 | 9.94 | 5.23 ± 1.48 | |||||||
| Thymus | 60 | 0.15 | 0.97 | 1.78 | 2.84 | 7.78 | 2.14 ± 1.61 | 118 | 0.13 | 1.10 | 1.86 | 2.81 | 7.64 | 2.15 ± 1.47 |
| Left thyroid | 76 | 0.13 | 0.32 | 0.46 | 0.59 | 1.15 | 0.48 ± 0.21 | 159 | 0.11 | 0.25 | 0.31 | 0.41 | 0.88 | 0.34 ±0.14 |
| Right thyroid | 75 | 0.17 | 0.37 | 0.50 | 0.58 | 1.03 | 0.48 ±0.17 | 159 | 0.12 | 0.26 | 0.34 | 0.43 | 0.90 | 0.36 ±0.14 |
Ovariectomized.
Non-ovariectomized.
Table 10.
Body and organ weight differences by subspecies; analysis is limited to young adult and adult animals.
| Body weight or organ weighed | Female | Male | |||||||
|---|---|---|---|---|---|---|---|---|---|
|
|
|
||||||||
| Chinese | Indonesian | Malaysian | Mauritian | P value | Chinese | Indonesian | Mauritian | P value | |
|
| |||||||||
| Body weight (kg) | a | b | ab | a | <.003 | a | b | a | <.02 |
| Mean | 3.96 | 3.16 | 3.74 | 4.29 | 7.20 | 5.93 | 8.22 | ||
| SD | 0.96 | 0.70 | 0.32 | 1.13 | 2.01 | 1.35 | 2.17 | ||
| N | 11 | 464 | 5 | 5 | 13 | 91 | 11 | ||
| Brain (g) | a | b | a | ab | <.006 | a | b | a | <.006 |
| Mean | 64.73 | 60.15 | 71.16 | 65.36 | 75.87 | 67.06 | 74.03 | ||
| SD | 4.25 | 5.33 | 5.65 | 6.01 | 7.07 | 6.46 | 5.06 | ||
| N | 15 | 460 | 6 | 7 | 13 | 86 | 11 | ||
| Brain % | a | b | ab | ab | <.0001 | a | a | a | NSD |
| Mean | 1.46 | 1.97 | 1.95 | 1.54 | 1.07 | 1.16 | 0.98 | ||
| SD | 0.54 | 0.42 | 0.12 | 0.54 | 0.36 | 0.29 | 0.37 | ||
| N | 15 | 457 | 5 | 6 | 13 | 85 | 11 | ||
| Left kidney (g) | a | b | a | a | <.009 | a | a | a | NSD |
| Mean | 9.19 | 7.42 | 10.37 | 9.63 | 13.22 | 11.30 | 13.83 | ||
| SD | 2.52 | 1.78 | 2.69 | 2.29 | 4.13 | 3.31 | 5.73 | ||
| N | 12 | 460 | 7 | 7 | 13 | 94 | 9 | ||
| Left kidney % | a | b | a | a | <.02 | a | a | a | NSD |
| Mean | 0.21 | 0.24 | 0.34 | 0.22 | 0.18 | 0.19 | 0.22 | ||
| SD | 0.07 | 0.06 | 0.10 | 0.07 | 0.04 | 0.06 | 0.12 | ||
| N | 12 | 458 | 5 | 6 | 13 | 90 | 11 | ||
| Right kidney (g) | a | b | a | a | <.0025 | a | a | a | NSD |
| Mean | 9.11 | 7.31 | 9.87 | 9.66 | 13.29 | 11.17 | 15.76 | ||
| SD | 2.28 | 1.70 | 2.62 | 2.38 | 3.82 | 3.16 | 7.80 | ||
| N | 12 | 455 | 7 | 7 | 13 | 94 | 9 | ||
| Right kidney % | a | a | b | a | <.02 | a | a | a | NSD |
| Mean | 0.21 | 0.24 | 0.34 | 0.22 | 0.19 | 0.20 | 0.22 | ||
| SD | 0.07 | 0.06 | 0.14 | 0.08 | 0.04 | 0.07 | 0.10 | ||
| N | 12 | 454 | 5 | 6 | 13 | 91 | 11 | ||
| Liver (g) | a | a | a | b | <.0023 | ab | a | b | <.02 |
| Mean | 106.12 | 79.48 | 113.63 | 119.35 | 147.27 | 124.18 | 168.12 | ||
| SD | 21.21 | 23.08 | 33.19 | 35.36 | 49.20 | 41.84 | 57.65 | ||
| N | 12 | 454 | 6 | 7 | 13 | 94 | 11 | ||
| Liver % | a | b | b | b | <.0002 | a | a | a | NSD |
| Mean | 2.43 | 2.58 | 4.76 | 2.72 | 2.03 | 2.16 | 2.07 | ||
| SD | 0.82 | 0.77 | 2.26 | 0.89 | 0.39 | 0.94 | 0.57 | ||
| N | 12 | 452 | 5 | 6 | 13 | 90 | 11 | ||
| Spleen (g) | a | b | ab | ab | <.002 | a | b | ab | <.03 |
| Mean | 4.18 | 8.30 | 7.18 | 6.18 | 6.25 | 14.53 | 12.39 | ||
| SD | 2.38 | 3.99 | 4.43 | 2.14 | 1.68 | 7.16 | 10.32 | ||
| N | 12 | 441 | 7 | 7 | 13 | 93 | 9 | ||
| Spleen % | a | ab | be | c | <.002 | a | b | ab | <.0001 |
| Mean | 0.09 | 0.28 | 0.45 | 0.14 | 0.09 | 0.25 | 0.18 | ||
| SD | 0.04 | 0.15 | 0.54 | 0.05 | 0.03 | 0.12 | 0.12 | ||
| N | 12 | 443 | 5 | 6 | 13 | 90 | 11 | ||
Males of Malaysian origin were too few in number for analysis. Means sharing a letter are not statistically different; P values are included if < .05.
Table 11.
Dietary effects on body weights and organ weights as a percentage of body weight.
| Body weight or organ weighed | Female | Male | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||
| Diet | N | Mean | SD | P | Diet | N | Mean | SD | P | |
|
| ||||||||||
| Body weight (kg) | Chow | 36 | 3.189 | 0.580 | .7837 | Chow | 37 | 6.877 | 2.158 | .0411 |
| Western | 383 | 3.218 | 0.733 | Western | 68 | 6.075 | 1.168 | |||
| Left adrenal % | Chow | 36 | 0.018 | 0.013 | .0195 | Chow | 35 | 0.010 | 0.005 | .0042 |
| Western | 385 | 0.012 | 0.011 | Western | 69 | 0.007 | 0.003 | |||
| Right adrenal % | Chow | 37 | 0.013 | 0.008 | .0035 | Chow | 35 | 0.008 | 0.004 | .0014 |
| Western | 386 | 0.009 | 0.004 | Western | 69 | 0.006 | 0.003 | |||
| Heart % | Chow | 38 | 0.452 | 0.102 | <.0001 | Chow | 34 | 0.429 | 0.120 | <.0001 |
| Western | 377 | 0.614 | 0.144 | Western | 69 | 0.569 | 0.133 | |||
| Left kidney % | Chow | 38 | 0.283 | 0.095 | .0034 | Chow | 36 | 0.226 | 0.093 | .0059 |
| Western | 379 | 0.234 | 0.054 | Western | 69 | 0.179 | 0.042 | |||
| Right kidney % | Chow | 38 | 0.280 | 0.093 | .0031 | Chow | 36 | 0.219 | 0.084 | .0086 |
| Western | 377 | 0.231 | 0.054 | Western | 69 | 0.179 | 0.042 | |||
| Liver % | Chow | 38 | 2.997 | 1.058 | .0111 | Chow | 36 | 2.210 | 0.645 | .0367 |
| Western | 376 | 2.529 | 0.779 | Western | 68 | 1.927 | 0.645 | |||
| Left lung % | Chow | 38 | 0.413 | 0.255 | .0478 | Chow | 36 | 0.299 | 0.170 | .0005 |
| Western | 363 | 0.327 | 0.183 | Western | 68 | 0.188 | 0.045 | |||
| Right lung % | Chow | 38 | 0.477 | 0.291 | .0679 | Chow | 36 | 0.341 | 0.188 | .0007 |
| Western | 362 | 0.386 | 0.203 | Western | 68 | 0.224 | 0.051 | |||
| Pituitary % | Chow | 34 | 0.004 | 0.005 | .775 | Chow | 33 | 0.002 | 0.001 | .0254 |
| Western | 361 | 0.003 | 0.015 | Western | 69 | 0.001 | 0.000 | |||
| Spleen % | Chow | 38 | 0.218 | 0.211 | .1161 | Chow | 36 | 0.132 | 0.078 | <.0001 |
| Western | 365 | 0.275 | 0.152 | Western | 69 | 0.264 | 0.121 | |||
| Thymus % | Chow | 15 | 0.049 | 0.033 | .0012 | Chow | 14 | 0.029 | 0.016 | .0141 |
| Western | 326 | 0.084 | 0.053 | Western | 61 | 0.043 | 0.023 | |||
| Left thyroid % | Chow | 36 | 0.007 | 0.003 | <.0001 | Chow | 35 | 0.006 | 0.002 | <.0001 |
| Western | 360 | 0.010 | 0.004 | Western | 69 | 0.008 | 0.003 | |||
| Right thyroid % | Chow | 37 | 0.007 | 0.003 | <.0001 | Chow | 35 | 0.006 | 0.002 | <.0001 |
| Western | 360 | 0.011 | 0.004 | Western | 69 | 0.009 | 0.003 | |||
Each P value refers to the difference between Chow and Western diet for the organ to the left, for each sex.
Body Weight
Body weight differed by age and sex. Body weight, organized by age group, was significant when comparing all ages (P < .001), but was not significantly different between the three adult categories (young adults, adults, and aged animals) within each sex category. Male/female differences were significant in all three adult groups (P < .0001). Female infants weighed a mean 0.25 kg ± 0.08 kg, and males, 0.32 kg ± 0.12 kg. Body weight in adulthood, typical of animals in regulatory studies, was on average 3.20 kg ± 0.73 kg in females. Adult males had a greater mean body weight of 6.20 kg ± 1.63 kg (P < .0001) compared with females. Males had more variability in body weight throughout the lifespan. The age by sex interaction was significantly different (P < .0001); males tended to increase in body weight from young adulthood to adulthood, whereas females had less weight gain after reaching young adulthood.
Adrenal Glands
The left adrenal gland weight was on average 0.38 g ± 0.14 g in adult females and 0.46 g ± 0.16 g in adult males. Right adrenal gland weight was 0.30 g ± 0.12 g in adult females and 0.38 g ± 0.16 g in adult males. On average, males had greater absolute adrenal gland weights than females. In contrast, as a percentage of body weight, female adrenal weights were significantly higher in all age groups except infants (P < .0001). For both males and females, adrenal gland weight as a percentage of body weight was significantly greater during infancy, declined with maturity post-young adult, and leveled off for the remainder of life. The adrenals were roughly 0.05% of the body weight in infants, and 0.01% of body weight in juvenile and adult groups; infant and juvenile percentages were different from each other and adults (P < .02). There was no significant interaction between age and sex. The left adrenal gland was roughly 10% heavier than the right in adult animals regardless of age or sex (P < .0001).
Brain
The brain was 60.40 g ± 5.49 g in adult females and greater in males at an average of 68.29 g ± 6.97 g. Absolute brain weights for both males and females were level and consistent from juvenile age through adulthood and senescence. As a percentage of body weight, there was significant interaction between age and sex with a P value of .02; female relative brain weights were greater than those of males. The brain as a percentage of body weight was significantly greater during infancy for both males and females (roughly 14% of body weight in females and 12% in males, P < .0001 relative to all other ages) and declined with age, reaching 5% in female juveniles, 4% in male juveniles (P < .0001 for juveniles of either sex vs other ages), 2% in adult females, and 1% in adult males. No decrease in the brain as a percentage of body weight was seen in aged animals.
Heart
The absolute weight of the heart in adult females was 18.66 g ± 5.27 g. In adult males, it was greater at an average 32.66 g ± 9.04 g. As a percentage of body weight, heart weights were generally 0.5% to 0.7% of body weight. Percentage heart weight in females and males was significantly lower in juvenile and all adult animals (P < .0001) relative to infants. There was no significant overall interaction between age and sex for the percentage weight of the heart (P = .06).
The weight of perfusion-fixed hearts was greater by 4 to 6 grams relative to fresh organ weights (data not shown). This effect was significant at P < .0001 for absolute heart weight of adult animals and for percentage heart weight in young adults, adults, and aged animals. No data were available for perfusion-fixed hearts of infants or juveniles.
Kidneys
The right kidney absolute weight was 7.54 g ± 1.92 g in adult females and greater at 11.50 g ± 3.19 g in adult males. Left kidney weight was 7.42 g ± 1.82 g in adult females and greater in adult males at 11.58 g ± 3.20 g, whereas percentage kidney weights were higher in females (P < .0001). Both males and females had significantly larger relative percentage kidney weights in the infant and juvenile groups compared with all other age groups (P < .0001). For both males and females, kidneys as a percentage of body weight declined with maturity. Relative kidney weight was roughly 0.25% to 0.3% of body weight in infant and juvenile animals and declined to roughly 0.2% of body weight in adult groups. Left-right differences were not significant.
Liver
Liver absolute weight was 81.02 g ± 24.69 g in adult females. It was greater in adult males at 131.93 g ± 48.03 g (P < .0001). Males had heavier livers throughout maturity, but female livers were greater in terms of body weight percentage (P = .0067). Both male and female livers were significantly greater as a percentage of body weight during infancy (3%−3.5%) and then declined and leveled to around 2% to 2.5% with maturity. There was no significant difference between age and sex effects on the liver as a percentage of body weight.
Lungs
The absolute weight for the left lung was 9.57 g ± 4.01 g in adult females and 12.45 g ± 3.55 g in adult males. Right lung weight including the accessory lobe was on average 11.52 g ± 4.91 g for adult females and 14.61 g ± 3.95 g for adult males. Males had greater lung weights than females overall by absolute weight, but percentage of body weight did not differ by sex. For both males and females, total lung weight as a percentage of body weight declined with maturity from roughly 1.4% in infants to 0.7% in adults. The right lung was 8% to 21% heavier than the left for all groups except infants (P < .0001 for all ages and both sexes except for young adults where P was <.04).
Pancreas
Pancreas absolute weight was 6.45 g ± 1.90 g in adult females and 8.68 g ± 2.33 g in adult males. Young adult males had heavier pancreata in terms of absolute weight (P < .0001). The pancreas was roughly 0.15% to 0.2% of body weight in adult animals. Pancreas weight as a percentage of body weight was significantly lower in infant females in comparison with adults (0.1% of body weight for infants and 0.15%2% for adults, P < .0001), and differed by sex (female > male) in young adults and adults (P < .0001). A decline in relative pancreatic weight with maturity was more apparent in females.
Pituitary
Pituitary weight was 0.07 g ± 0.02 g in adult females and 0.09 g ± 0.03 g in adult males. There was significant difference by age, such that the pituitary was a greater percentage of body weight for females than males during infancy (P < .0001), but this was based on a low number of observations (n = 2 females and 6 males). In adults, pituitary weight was roughly 0.002% of body weight.
Spleen
Spleen was generally 0.2% to 0.25% of body weight, irrespective of age. The spleen on average weighed 8.21 g ± 4.05 g in adult females and more in adult males at an average of 14.74 g ± 7.75 g. In young adult males, spleen weight was lowest in terms of percentage of body weight, differing significantly from juveniles and adults (P = .002); there were no other significant relationships between percentage spleen weight, age, and sex.
Testes
Adult males had an average left testis weight of 21.18 g ± 6.69 g and a right testis weight of 20.98 g ± 5.47 g. The left-right difference was not statistically significant. Testes as a percentage of body weight increased from juvenile age throughout maturity (P = .0001), and the percentage of body weight of both testes significantly increased during adulthood. In sexually mature animals, testis weight was >0.25% of body weight. Testicular weight did not decline in aged animals as a percentage of body weight.
Ovaries
On average, left adult ovaries weighed 0.26 g ± 0.12 g and right adult ovaries weighed 0.24 g ± 0.12 g. Ovaries as a percentage of body weight significantly increased from the juvenile to adult life stage (P < 001). From young adulthood onward, both ovary weights as a percentage of body weight plateaued.
Uterus
Among ovary-intact females, uterine weights were significantly lower in juvenile animals at 0.25 g ± 0.13 g relative to 5.41 g ± 2.82 g in adults (P < .0218). Uterine absolute weights and percentage of body weights were further organized into subjects that were ovariectomized in young adulthood and those that were not ovariectomized (intact). As adults, the average uterine weight for ovariectomized subjects was 1.60 g ± 1.25 g, in comparison with the average adult non-ovariectomized uterine weight of 5.41 g ± 2.82 g. As a percentage of body weight for young adults, uterine weights were approximately 0.2% to 0.3% of body weight, compared with 0.05% of body weight in ovariectomized subjects (P < .0001).
Prostate
Average absolute weight of the adult prostate was 5.30 g ± 1.66 g, or roughly 0.08% of body weight. Prostate weights as a percentage of body weight was significantly lower in juvenile and peripubertal animals when compared with young adults, adults, and aged animals (P < .0001). Prostate weights did not increase further in aged animals relative to adults.
Thymus
Thymic absolute weight on average was 2.46 g ± 1.51 g in adult females and 2.46 g ± 1.53 g in adult males. The thymus was roughly 0.3% of body weight in infants, 0.2% in juveniles, and 0.05% or less in adults; this drop in thymic weight with maturity was highly significant (P < .0001). There was a significant interaction of age and sex, such that female infants and juveniles had significantly different percentages of body weights; the thymus occupied a greater percentage of body weight for female infants, a greater percentage for male juveniles, and a slightly greater percentage for all adult female groups (P < .0002 for the age by sex interaction).
Thyroid
Absolute weight of the left lobe of the thyroid was 0.32 g ± 0.13 g in adult females and 0.45 g ± 0.17 g in adult males. The right lobe of the thyroid was 0.33 g ± 0.14 g for adult females and 0.47 g ± 0.19 g in adult males. Males had greater absolute thyroid weights than females, but females had greater thyroid weights than males as a percentage of body weight for all adult groups (P < .05). For both males and females, each thyroid as a percentage of body weight was significantly greater during infancy (P < .0001). In infants, thyroid weight was roughly 0.015% to 0.025% of body weight, declining to 0.005% to 0.010% of body weight in adults.
Subspecies Effects
Effects of geographic/genetic origin are shown in Table 10. These represent young adult and adult animals, with males and females considered separately. With respect to body weight, Indonesian animals were smaller than animals of Chinese or Mauritian origin. Organ weight differences are included if they were consistently significant for both absolute and relative percentage body weight. Spleen weight was greatest for Indonesian animals. Liver weight was greatest for Mauritian animals. Brain weight and kidney weight were lowest for Indonesian animals.
Dietary Effect
Within the subset of 634 animals for which long-term dietary interventions were assessed (Table 3), there were significant effects on total body weight and organ weights. Males fed a high-fat “Western” diet (animal protein sources, >30% of calories from fat, and low fiber) had significantly lower body weight (P < .04), and significantly higher percentages of body weight for the heart, spleen, thymus, and thyroids, and lower percentage weights for adrenals, kidneys, liver, lungs, and pituitary. Body weights and percentage weights of the lungs and pituitary did not differ in females; the pattern of weight differences by diet was similar in females for other organs. These findings are summarized in Table 11.
Table 3.
Diet compositions.
| Diet | Chow | Western |
|---|---|---|
|
| ||
| N female | 44 | 390 |
| N male | 40 | 71 |
| Gross energy (Kcal/g) | 3.07–3.19 | 3.81–4.77 |
| Protein (% of calories) | 18%–31 % | 18%–20% |
| Protein source | Soy, grains | Milk |
| Fat (% of calories) | 11%–l 3% | 29%–45% |
| Carbohydrates (% of calories) | 58%–69% | 35%–51% |
| Crude fiber (% of calories) | 4.5%–5.2% | 5.5%–10.5% |
Discussion
These data were gathered in order to provide a reference for normal absolute organ weights and for organ weights as a percentage of body weight for M fascicularis as there are no current published references for this species. This information is pertinent due to the increased usage of cynomolgus macaques in medical research, especially in studies for drug development and toxicology. Primary findings demonstrated that male cynomolgus monkeys had overall greater body weights and absolute organ weights than their female counterparts; however, females had greater organ weights as a percentage of body weight for most organs studied. Larson’s study of M arctoides14 also showed that females have greater organ weights as a proportion of their body weight in comparison with males. Sex differences were evident starting around 5 to 7 years of age. In Andrade’s study,31 sexual maturity in cynomolgus monkeys was shown at around 32 months of age, corresponding to roughly the ages at which sex differences emerged in our data.
In terms of absolute organ weights, the weights of lungs, pituitary, kidneys, testes, prostate, uterus, adrenal glands, thyroid, pancreas, and spleen leveled off after the monkeys reached sexual maturity. The heart weight slightly increased with age among adult animals. In contrast, adult absolute brain and thymus weights slightly declined with age. Organ weights as a percentage relative to body weight that leveled off after young adulthood was reached included kidneys, lungs, thymus, brain, and liver. The testes were the only organ to increase as a percentage of body weight with maturity. The left testis on average weighed more than the right testis, but this difference was not significant. This is in contrast to human adult males in which the left is often 10% lower in weight.32 As a percentage of body weight, uteri of non-ovariectomized or intact subjects were greater than those of ovariectomized subjects. Organ weights with no distinct pattern in relation to body weight included heart, spleen, and pancreas. From infancy through young adulthood, adrenal, brain, kidney, lung, liver, thymus, and thyroid weight, as a percentage of body weight, declined. The relative weight of the brain in particular was remarkably high in infancy, relative to adulthood. This is similarly shown in Cupp and Uemura’s study13 of rhesus macaques.
This study was accomplished retrospectively with cynomolgus macaques of both sexes and all ages, with a majority falling into adulthood. Because this study was meant to represent normalcy, extreme statistical outliers were excluded.
Analysis of differences in body and organ weights between animals of different geographic/genetic origin revealed subspecies differences in spleen, liver, brain, and kidney weights; however, numbers were limited for some subspecies. In a prior report, subspecies differences in organ weights were found to be unremarkable, with the exception of Vietnamese monkeys having lower spleen weights than those of Mauritius or Philippine origin.33
Diets of two different macronutrient compositions were examined in a subset of animals and those consuming a carbohydrate-rich, low-fat, high-fiber diet that was low in animal protein had significantly higher total body weight and significantly lower relative weights of heart, thymus, spleen, and thyroid; in males, the relative weight of the brain was lower. This finding is in agreement with studies of dietary macronutrient composition in humans, corresponding to the “Atkins diet” effect.34
This study can be used as a foundation and reference for further studies with cynomolgus monkeys as research subjects.
Acknowledgments
This study was made possible by the NIH institutional training grant T35 OD010946. The authors are grateful to past and present staff of the Comparative Pathology Laboratory at the Clarkson Research Campus, and the faculty and staff of the Section on Comparative Medicine at the Wake Forest School of Medicine. The authors express special thanks for the data management assistance of Ms Tasha Lanier.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by an institutional training grant (NIH T35 OD010946).
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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