Ovarian senescence in the rhesus monkey (Macaca mulatta)

BACKGROUND: A decline in fertility is evident in human females past their middle thirties. This 'reproductive senescence', marked by a sharp decline in pregnancy rates, may be attributed to reductions in numbers of available oocytes and their quality. Because Old World primates exhibit ovarian morphology and physiological control and timing of menstrual cycles closely resembling those of humans, the current study investigated the rhesus macaque as a potential model for human reproductive senescence. METHODS: Ovaries collected from females aged 1-25 years and divided into five age groups were analysed histologically. RESULTS: General ovarian morphology demonstrated significant changes as the females approached menopause. The proportions of primordial and primary follicles all demonstrated significant differences across age groups (primordial: 77.1, 79.9, 69.7, 62.9, 55.1%; primary: 21.5, 18.8, 28.5, 35.2, 43.1% for age groups 1 to 5 respectively; P<0.0001 for both). Samples from females approaching or undergoing the menopausal transition (aged 20-25 years) demonstrated evidence of ovarian senescence, having scattered and atretic follicles, low numbers of primordial follicles and reduced stromal tissue. CONCLUSION: This study supports the value of the rhesus monkey as a model for reproductive ageing because its ovary undergoes follicular reservoir depletion similar to that seen in humans.     

Carbohydrate cytochemistry of rhesus monkey tracheal epithelium

Three types of nonciliated secretory epithelial cells contribute material to the mucous lining of pulmonary airways: mucous cells, serous cells, and Clara cells. Extensive interspecies variation exists, especially between humans and laboratory mammals, with regard to occurrence, distribution, and granule content of these secretory cells. This study was designed to characterize one aspect of these differences in one species of nonhuman primate, the rhesus monkey. The complex carbohydrates of secretory granules present in the tracheal epithelium were characterized cytochemically. The tracheas of seven monkeys were fixed by airway infusion, processed, and embedded for both light and transmission electron microscopy. Histochemical stains including Alcian blue-periodic acid Schiff, dialyzed iron, and high iron diamine-Alcian blue were applied to serial methacrylate sections. The mucous cells were the predominant secretory cell type of the trachea and contained periodate-reactive sulfated glycoconjugates. The mucous secretory granules, as resolved with the electron microscope, consisted of a mesh or matrix surrounding a biphasic core. The matrix was stained by all cytochemical reactions used, which included periodic acid-thiocarbohydrazide-silver proteinate, dialyzed iron, low iron diamine, and high iron diamine. The biphasic core also reacted with the four stains, but most intensely with high iron diamine. We conclude from this study that 1) the mucous secretory granule contains carbohydrate throughout all phases of the granule, 2) the mucous granule contains periodate-reactive sulfated glycoconjugates, with sulfate esters concentrated in the core of the granule, and 3) the mucous granules of rhesus trachea morphologically and cytochemically resemble those described in human airways.     

Cerebellar regulation of phonation in rhesus monkey (Macaca mulatta)

Summary Five rhesus monkeys (Macaca mulatta) were trained to emit a coo vocalization with a duration of at least 500 msec. After stable performance was achieved cerebellar lesions were introduced, and various pre- and postlesion measures of phonation and of laryngeal EMG activity were compared to assess the effects of the lesions. The phonatory changes were interpreted with respect to possible laryngeal or respiratory modifications. The relation between fundamental frequency and intensity of phonation was changed in some animals, with no obvious alterations in either fundamental frequency or intensity considered separately. Intensity of phonation was decreased while duration was prolonged in two animals. Fundamental frequency of phonation was also affected in some animals. Reliable laryngeal EMG was obtained in two animals and was affected by cerebellar lesions. These results indicate that normal cerebellar function is involved in the control of fundamental frequency, intensity, duration, and the coordination of the laryngeal and respiratory systems for the control of phonation.     

Structural characteristics of the corpus luteum during implantation in the rhesus monkey (Macaca mulatta)

Corpora lutea were obtained from ten pregnant rhesus monkeys during implantation, and the ultrastructure of granulosa and theca lutein cells was characterized. Specimens were individually staged with regard to the extent of implantation and the relationship to the rise in circulating progesterone and estrogen which is characteristic of early pregnancy. Structural changes characteristic of granulosa lutein cells occurring during implantation included: change in form of endoplasmic reticulum from predominantly agranular tubules to predominantly granular cisternae; reduction in size and number of lipid droplets; increase in area occupied by the Golgi and increase in length of the cisternae of the Golgi complex; development of numerous microvillus-lined intracellular spaces; increase in numbers of membrane-bound dense bodies including peroxi-somelike bodies, multivesicular bodies within lobopodia, and other lysosomelike bodies; and alterations of mitochondrial cristae. These changes were suggestive of the production of a secretory protein, rapid utilization of existing steroid precursor reserves for the production of progesterone, and a reduction in capability for steroid precursor accumulation and processing by granulosa lutein cells. Structural changes characteristic of theca lutein cells occurring during implantation included an increase in size and number of lipid droplets, an increase in agranular endoplasmic reticulum, and an increase in area occupied by the Golgi complex. These changes were suggestive of an increased capability for steroid precursor accumulation and processing, perhaps for estrogen production, by the theca lutein cells.     

Age differences in recognition memory of the rhesus monkey (Macaca mulatta)

Aging is accompanied by a gradual decline in memory in both humans and nonhuman primates. To determine whether the impairment in nonhuman primates extends to recognition memory, which is a sensitive index of the integrity of the limbic system, we trained rhesus monkeys of four different age groups (3-6, 14-17, 20-24, and 25-29 years of age) on a delayed nonmatching-to-sample task with trial-unique objects. After the animals had learned the task, which required recognition of single objects presented ten seconds earlier, memory demands were increased by gradually lengthening delay intervals (to 120 seconds) and list lengths (to ten objects). With increasing age, only marginal impairments in learning the basic task were observed. However, clear age-related differences did emerge when either delays or list lengths were increased, with the oldest group of monkeys demonstrating the greatest impairments. The decline in visual recognition ability in aging monkeys parallels the decline in memory observed with advancing age in humans.     

Structure of taste buds in foliate papillae of the rhesus monkey,Macaca mulatta

Taste buds in foliate papillae of the rhesus monkey were examined by electron microscopy. Three distinct cell types were identified. Type I cells were narrow elongated cells containing an oval nucleus, bundles of intermediate filaments, several Golgi bodies, and characteristic apical membrane-bounded dense granules. These cells exhibited morphological variations: some had a moderately dense cytoplasm, perinuclear free ribosomes, and flattened sacs of rough endoplasmic reticulum; others had a more lucent cytoplasm, dilated irregular rough endoplasmic reticulum, lysosome-like dense bodies, and lipid droplets. Type II cells typically contained a spherical, pale nucleus, a prominent nucleolus, supranuclear and infranuclear Golgi bodies, mitochondria with tubular cristae, and one or two centrioles. This cell type, too, showed some variation in the relative amounts of ribosomes and smooth endoplasmic reticulum, which varied inversely with each other. Type III cells were characterized by a clear apical cytoplasm essentially devoid of ribosomes and containing microtubules. In a few type III cells, the peri- and infranuclear regions contained many ribosomes and some rough endoplasmic reticulum. In most Type III cells, there were large numbers of dense and clear vesicles in the peri- and infranuclear regions; some of the vesicles were grouped in synapse-like arrangements with adjacent nerves. The morphological variations exhibited by all three cell types could be accounted for by age differences in each of the cells. This would be consistent with the notion that cell renewal occurs in each of the three cell populations.     

Venous distribution of superficial cervical region in rhesus (Macaca mulatta) monkey

The superficial veins of the cervical region in over 50 Macaca mulatta monkeys were studied. We found, in addition to the external jugular vein, another major vein, which we have termed jugular accessory. It is comparable in size and runs ventral to the external jugular vein. It commenced at the angle of the mouth, ran in a groove on the dorsal aspect of the submandibular gland, and descended on the surface of the sternocleidomastoid muscle where it was connected to the external jugular vein by a short transverse twig. It then descended toward the clavicle, crossed it ventrally, and immediately joined the cephalic vein. The resultant common vein pierced the thoracic wall between the clavicle and first rib and joined the external jugular and axillary veins, producing the subclavian vein. It was the jugular accessory and the external jugular, being connected as described, that formed an "H"-shaped system.     

Proteoglycans and collagen in the intervertebral disc of the rhesus monkey (Macaca mulatta).

The different varieties of supportive tissues in the intervertebral discs of the rhesus monkeys (Macaca mulatta) were investigated with regard to morphology of the collagen fibrils and distribution and localization of proteoglycans (PG). The annulus fibrosus and the nucleus pulposus of the intervertebral disc were structurally closely integrated into the cartilaginous endplates of the vertebral bodies. The collagen fibrils in the intervertebral disc fell into two categories; i.e. thick (70-110 nm) and thin (40-50 nm) ones. In the outer zone of the annulus fibrosus only thick fibrils occurred, while in the regions of the inner part of the annulus fibrosus, in the periphery of the nucleus pulposus and in the cartilaginous endplates both types of fibrils were found. PG were found free in the matrix and in great numbers in association with collagen fibrils in all regions of the intervertebral disc. They interconnected neighbouring fibrils and decorated the surface of the collagen fibrils in irregular orientation. Only the thick fibrils of the annulus fibrosus contained small regularly arranged intrafibrillar PG precipitates. The free precipitates were usually longer and thicker than the collagen-associated PG, in addition they could be branched. Since rhesus monkeys are closely related to humans, they can serve as model organisms and the findings presented may be of relevance to the understanding of the human intervertebral discs.     

Head orientation and handedness trajectory in rhesus monkey infants (Macaca mulatta)

In human and chimpanzee infants, neonatal rightward supine head orientation bias predicts later right hand use preference. In an evolutionarily older primate species such as the rhesus monkey, a left hand preference has been reported, but there are no data on head orientation biases. Supine head orientation bias was measured experimentally in 16 rhesus monkey neonates and compared with prone head orientation bias as well as with various measures of hand use preference. A group-level leftward supine head bias was found that corresponded to greater activity in the left hand while supine; however, supine head orientation did not predict later hand preference as measured by reaching or manipulation on a coordinated bimanual task. These data suggest that a trajectory for handedness in rhesus monkeys may be different from that of humans and chimpanzees.     

Histological changes in the articular eminence and mandibular fossa during growth of the rhesus monkey (Macaca mulatta)

Unlike the mandibular condyle, the temporal component of the temporomandibular joint (TMJ) has been the object of relatively few investigations concerning its growth and remodeling. This report provides qualitative and quantitative documentation of microanatomical changes in the mandibular fossa and articular eminence during growth of the rhesus monkey (Macaca mulatta). The thickness of the fibrous articular tissue and the presence of cartilage cells in its deeper layers were examined histologically in 43 rhesus monkeys at five maturational levels (neonate, infant, juvenile, adolescent, and young adult). Absolute thickness of the articular tissue increased with maturational level in all areas studied, with the increase somewhat more pronounced on the posterior slope and crest of the articular eminence than in the roof of the mandibular fossa. Relative to condylar size, an increase in articularlayer thickness characterized the first three maturational levels, and was followed by a decrease during adolescent and young-adult stages. Articular tissue in the fossa roof constituted a steadily decreasing fraction of the total articular-tissue thickness with age, while relative thickness of the tissue on the posterior slope and crest of the eminence increased with age. These results parallel those obtained for the mandibular condyle, and they are best interpreted to indicate that forces delivered to the joint become directed more anteriorly with age. The overall pattern of topographical variation in articular-tissue thickness and cartilage-cell distribution suggests that greater loading of the lateral aspect of the TMJ, postulated in the human TMJ by various workers, may not be as pronounced in the monkey.     

Impairment of executive function induced by hypertension in the rhesus monkey (Macaca mulatta)

The effects of chronic, untreated hypertension on executive function were investigated in a nonhuman primate model of hypertensive cerebrovascular disease. Executive function was assessed with the Conceptual Set-Shifting Task (CSST). a task adapted from the human Wisconsin Card Sorting Test (WCST). Like the WCST, the CSST requires abstraction of a stimulus set, followed by a series of set shifts. Performance on the CSST by 7 young adult monkeys (Macaca mulatta) with surgically induced hypertension was compared with that of 6 normotensive monkeys. The hypertensive group was significantly impaired relative to the normotensive group in abstraction and set shifting. Although the neural basis of this impairment is unclear, evidence from studies with humans and monkeys suggests that the prefrontal cortex may be the locus for this effect of hypertension.     

The development of auditory event related potentials in the rhesus monkey (Macaca mulatta)

Auditory event related potentials were recorded from neonatal, 3‐month, and 3‐year old rhesus monkeys. Auditory brainstem evoked responses (ABRs) were reliably recorded at all ages. ABR latencies decreased with age. Age effects were greater the more centrally generated the wave. Wave I amplitude decreased with age, Wave II increased, and Wave IV remained about the same. Stimulus rate effects were greater in neonates than older monkeys. Stimulus frequency also affected the ABR, but not differentially as a function of age. Recording montage had a significant effect on the recorded waveform. Wave I tended to be larger in amplitude in horizontal recordings and front–back recordings, while the later waves were relatively more prominent in more vertical montages. Middle latency evoked responses and late potentials were less reliably recorded than the ABR. Their reproducibility improved with age. Auditory event related potentials are promising measures of auditory function for research requiring nonhuman primate models of the developing human. © 1999 John Wiley & Sons, Inc. Dev Psychobiol 34: 37–56, 1999     

Permeability characteristics and osmotic sensitivity of rhesus monkey (Macaca mulatta) oocytes

BACKGROUND: Permeability characteristics and sensitivity to osmotic shock are principal parameters that are important to derive procedures for the successful cryopreservation of mammalian oocytes. METHODS AND RESULTS: The osmotically inactive volume of rhesus monkey oocytes was determined by measuring their volumes in the presence of hypertonic solutions of sucrose from 0.2 to 1.5 mol/l, compared with their volume in isotonic TALP-HEPES solution. Boyle-van't Hoff plots at infinite osmolality indicated that the non-osmotic volumes of immature and mature oocytes were 20 and 17% respectively. Osmotic responses of oocytes exposed to 1.0 mol/l solutions of glycerol, dimethylsulphoxide (DMSO) and ethylene glycol (EG) were determined. Rhesus monkey oocytes appeared to be less permeable to glycerol than to DMSO or to EG. Sensitivity of oocytes to osmotic shock was determined by exposing them to various solutions of EG (0.1 to 5.0 mol/l) and then abruptly diluting them into isotonic medium. Morphological survival, as measured by membrane integrity, of oocytes diluted out of EG depended significantly on the concentration of EG (P < 0.01). CONCLUSION: Determination of permeability characteristics and sensitivity to osmotic shock of rhesus oocytes will aid in the derivation of procedures for their cryopreservation.     

The fine structure of the placental villi of the rhesus monkey(Macaca mulatta)

Placental villi were obtained from monkeys at the Wisconsin Primate Research Center during 50–150 days gestation. As in the human, the villi consist of a vascular mesenchymal core surrounded by inner cytotrophoblastic and outer syncytiotrophoblastic layers. The syncytiotrophoblast contains abundant rough endoplasmic reticulum and a well developed Golgi complex consisting of stacked lamellae and diffuse vesicles. An asymmetrical distribution of ribosomes occurs on RER cisternae associated with mitochondria. Branched microvilli frequently bear dilated tips and resemble stereocilia. Cytoplasmic tufts and microvilli increase the surface area, and the base of the tuft usually contains a large membrane-bound vacuole with a flocculent inclusion of low electron density. These vacuoles are lacking after 100 days. In later stages the syncytiotrophoblast bears irregular microvillous processes and specialized attachment sites at its contact with the basal lamina. Hofbauer cells in the villus core contain numerous large vacuoles, coated pinocytotic vesicles and smooth vesicles apparently derived from ER; the latter are sometimes fused to the large vacuoles. Hofbauer cells appear to be derived from undifferentiated mesenchymal cells.     

Tracheal submucosal gland development in the rhesus monkey, Macaca mulatta: ultrastructure and histochemistry

Summary The submucosal glands are thought to be the primary source of the mucus overlying the primate trachea and conducting airways. This study characterizes the development of submucosal glands in the trachea of the rhesus monkey. Tracheas from 46 age-dated fetal, 8 postnatal and 3 adult rhesus were fixed in glutaraldehyde/paraformaldehyde and slices processed for electron microscopy. The earliest (70 days gestational age (DGA)) indication of gland development was the projection of a group of closely packed electron lucent cells with few organelles and small pockets of glycogen into the submucosa. This configuration was observed up to 110 DGA. In fetuses younger than 87 DGA it was present almost exclusively over cartilaginous areas. Between 80 and 140 DGA, a cylinder of electron lucent cells projected into the submucosal connective tissue perpendicular to the surface. In fetuses younger than 100 DGA, it was restricted to cartilaginous areas. By 90 DGA, some glycogen containing cells in proximal regions contained apical cored granules. By 106 DGA, cells in proximal areas contained apical electron lucent granules. More distal cells had abundant GER and electron dense granules. The most distal cells resembled the undifferentiated cells at younger ages. Ciliated cells were present in the most proximal portions of glands at 120 DGA. This glandular organization was found in older animals, including adults, with the following changes: (1) abundance of proximal cells with electron lucent granules increased; (2) abundance of distal cells with electron dense granules increased; and (3) abundance of distal cells with abundant glycogen and few organelles decreased. We conclude that submucosal gland development in the rhesus monkey: (1) is primarily a prenatal process; (2) occurs first over cartilage; (3) continues into the postnatal period; and (4) involves secretory cell maturation in a proximal to distal sequence with mucous cells differentiating before serous cells.