Talk:Monkey Development

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Cite this page: Hill, M.A. (2021, January 16) Embryology Monkey Development. Retrieved from


Ma H, Zhai J, Wan H, Jiang X, Wang X, Wang L, Xiang Y, He X, Zhao ZA, Zhao B, Zheng P, Li L & Wang H. (2019). In vitro culture of cynomolgus monkey embryos beyond early gastrulation. Science , 366, . PMID: 31672918 DOI.

In vitro culture of cynomolgus monkey embryos beyond early gastrulation.

Abstract Gastrulation is a key event in embryonic development when the germ layers are specified and the basic animal body plan is established. The complexities of primate gastrulation remain a mystery because of the difficulties in accessing primate embryos at this stage. Here, we report the establishment of an in vitro culture (IVC) system that supports the continuous development of cynomolgus monkey blastocysts beyond early gastrulation up to 20 days after fertilization. The IVC embryos highly recapitulated the key events of in vivo early postimplantation development, including segregation of the epiblast and hypoblast, formation of the amniotic and yolk sac cavities, appearance of the primordial germ cells, and establishment of the anterior-posterior axis. Single-cell RNA-sequencing analyses of the IVC embryos provide information about lineage specification during primate early postimplantation development. This system provides a platform with which to explore the characteristics and mechanisms of early postimplantation embryogenesis in primates with possible conservation of cell movements and lineages in human embryogenesis. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Comment in Primate embryos grown in the lab for longer than ever before. [Nature. 2019] PMID: 31672918 DOI: 10.1126/science.aax7890


Nuclear-mitochondrial incompatibility in interorder rhesus monkey-cow embryos derived from somatic cell nuclear transfer

Primates. 2016 May 10. [Epub ahead of print]

Kwon D1, Koo OJ2, Kim MJ1, Jang G1,3, Lee BC4,5.


Monkey interorder somatic cell nuclear transfer (iSCNT) using enucleated cow oocytes yielded poor blastocysts development and contradictory results among research groups. Determining the reason for this low blastocyst development is a prerequisite for optimizing iSCNT in rhesus monkeys. The aim of this study was to elucidate nuclear-mitochondrial incompatibility of rhesus monkey-cow iSCNT embryos and its relationship to low blastocyst development. Cytochrome b is a protein of complex III of the electron transport chain (ETC). According to meta-analysis of amino acid sequences, the homology of cytochrome b is 75 % between rhesus monkeys and cattle. To maintain the function of ETC after iSCNT, 4n iSCNT embryos were produced by fusion of non-enucleated cow oocytes and rhesus monkey somatic cells. The blastocyst development rate of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Formation of reactive oxygen species (ROS) is an indirect indicator of ETC activity of cells. The ROS levels of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Collectively, rhesus monkey iSCNT embryos reconstructed with cow oocytes have nuclear-mitochondrial incompatibility due to fundamental species differences between rhesus monkeys and cattle. Nuclear-mitochondrial incompatibility seems to correlate with low ETC activity and extremely low blastocyst development of rhesus monkey-cow iSCNT embryos. KEYWORDS: Blastocysts; Cow; Electron transport chain; Interorder somatic cell nuclear transfer; Rhesus monkey

PMID 27165688


Generation of pancreatic insulin-producing cells from rhesus monkey induced pluripotent stem cells

Diabetologia. 2011 Jul 14. [Epub ahead of print]

Zhu FF, Zhang PB, Zhang DH, Sui X, Yin M, Xiang TT, Shi Y, Ding MX, Deng H. Source Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, Shenzhen, People's Republic of China.


AIMS/HYPOTHESIS: The generation of induced pluripotent stem cells (iPSCs) provides a promising possibility for type 1 diabetes therapy. However, the generation of insulin-producing cells from iPSCs and evaluation of their efficacy and safety should be achieved in large animals before clinically applying iPSC-derived cells in humans. Here we try to generate insulin-producing cells from rhesus monkey (RM) iPSCs.

METHODS: Based on the knowledge of embryonic pancreatic development, we developed a four-stage protocol to generate insulin-producing cells from RM iPSCs. We established a quantitative method using flow cytometry to analyse the differentiation efficiency. In addition, to evaluate the differentiation competence and function of RM iPSC-derived cells, transplantation of stage 3 and 4 cells into immunodeficient mice was performed.

RESULTS: RM iPSCs were sequentially induced to definitive endoderm (DE), pancreatic progenitors (PP), endocrine precursors (EP) and insulin-producing cells. PDX1(+) PP cells were obtained efficiently from RM iPSCs (over 85% efficiency). The TGF-β inhibitor SB431542 promoted the generation of NGN3(+) EP cells, which can generate insulin-producing cells in vivo upon transplantation. Finally, after this four-stage differentiation in vitro, insulin-producing cells that could secrete insulin in response to glucose stimulation were obtained. When transplanted into mouse models for diabetes, these insulin-producing cells could decrease blood glucose levels in approximately 50% of the mice.

CONCLUSIONS/INTERPRETATION: We demonstrate for the first time that RM iPSCs can be differentiated into functional insulin-producing cells, which will provide the basis for investigating the efficacy and safety of autologous iPSC-derived insulin-producing cells in a rhesus monkey model for type 1 diabetes therapy.

PMID 21755313


Pregnancy initiation in the rhesus macaque: towards functional manipulation of the maternal-fetal interface

Reprod Biol Endocrinol. 2004 Jun 16;2:35.

Golos TG.

National Primate Research Center and Department of Obstetrics and Gynecology, University of Wisconsin Medical School, University of Wisconsin-Madison, Madison, WI 53715-1299, USA. Abstract Nonhuman primates provide an important opportunity to define the mechanisms that contribute to the success of early pregnancy. We have focused for several years now on defining the expression of novel placental major histocompatibility complex (MHC) class I molecules. In parallel, we have used reagents against human immune cell markers to characterize the leukocyte population in the decidua and have demonstrated dynamic changes in these cell populations during the first 5 weeks of gestation. The challenge is to identify the possible role(s) of placental MHC class I in modifying/directing the maternal endometrial or systemic immune system in the post-implantation period. Foremost among the challenges is the difficulty in modifying placental function. In the instance of trophoblast surface proteins, passive immunization studies are feasible, although limitations include the empirical nature of this approach, as well as the inability to modify intracellular function. We have shown that using lentiviral vectors to effect preimplantation gene transfer for transgene expression in the placenta is not only feasible, but of good efficiency. In addition to transgene overexpression, robust approaches for knocking down/knocking out placental gene expression are essential. Recent developments in RNA interference approaches may allow "transient knockout" experiments. While the rhesus monkey has been our model of choice, currently there are limitations in the number of available female rhesus monkeys of reproductive age for research in early pregnancy. It is critical that the technologies for advanced study move forward in other species. The baboon has been used significantly in reproductive tract biology and early pregnancy research and important models have been developed for manipulation of the maternal-fetal interface. Additional characterization of other species, such as the cynomolgus and African green (vervet) monkey is critical. Given the limitations on antigen recognition when using human reagents, we also propose that the development of panels of primate-specific anti-leukocyte antibodies is essential for moving forward nonhuman primate reproductive research.

PMID 15200676

Uterine receptivity and implantation: the regulation and action of insulin-like growth factor binding protein-1 (IGFBP-1), HOXA10 and forkhead transcription factor-1 (FOXO-1) in the baboon endometrium

Reprod Biol Endocrinol. 2004 Jun 16;2:34.

Kim JJ, Fazleabas AT.

Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA. Abstract In primates, the phase of the menstrual cycle when the uterus becomes receptive is initially dependent on estrogen and progesterone. Further morphological and biochemical changes are induced as a result of biochemical signals between the embryo and the maternal endometrium. Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation and is similar to that described for the rhesus macaque. In the baboon, when chorionic gonadotropin is infused in a manner that mimics blastocyst transit, this has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial plaques are evident. The glandular epithelium responds by inducing transcriptional and post-translational modifications in the major secretory product, glycodelin. The stromal fibroblasts initiate their differentiation process into a decidual phenotype and are characterized by the expression of actin filaments. Decidualization, is the major change that occurs in the primate endometrium after conception. During this process the fibroblast-like stromal cells change morphologically into polygonal cells and express specific decidual proteins. Studies in the baboon demonstrated that insulin-like growth factor binding protein-1 (IGFBP-1) gene expression is a conceptus-mediated response. Subsequent studies in vitro established that IGFBP-1 is transcriptionally regulated by FOXO1 and HOXA10 which together upregulate the IGFBP-1 promoter activity. A baboon endometriosis model was utilized to determine if the changes observed during uterine receptivity in normally cycling animals were compromised. The data suggests that in animals with disease, markers of uterine receptivity are not appropriately expressed in the eutopic endometrium. It is possible that these differences influence the fertility of the animals with disease and the baboon could be used as a primate model to study the causes of infertility as a result of endometriosis.

PMID 15200677


Development of pituitary-adrenal endocrine function in the marmoset monkey: infant hypercortisolism is the norm

J Clin Endocrinol Metab. 2002 Feb;87(2):691-9.

Pryce CR, Palme R, Feldon J. Source Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, CH-8603 Schwerzenbach, Switzerland.


Early life stress, involving activation of the hypothalamic-pituitary-adrenal (HPA) system, is associated with altered functioning of stress-related systems in adulthood. In the rat, postnatal development is characterized by low basal HPA activity and stress hyporesponsiveness, and infant exposure to atypical glucocorticoid levels leads to chronic alteration of HPA function and HPA-dependent peripheral and central processes. There have been few studies of primate HPA ontogeny, and here we report a study of changes in pituitary-adrenal function between birth and adulthood in the common marmoset monkey. In this simian primate, basal plasma ACTH and cortisol levels were actually elevated in neonates (ACTH, 141 +/- 28 pg/ml; cortisol, 1903 +/- 326 microg/dl) and wk 4 infants (ACTH, 114 +/- 9 pg/ml; cortisol, 290 +/- 8 microg/dl) relative to month 2 infants, juveniles (month 6), subadults (month 12), and adults (>2 yr; ACTH, 37 +/- 4 to 61 +/- 8 pg/ml; cortisol, 101 +/- 2 to 195 +/- 4 microg/dl). In contrast to older life stages, neonates lacked circadian change in their plasma cortisol levels, and this state of consistently high cortisol was associated with large adrenal glands in addition to high ACTH levels. Cerebrospinal fluid cortisol levels were, in accord with plasma levels, higher in wk 4 infants than in juveniles and subadults. In terms of stress response, month 2 infants demonstrated ACTH and cortisol peak stress responses similar to those at older life stages (infant stress cortisol, 185 +/- 36% of basal; subadult stress cortisol, 174 +/- 6% of basal); whereas infant ACTH recovery was also similar to that in older subjects, their cortisol poststress recovery was retarded. This primate, it is proposed, provides an excellent complementary model in which to test hypotheses derived from the rat model relating to HPA system ontogeny and the chronic effects and biomedical implications of hypercorticoidism during early life.

PMID 11836307


Implantation in the baboon: endometrial responses

Semin Reprod Endocrinol. 1999;17(3):257-65.

Fazleabas AT, Kim JJ, Srinivasan S, Donnelly KM, Brudney A, Jaffe RC.

Department of Obstetrics and Gynecology, University of Illinois, Chicago 60612-7313, USA. Abstract Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation. Changes that occur within this window of receptivity and immediately following implantation can be divided into three distinct phases. The first phase, regulated by estrogen and progesterone, is characterized primarily by changes in both the luminal and glandular epithelial cells in preparation for blastocyst apposition and attachment. The second phase is the further modulation of these steroid induced changes in both epithelial and stromal cells by embryonic signals. The final phase is associated with trophoblast invasion and the remodeling of the endometrial stromal compartment. During the initial phase, the actions of estrogen and progesterone are dependent on the presence of specific receptors. Estrogen up-regulates both its own receptor (ER) and the progesterone receptor (PR), while progesterone down-regulates this expression pattern. However, the pattern of progesterone-induced down-regulation of ER and PR is confined to the epithelial cells and demonstrates a gradient effect from the functionalis to the basalis. What is most intriguing is that the loss of epithelial PR is closely correlated with the establishment of uterine receptivity. Coincident with the changes in ER and PR expression, epithelial cells undergo alterations in their cytoskeletal architecture and secretory profile. These changes can be counteracted by PR antagonist treatment during the luteal phase. Although estrogen and progesterone play a critical role in establishing the initial phase of uterine receptivity, it is becoming increasingly evident that the embryo induces functional receptivity in ruminants and rodents. In our studies in the primate, we demonstrate that chorionic gonadotrophin when infused in a manner that mimics blastocyst transit, has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial plaques are evident. The glandular epithelium responds by inducing transcriptional and post-translational modifications in the major secretory product, glycodelin. The stromal fibroblasts initiate their differentiation process into a decidual phenotype and are characterized by the expression of actin filaments. In phase three, blastocyst attachment to the surface epithelium and subsequent implantation is associated with local remodeling of the maternal stroma, smooth muscle, and endothelium of the blood vessels by the trophoblast. In addition, there is a gradual diminution of the epithelial plaques on the luminal surface although the glandular epithelium remains highly secretory. The most dramatic effect is on the stromal fibroblasts, which in response to embryonic stimuli, differentiate into decidual cells, the major cell type of the gestational endometrium. This differentiation is characterized by the expression of insulin-like growth factor binding protein-1 (IGFBP-1) in these cells. The cytokine IL-1 beta is one possible embryonic signal. COX-2 is the rate-limiting enzyme for prostaglandin biosynthesis and transcription of this enzyme in response to the embryonic stimulus (IL-1 beta) results in an increase in prostaglandin biosynthesis in stromal fibroblasts at the site of implantation. Prostaglandins and PGE2 in particular, binds to its specific receptor (EP2 or EP4) and activates adenyl cyclase. The resulting increase in intracellular levels of cAMP can now activate IGFBP-1 gene transcription at the site of implantation. In summary, our studies have demonstrated that chorionic gonadotrophin, when infused into non-pregnant baboons during the window of uterine receptivity can induce epithelial responses that are similar to those observed in a fertile cycle. Stromal differentiation is initiated; however, decidualization requires a signal from the conceptus.

PMID 10797944


Postnatal development of monoamine content and synthesis in the cerebral cortex of rhesus monkeys

Brain Res. 1982 Jul;256(3):339-49.

Goldman-Rakic PS, Brown RM.

Abstract The concentration and rates of synthesis of norepinephrine, dopamine and serotonin were determined by spectrophotofluorometric methods in various cytoarchitectonic areas of the cerebral cortex in 54 rhesus monkeys ranging in age from 1 day to 36 months. For most regions studied, norepinephrine levels exhibit steady increases from birth through 36 months while over the same period changes in dopamine concentration are more complex and variable, particularly in the frontal lobe. Among the 3 monoamines examined, endogenous serotonin content shows the least dramatic and most rapid development, reaching adult values between 2 and 5 months of age in most cortical regions. As a consequence of these developmental shifts, the relationship of monoamine levels in various cortical areas also changes with age. At maturity, however, norepinephrine concentration exceeds that of dopamine and serotonin in the cortex of the frontal and parietal lobes whereas serotonin levels are higher than norepinephrine in the occipital cortex. Changes in rates of synthesis of the catecholamines and serotonin generally parallel developmental changes in concentrations. The greatest increments in catecholamine synthesis occur in prefrontal and posterior association cortices. Smaller but significant increases in serotonin metabolism were measured in the parietal and visual cortex between birth and 36 months while in other areas of the cortex, age-related changes in serotonin synthesis were negligible. A consistent finding at all ages is that the distribution of catecholaminergic synthesis varies inversely with that of serotonergic synthesis, indicating substantial interaction in the regulation of the two cortical systems. The present findings demonstrate that in the rhesus monkey development of monoaminergic storage capacity and synthetic processes: (1) continues over a period of months and years; (2) is generally more rapid for serotonin than for catecholamines; and (3) varies greatly in different cytoarchitectonic regions of the cerebral cortex.

PMID 7104766

Species Information

Rhesus macaque (Macaca mulatta)

Cawthon Lang KA. 2005 July 20. Primate Factsheets: Rhesus macaque (Macaca mulatta) Behavior . <>. Accessed 2012 September 22.

"Females reach puberty around age three while males are sexually mature by age four (Rawlins & Kessler 1986b). The ovarian cycle lasts for 28 days and is characterized by the darkening of the skin surrounding the anogenital region accompanied by menstruation (Catchpole & van Wagenen 1975). Estrus lasts for eight to 12 days, with the day of ovulation occurring at the midpoint of the estrus period. Females have increased sexual activity during ovulation, exhibiting the highest number of copulations seen during the ovarian cycle (Fooden 2000). Females reproduce from three until about 20 years of age (Rawlins & Kessler 1986b). Males reach puberty between three and 3.5 years of age but do not reach adult body size until about eight years old (Dixson & Nevison 1997; Bercovitch et al. 2003). Though males are capable of reproducing by age four, they are not reproductively successful until after age eight, or when they reach adult size. During this time between becoming sexually mature and when they begin to mate, young rhesus macaques are learning the social skills, including fighting ability, that will influence their success throughout their lives (Bercovitch et al. 2003). Both males and females reach sexual maturity sooner in captivity (Catchpole & van Wagenen 1975).

There is marked birth seasonality in rhesus macaques, with the majority of mating occurring in October through December and births coinciding with the end of the rainy season, or during the period of highest food abundance (Lindburg 1971; Qu et al. 1993). At Cayo Santiago, the mating season is much longer and begins in July and lasts until December (Chapais 1986). High-ranking males have more opportunities to mate with females than low-ranking males, but do not always sire a disproportionate number of infants. Lower-ranking males may have similar reproductive success compared to high-ranking males because they are new immigrants and are more attractive to females because of this (Berard 1999). From one breeding season to the next, females will drastically reduce the amount of mating they do with familiar males and over a period of three years, they try not to mate with any familiar males given the opportunity to mate with unfamiliar males (Bercovitch 1997; Berard 1999).

During the breeding season, females enter into consortships with one or more males. An individual female will spend longer amounts of time in contact with, grooming, and mating with these males. Males and female rhesus macaques are promiscuous breeders, mating multiple times with multiple mates (Lindburg 1971). Both males and females initiate these consort relationships and competition for access to mates is related to the high levels of aggression seen in rhesus macaque groups during this time of year. Gestation lasts 164 days in rhesus macaques and the interbirth interval is between 12 and 24 months (Fooden 2000). If a female does not have a successful pregnancy or her infant dies in the first year of life, she is more likely to give birth the following season than a female who successfully rears an infant (Seth 2000)."

Spider Monkey (Ateles geoffroyi)

Males sexually mature at the age of 5, while females are mature at 4 years old. They have no regular breeding season (they breed all year round). Gestation lasts for 226 to 232 days and one baby is born at a time with births occurring in 2 to 4 year intervals. The babies are born black colored and do not acquire the adult coloration until they are in the sub-adult stage (after nursing has finished).

The infant is continuously carried by the mother hanging to the mother’s ventrum until five months of age. After they tend to be transported in the mother’s back, but continue to be nursed by their mother until they are two years old, which is when the sub-adult period starts. Female sub-adults tend to stay with the mother, while male sub-adults do not form prolonged associations with their mothers.