Review on testicular development, structure, function, and regulation in common marmoset

Abstract

The common marmoset (Callithrix jacchus) is a New World primate that has been used increasingly in toxicological evaluations including testing for testicular toxicity of pharmaceutical and environmental chemicals. Information on structural and functional characteristics of the testis in common marmosets ("marmoset" in this review) is critical for designing experiments, interpreting data collected, and determining relevance to humans in risk assessment. This study provides a comprehensive review on testicular development, structure, function, and regulation in common marmosets. There is little information regarding testicular formation and development during gestation. Based on the overall pattern of embryonic development in marmosets, it is postulated that gonadal formation and testicular differentiation most likely takes place during gestational Week 6-12. After birth, the neonatal period of the first 2-3 weeks and the pubertal period from Months 6-12 are critical for establishment of spermatogenesis in the adult. In the adult, a nine-stage model has been used to describe the organization of seminiferous epithelium and multiple stages per tubular cross-section have been observed. Seminiferous epithelium is organized in a wave or partial-wave manner. There are on average two stages per cross-section of seminiferous tubules in adult marmoset testis. Sertoli cells in the marmoset have a uniform morphology. Marmoset spermatogenesis has a high efficiency. The prime determinant of germ cell production is proliferation and survival of spermatogonia. Sertoli cell proliferation during the neonatal period is regulated by follicle-stimulating hormone (FSH), but chorionic gonadotropin (CG), instead of luteinizing hormone (LH), is the only gonadotropin with luteinizing function in marmoset. The receptor gene for CG in marmoset is unique in that it does not have exon 10. Marmosets have a "generalized steroid hormone resistance," i.e., relatively high levels of steroid hormones in circulation and relatively low response to exogenous steroids. Blockage of FSH, CG, and testosterone production during the first 3 months after birth does not cause permanent damage to the male reproductive system. Initiation of spermatogenesis in the marmoset requires unique factors that are probably not present in other mammals. Normal male marmosets respond to estradiol injection positively (increased LH or CG levels), a pattern seen in normal females or castrated males, but not usually in normal males of other mammalian species. It seems that the endocrine system including the testis in marmosets has some unique features that have not been observed in rodents, Old World primates, and humans, but detailed comparison in these features among these species will be presented in another review. Based on the data available, marmoset seems to be an interesting model for comparative studies. However, interpretation of experimental findings on the testicular effects in marmosets should be made with serious caution. Depending on potential mode of testicular actions of the chemical under investigation, marmoset may have very limited value in predicting potential testicular or steroid hormone-related endocrine effects of test chemicals in humans.