Study Question: What is the genetic landscape within the testis of the juvenile rhesus monkey (Macaca mulatta) that underlies the decision of undifferentiated spermatogonia to commit to a pathway of differentiation when puberty is induced prematurely by exogenous LH and FSH stimulation?
Summary Answer: Forty-eight hours of gonadotrophin stimulation of the juvenile monkey testis resulted in the appearance of differentiating B spermatogonia and the emergence of 1362 up-regulated and 225 down-regulated testicular mRNAs encoding a complex network of proteins ranging from enzymes regulating Leydig cell steroidogenesis to membrane receptors, and from juxtacrine and paracrine factors to transcriptional factors governing spermatogonial stem cell fate.
What Is Known Already: Our understanding of the cell and molecular biology underlying the fate of undifferentiated spermatogonia is based largely on studies of rodents, particularly of mice, but in the case of primates very little is known. The present study represents the first attempt to comprehensively address this question in a highly evolved primate.
Objective: To determine the molecular characteristics of human spermatogonia and optimize methods to enrich spermatogonial stem cells (SSCs).
Design: Laboratory study using human tissues.
Setting: Research institute.
As the spermatogenesis- and oogenesis-specific basic helix-loop-helix 1 (SOHLH1) transcription factor has been shown to be essential for spermatogonial differentiation in mice, we examined the immunoexpression of this protein in the testis of the rhesus monkey (Macaca mulatta) during puberty, the stage of development when spermatogonial differentiation is initiated in higher primates. Immunopositive SOHLH1 cells were observed only on the basement membrane of the seminiferous cords and tubules. Prior to puberty, essentially 100% of SOHLH1-positive spermatogonia co-expressed the glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRα1), a marker for undifferentiated spermatogonia, and >80% of the immunopositive SOHLH1 cells exhibited only cytoplasmic staining of this transcription factor.
View Article and Find Full Text PDFThe foundation for development of the male reproduction system occurs in utero, but relatively little is known about the regulation of primate fetal testis maturation. Our laboratories have shown that estrogen regulates key aspects of the physiology of pregnancy and fetal development. Therefore, in the present study, we characterized and quantified germ cells and Sertoli cells in the fetal baboon testis in late normal gestation (i.
View Article and Find Full Text PDFAcute effects of CDB-4022 on testicular ultrastructure were determined. Rats were treated orally with vehicle or a maximally effective single dose of CDB-4022 or Di-n-pentylphthalate (DPP). Preserved testes were processed for transmission electron microscopy.
View Article and Find Full Text PDFThe present study was undertaken to examine the antispermatogenic effect of l-CDB-4022 in the adult male cynomolgus monkey. Monkeys (four per group) were dosed via nasogastric tube for 7 d with l-CDB-4022 at 12.5 mg/kg.
View Article and Find Full Text PDFThis review examines the neurobiology, endocrinology, and cell biology underlying the development of the testis from birth until puberty in the rhesus monkey, a representative higher primate.
View Article and Find Full Text PDFThe purpose of the present study was to determine whether dark and pale type A spermatogonia (Ad and Ap, respectively) are mitotically active during prepubertal development and whether proliferation of these germ cells during this protracted phase of primate development occurs predominantly during infancy before gonadotropin secretion is arrested. Four neonate (1-2 days of age), four infant (4-5 mo of age), and four juvenile (14-17 mo of age) rhesus monkeys (Macaca mulatta) were castrated 2 h after receiving an i.v.
View Article and Find Full Text PDFThe goal of the present study was to examine the relative roles of testosterone (T) and FSH in the proliferation and differentiation of pale type A (Ap) spermatogonia in the rhesus monkey (Macaca mulatta). Twenty adult male monkeys were treated with daily injections of a GnRH-receptor antagonist, acyline, to suppress endogenous gonadotropin secretion during an experiment comprising three phases. Phase 1 established a chronic hypogonadotropic state marked by a profound decrease in testicular size.
View Article and Find Full Text PDFThis study examined, in adult monkeys, the role that gonadotropin-independent mechanisms play in compensation of testosterone (T) secretion by the testis that remains after unilateral orchidectomy (UO). We employed a model (testicular clamp), in which endogenous gonadotropin secretion was abolished with a GnRH receptor antagonist, and the gonadotropin drive to the testes was concomitantly replaced with an invariant iv pulsatile infusion of recombinant human LH and FSH (1-min pulse every 2.5 h: LH, 0.
View Article and Find Full Text PDFAlthough a marked pubertal increase in Sertoli cell number is a hallmark of testicular development in the rhesus monkey, the ontogeny of this somatic cell type before puberty is less clear. To clarify this issue, groups (n = 4) of neonate (1-2 d old), infant (4-5 months old), juvenile (14-17 months old), and adult male rhesus monkeys were injected with 5-bromo-2'-deoxyuridine (BrdU) 2 h before castration. Tissue was fixed in Bouin's fluid, and the percentage of BrdU-labeled Sertoli cells at each developmental stage was calculated.
View Article and Find Full Text PDFThis study examined the relative role of FSH and LH in governing testicular inhibin B secretion in the rhesus monkey. Adult male monkeys, rendered hypogonadotropic and hypogonadal by administration of a GnRH receptor antagonist (acyline), were implanted with testosterone (T)-filled or empty capsules. Following T-induced restoration of spermatogenesis, both groups received recombinant human FSH and vehicle for 12 d.
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