PARENT SESSION

(24) EXOGENOUS GONADOTROPIN SUPPORTS ACCELERATED MATURATION OF INFANT PRIMATE TESTIS TISSUE XENOGRAFTS IN MICE.

Rathi, Rahul¹, Zeng, Wenxian¹, Honaramooz, Ali ¹, Meyers, Stuart², Dobrinski, Ina¹, ¹ University of Pennsylvania, Kennett Square, PA² University of California, Davis, CA

ABSTRACT- The study of testicular maturation and onset of spermatogenesis in primates is challenging due to the long time required to attain puberty (12-14 yr in humans; 32-44 mo in macaques). Recently, we reported accelerated maturation of testis tissue from sexually immature (13 mo old) rhesus monkeys (Macaca mulatta) after ectopic xenografting into castrated, immunodeficient mice, supported by endogenous gonadotropins provided by the mouse host. In the present study we investigated whether accelerated maturation of testis tissue xenografts from younger primates (3, 6, and 8 mo old) could be induced by endogenous mouse gonadotropins alone or by further stimulation with hCG. Testicular tissue from rhesus monkeys (3 mo and 6 mo), and cynomolgus monkeys (Macaca fasciculata; 3 mo and 8 mo) was grafted under the back skin of castrated immunodeficient mice (n ≥ 4 per donor). Recipient mice (n=26) were treated from 1 mo (rhesus), 3 mo (rhesus), or 7 mo (cynomolgus) post grafting (10 I.U. hCG 2 or 3 times per week for 12 or 24 weeks) with 34 untreated recipients serving as controls. Grafts were examined histologically for germ cell proliferation and differentiation. After treatment for 12 or 24 weeks, grafts from 3 mo old donors showed tubular expansion with germ cells at the basal lamina of the seminiferous tubules while grafts from untreated mice did not show any maturational changes. Xenografts from 6 mo old rhesus monkeys recovered after 12 weeks of treatment contained pachytene spermatocytes. Elongated spermatids were present in grafts of the 6 mo old rhesus monkey after 24 weeks of treatment and of the 8 mo old cynomolgus monkey after 12 weeks of treatment. Grafts recovered at the same time points from untreated mice only showed tubular expansion with germ cells at the basal lamina. A significant difference in the seminal vesicle weights, an indicator for production testosterone from grafts, was observed between treated and untreated mice (>200mg vs <20mg). These results indicate that stimulation with hCG was required to accelerate testicular maturation in tissue from infant primates, and that response to gonadotropic stimulation was age dependent. Xenografting therefore provides an accessible system for the study and manipulation of testicular development and spermatogenesis in primates. Supported by 1 R01 RR17359-01

KEY WORDS: Primate, Spermatogenesis, Testis, Xenografts