title: Endocrine modulation of the recipient environment affects development of bovine testis tissue ectopically grafted in mice.
abstract: Testis tissue xenografting is a powerful approach for the study of testis development and spermatogenesis, and for fertility preservation in immature individuals. In bovine testis xenografts, maturation and spermatogenesis are inefficient when compared to other species. To evaluate if exogenous modulation of the endocrine milieu in recipient mice will affect spermatogenic efficiency in xenografts from newborn calves, recipient mice were treated with the GnRH antagonist acyline (5 mg/kg s.c. every 2 weeks) to reduce testosterone production in xenografts, or with 6-N-propyl-2-thiouracil (PTU, 0.1% in drinking water for 4 weeks), to induce transient hypothyroidism in recipient mice respectively. Both treatments altered developmental parameters of testis xenografts and reduced germ cell differentiation. While the effects of acyline treatment can be attributed to inhibition of GnRH and gonadotropin action, lower Sertoli cell numbers and decreased seminiferous tubule length observed after PTU treatment were opposite to effects reported previously in rats. Regardless of treatment, Sertoli cells underwent only partial maturation in xenografts as Müllerian inhibiting substance and androgen receptor expression were lower than in donor and adult tissue controls respectively. In conclusion, although treatments did not result in improvement of maturation of bovine testis xenografts, the current study demonstrates that exogenous modulation of the endocrine milieu to affect xenograft development in recipient mice provides an accessible model to study endocrine control of spermatogenesis in large donor species.
authors.affiliation: Center for Animal Transgenesis and Germ Cell Research, New Bolton Center, University of Pennsylvania, Kennett Square, Pennsylvania 19348, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodriguez-Sosa
authors.forename: Guilherme M J
authors.initials: GM
authors.lastname: Costa
authors.forename: Rahul
authors.initials: R
authors.lastname: Rathi
authors.forename: Luiz R
authors.initials: LR
authors.lastname: França
authors.forename: Ina
authors.initials: I
authors.lastname: Dobrinski
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000008:administration & dosage; D002417:Cattle; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D007037:Hypothyroidism / Q000139:chemically induced; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage; D011441:Propylthiouracil / Q000008:administration & dosage; D012708:Sertoli Cells / Q000502:physiology; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology*; D013737:Testis / Q000254:growth & development* / Q000637:transplantation*; D013739:Testosterone / Q000096:biosynthesis / Q000502:physiology*; D013963:Thyroid Hormones / Q000502:physiology*; D014183:Transplantation, Heterologous
chemical_list: D013956:Antithyroid Agents; D009842:Oligopeptides; D013963:Thyroid Hormones; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011441:Propylthiouracil; C109238:acyline