title: Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm.
abstract: Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man's life and may have application for treating some cases of male infertility, including those caused by chemotherapy before puberty. We performed autologous and allogeneic SSC transplantations into the testes of 18 adult and 5 prepubertal recipient macaques that were rendered infertile with alkylating chemotherapy. After autologous transplant, the donor genotype from lentivirus-marked SSCs was evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients after they reached maturity. Allogeneic transplant led to donor-recipient chimerism in sperm from 2/6 adult recipients. Ejaculated sperm from one recipient transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via intracytoplasmic sperm injection. Eighty-one oocytes were fertilized, producing embryos ranging from four-cell to blastocyst with donor paternal origin confirmed in 7/81 embryos. This demonstration of functional donor spermatogenesis following SSC transplantation in primates is an important milestone for informed clinical translation.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Hermann
authors.forename: Meena
authors.initials: M
authors.lastname: Sukhwani
authors.forename: Felicity
authors.initials: F
authors.lastname: Winkler
authors.forename: Julia N
authors.initials: JN
authors.lastname: Pascarella
authors.forename: Karen A
authors.initials: KA
authors.lastname: Peters
authors.forename: Yi
authors.initials: Y
authors.lastname: Sheng
authors.forename: Hanna
authors.initials: H
authors.lastname: Valli
authors.forename: Mario
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Gina
authors.initials: G
authors.lastname: Dargo
authors.forename: Kim
authors.initials: K
authors.lastname: Peterson
authors.forename: Keith
authors.initials: K
authors.lastname: Masterson
authors.forename: Cathy
authors.initials: C
authors.lastname: Ramsey
authors.forename: Thea
authors.initials: T
authors.lastname: Ward
authors.forename: Maura
authors.initials: M
authors.lastname: Lienesch
authors.forename: Angie
authors.initials: A
authors.lastname: Volk
authors.forename: David K
authors.initials: DK
authors.lastname: Cooper
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Kiss
authors.forename: Maria Cecilia T
authors.initials: MC
authors.lastname: Penedo
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Schatten
authors.forename: Shoukhrat
authors.initials: S
authors.lastname: Mitalipov
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Orwig
mesh_terms: D000818:Animals; D008253:Macaca mulatta; D008297:Male; D013091:Spermatogenesis; D013093:Spermatogonia / Q000637:transplantation*; D013094:Spermatozoa / Q000502:physiology*; D033581:Stem Cell Transplantation; D013737:Testis / Q000166:cytology / Q000637:transplantation*