A shorter interval between irradiation of recipient testis and germ cell transplantation is detrimental to recovery of fertility in rams

Abstract

The objective of the current study was to identify an optimal time period for donor cell transplantation after irradiation in sheep. The testes of recipient rams were treated with a single dose of 15 Gray (Gy) irradiation followed by germ cell transplantation either 3 or 6 weeks later. Transplantation of donor cells at 6 weeks after irradiation resulted in production of donor sperm by all five recipient rams compared with 4 of 11 rams transplanted at 3 weeks. Rams transplanted 3 weeks post-irradiation appeared to show reduced libido and fertility. Two rams produced sperm with low motility (< 20%) and two other rams were azoospermic. More than 1 year after cell transfer, there were heavy infiltrates of CD45-positive cells and more fibrous tissue in 9 of 14 recipient testes (seven rams) that received cells 3 weeks after irradiation. Taken together, these results suggest that the interval between irradiation of recipients and germ cell transplantation affects the success rate of the procedure, with a 6-week interval preferable. The elevated inflammatory/immune reaction may be responsible, at least in part, for the reduced fertility and low libido observed in the rams that received cells 3 weeks post-irradiation.

Isolation, genetic manipulation, and transplantation of canine spermatogonial stem cells: progress toward transgenesis through the male germ-line

“…From this comparison, we conclude that the level of donor engraftment in these two studies was similar, in spite of differences in preconditioning of the recipient tissue or isolation and manipulation of the donor cells. Similar studies with other large animals have yielded variable levels of donor sperm production (Honaramooz et al 2003, Izadyar et al 2003, Herrid et al 2009, Herrid et al 2011, Jahnukainen et al 2011, Hermann et al 2012, Zeng et al 2012, Zeng et al 2013), ranging from less than 1% to as high as 30% in sheep (Herrid et al 2009). …”

“…The development of SSC transplantation in rodents, as an alternative to embryo-mediated gene transfer, opened a new opportunity to explore this relatively less invasive, more efficient and lower cost approach in canines and other larger animal models. Successful SSC transplantations in several large animals (Izadyar et al 2003, Kim et al 2008, Herrid et al 2011, Jahnukainen et al 2011, Hermann et al 2012, Zeng et al 2012), led us believe this approach could be applied to the dog model.…”

“…However, most of the recovery was undoubtedly from endogenous SSC that escaped the preconditioning, possibly inhibiting donor engraftment. The typical interval of several weeks between irradiation and transplant is based on the logic that tissue damage and inflammation caused by irradiation will interfere with homing of stem cells to their niche (Herrid et al 2011). However, there is not a compelling body of empirical data to confirm this.…”

“…SSC transplantation, and subsequent donor sperm production has now been reported in pigs, sheep, bulls, goats, monkeys and dogs (Izadyar et al 2003, Kim et al 2008, Herrid et al 2011, Jahnukainen et al 2011, Hermann et al 2012, Zeng et al 2012, Zeng et al 2013). More importantly, SSC transplants in both sheep (Herrid et al 2009) and goats (Honaramooz et al 2003) have led to the birth of donor-derived offspring through normal mating.…”

Depletion of testis cell populations in pre-pubertal Bos indicus cattle by irradiation

“…Testicular cells are known to be able to recover from irradiation damage; goat testis treated with fractionated irradiation (2 Gy × 3 days) exhibited recovery of spermatogenesis in 60% of tubules at 6 months post-irradiation (Honaramooz et al, 2005). Based on the recovery status of spermatogenesis, most studies have performed testis germ cell transplantation between 1 and 2 months post-irradiation (Kim et al, 2006;Creemers et al, 2002), and our own study revealed the optimal donor cell transfer time for irradiated sheep testis was 6 weeks after irradiation (Herrid et al, 2011).…”