Marvin L. Meistrich, PhD, Oral History Interview, May 2, 2017

Major Topics Covered: Personal background Educational path Research: spermatid nuclear proteins, spermatogenesis, impact of chemotherapy on oncofertility; cryopreservation and transplantation Attitudes toward addressing issues of oncofertility and sperm banking at MD Anderson Research culture The Department of Experimental Radiation Oncology, history of Institutional change and growth Retirement processhttps://openworks.mdanderson.org/mchv_interviewsessions/1165/thumbnail.jp

Marvin L. Meistrich, PhD, Oral History Interview, April 11, 2017

Major Topics Covered: Personal background Educational path Research: spermatid nuclear proteins, spermatogenesis, impact of chemotherapy on oncofertility; cryopreservation and transplantation Attitudes toward addressing issues of oncofertility and sperm banking at MD Anderson Research culture The Department of Experimental Radiation Oncology, history of Institutional change and growth Retirement processhttps://openworks.mdanderson.org/mchv_interviewsessions/1164/thumbnail.jp

Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche.

A major challenge in stem cell differentiation is the availability of bioassays to prove cell types generated in vitro are equivalent to cells in vivo. In the mouse, differentiation of primordial germ cell-like cells (PGCLCs) from pluripotent cells was validated by transplantation, leading to the generation of spermatogenesis and to the birth of offspring. Here we report the use of xenotransplantation (monkey to mouse) and homologous transplantation (monkey to monkey) to validate our in vitro protocol for differentiating male rhesus (r) macaque PGCLCs (rPGCLCs) from induced pluripotent stem cells (riPSCs). Specifically, transplantation of aggregates containing rPGCLCs into mouse and nonhuman primate testicles overcomes a major bottleneck in rPGCLC differentiation. These findings suggest that immature rPGCLCs once transplanted into an adult gonadal niche commit to differentiate towards late rPGCs that initiate epigenetic reprogramming but do not complete the conversion into ENO2-positive spermatogonia

Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice

<div><p>Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. <i>In utero</i> exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼70% of control and induced atrophic seminiferous tubules in ∼30% of the testes. When the <i>in utero</i> CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents <i>in utero</i> may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.</p></div

The New Director of “the Spermatogonial Niche”: Introducing the Peritubular Macrophage

In this issue of Cell Reports, DeFalco et al. (2015) characterize a novel macrophage population associated with the peritubular lamina of mouse testes. These macrophages may create a niche not for the self-renewal of stem cells but rather the induction of their differentiation