Transplanted Bone Marrow Cells Do Not Provide New Oocytes But Rescue Fertility in Female Mice Following Treatment With Chemotherapeutic Agents

Abstract

It is generally accepted that mammalian females are born with a finite pool of oocytes and that this is the sole source of ovules throughout the reproductive life of the adult. This dogma was shaken in 2003 when researchers showed that the oocyte stock might be renewable in adult mammals. It has been proposed that hematopoietic stem cells might be a source of new oocytes. These discoveries have puzzled many researchers and remain controversial. In our study, we attempted to determine if transplanted bone marrow cells could provide new oocytes in PU.1 mice and in severe combined immunideficiency (SCID) mice after treatment with chemotherapeutic agents. We also examined the possibility that grafted bovine embryonic ovarian cortex might provide an environment favoring such a response. We found no evidence that transplanted bone marrow cells provide new fertilizable oocytes in PU.1 mice, in SCID mice treated with chemotherapeutic agents, or with bovine embryonic ovarian tissue grafts. However, transplanted bone marrow cells have improved the fertility of SCID mice previously treated with chemotherapeutic agents. These data suggest that bone marrow cells cannot provide new oocytes but can positively influence ovarian physiology to improve the fertility of mice previously treated with chemotherapeutic agents.

Study of the reparative effects of menstrual-derived stem cells on premature ovarian failure in mice

“…In recent years, interest has rapidly grown in studies exploring the therapeutic potential of stem cells because of their potential to differentiate into various specialized cell types. This characteristic has been observed in stem cells derived from a number of different sources, including bone marrow [6–8], amniotic fluid [9], and adipose tissue [10, 11], and all of these cell types have been shown to have therapeutic effects on long-term infertility and ovarian damage. However, many of the suitable cell types currently identified for human use are either difficult to obtain or obtaining them involves invasive procedures.…”

Stem Cells in Mammalian Gonads

“…They did not detect germ cell transmission from the donor. Santiquet et al (2012) transplanted BM cells in PU.1 mice and in SCID mice after treatment with chemotherapeutic agents. They found no evidence that transplanted BM cells provide new fertilizable oocytes in PU.1 mice or SCID mice.…”

Post-natal oogenesis: a concept for controversy that intensified during the last decade

“…These cells triggered the expression of the FSH receptor gene, synthesis of FSH receptors, oestrogen hormone production, and folliculogenesis in ovaries of FORKO mice (Ghadami et al, 2012). However, Santiquet et al (2012) reported that there was no evidence that BMT or bovine embryonic ovarian tissue grafts led to the production of new oocytes in PU.1 and SCDI mice following treatment by chemotherapeutic agents. Nevertheless, the influence of BM cells improved the fertility of SCID mice that had been previously exposed to chemotherapeutic agents (Santiquet et al, 2012).…”

“…However, Santiquet et al (2012) reported that there was no evidence that BMT or bovine embryonic ovarian tissue grafts led to the production of new oocytes in PU.1 and SCDI mice following treatment by chemotherapeutic agents. Nevertheless, the influence of BM cells improved the fertility of SCID mice that had been previously exposed to chemotherapeutic agents (Santiquet et al, 2012). Thus, Santiquet et al (2012) have suggested that the positive effects of transplanted bone marrow (BM) cells on the fertility of female mice could be due to renewal of self-tolerance of ovarian antigens; thereby, follicles are not demolished by chemotherapeutic agent treatment as a result of autoimmune damage.…”

“…Nevertheless, the influence of BM cells improved the fertility of SCID mice that had been previously exposed to chemotherapeutic agents (Santiquet et al, 2012). Thus, Santiquet et al (2012) have suggested that the positive effects of transplanted bone marrow (BM) cells on the fertility of female mice could be due to renewal of self-tolerance of ovarian antigens; thereby, follicles are not demolished by chemotherapeutic agent treatment as a result of autoimmune damage. Additionally, Notarianni (2011) hypothesized that chemotherapeutic treatments led to ovarian failure, cellular apoptosis and reduction of ovarian antigenspecific regulatory T cells, and eventually to an autoimmune response in the ovary (Notarianni, 2011).…”