Secretions released from mesenchymal stem cells improve spermatogenesis restoration of cytotoxic treatment with busulfan in azoospermia mice

Andrologia. 2021 Sep;53(8):e14144. doi: 10.1111/and.14144. Epub 2021 Jun 18.

Abstract

This study aimed at the efficacy of sequential treatment of bone marrow-derived mesenchymal stem cell secretion for busulfan-treated azoospermia in mice. The conditioned media (CM) was obtained from bone marrow mesenchymal stem cells (MSCs) or 293 cells. Chemically induced azoospermia mice received 200 μl MSC-CM or 293-CM twice a week intravenously for three consecutive weeks. The histological assessment of spermatogenic recovery quantifying the expression of meiosis-associated genes, and Sertoli cell barrier functional factors were assessed. The characteristics of TM4 cells (Sertoli cell line) after pre-incubation of MSC-CM in vitro were also obtained. The MSC-CM group had the most spermatogenic colonies among the three groups (p < .05), but no spermatids were seen. Expressions of the meiosis-associated genes Dazl, Vasa, Miwi, Stra8, CyclinA1, Pgk2 and Scp3 in MSC-CM testis were remarkably higher compared with 293-CM and busulfan groups respectively (p < .05). The levels of Sertoli cell barrier functional factors, for example ICAM-1 and N-cadherin, were significantly increased during MSC-CM treatment (p < .05). Moreover, pre-incubation of MSC-CM particularly accelerated the CD54 (ICAM-1) and CD44 expressions of TM4 cells and promoted cell inherent adhesion. MSC-CM treatment can significantly improve the short-term restoration of spermatogonial structures of chemically induced azoospermia related to facilitating Sertoli cell adhesion integrity.

Keywords: adhesion; azoospermia; conditioned media; meiosis-associated genes; mesenchymal stem cells.

MeSH terms

  • Animals
  • Azoospermia* / chemically induced
  • Azoospermia* / therapy
  • Busulfan / toxicity
  • Humans
  • Male
  • Mesenchymal Stem Cells*
  • Mice
  • Sertoli Cells
  • Spermatogenesis

Substances

  • Busulfan