Human umbilical cord mesenchymal stem cells (hUC-MSCs) alleviate paclitaxel-induced spermatogenesis defects and maintain male fertility

Abstract

Chemotherapeutic drugs can cause reproductive damage by affecting sperm quality and other aspects of male fertility. Stem cells are thought to alleviate the damage caused by chemotherapy drugs and to play roles in reproductive protection and treatment. This study aimed to explore the effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on alleviating paclitaxel (PTX)-induced spermatogenesis and male fertility defects. An in vivo PTX-induced mice model was constructed to evaluate the reproductive toxicity and protective roles of hUC-MSCs in male fertility improvement. A 14 day PTX treatment regimen significantly attenuated mice spermatogenesis and sperm quality, including affecting spermatogenesis, reducing sperm counts, and decreasing sperm motility. hUC-MSCs treatment could significantly improve sperm functional indicators. Mating experiments with normal female mice and examination of embryo development at 7.5 days post-coitum (dpc) showed that hUC-MSCs restored male mouse fertility that was reduced by PTX. In IVF experiments, PTX impaired sperm fertility and blastocyst development, but hUC-MSCs treatment rescued these indicators. hUC-MSCs’ protective role was also displayed through the increased expression of the fertility-related proteins HSPA2 and HSPA4L in testes with decreased expression in the PTX-treated group. These changes might be related to the PTX-induced decreases in expression of the germ cell proliferation protein PCNA and the meiosis proteins SYCP3, MLH1, and STRA8, which were restored after hUC-MSCs treatment. In the PTX-treated group, the expression of testicular antioxidant proteins SIRT1, NRF2, CAT, SOD1, and PRDX6 was significantly decreased, but hUC-MSCs could maintain these expressions and reverse PTX-related increases in BAX/BCL2 ratios. hUC-MSCs may be a promising agent with antioxidant and anti-apoptosis characteristics that can maintain sperm quality following chemotherapy treatment.

Stem Cells and Infertility: A Review of Clinical Applications and Legal Frameworks

“…Chemotherapeutic drugs can cause reproductive damage due to their gonadotoxic effects on sperm quality and other aspects of male fertility. The study by Zhang Y et al focuses on showing how stem cells can reportedly alleviate the damage caused by chemotherapy drugs and to play roles in reproductive protection and treatment [115]; this was conducted in order to investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-derived exosomes) can repair injured endometrial epithelial cells (EECs) and reduce their death, and exhibit an anti-inflammatory effect against OGD/R (oxygen and glucose deprivation/reoxygenation) [116]. As reported in 2016 by multiple groups, scientists developed the ability to culture human embryos for 12 or 13 days [117], and in light of such developments, ethicists have called for the policy to be reconsidered, with some even suggesting that research should be allowed until the 21st or 28th day after fertilization [118].…”

Stem Cells and Infertility: A Review of Clinical Applications and Legal Frameworks

“…Chemotherapeutic drugs can cause reproductive damage due its gonadotoxyc effects on sperm quality and other aspects of male fertility. Zhang Y et al focus their study showing how stem cells are thought to alleviate the damage caused by chemotherapy drugs and to play roles in reproductive protection and treatment [98], in order to investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-derived exosomes) can repair injured endometrial epithelial cells (EECs) and reduce their death, and exhibit an anti-inflammatory effect against OGD/R (oxygen and glucose deprivation/reoxygenation) [99]. As reported in 2016 by multiple groups, scientists developed the ability to culture human embryos for 12 or 13 days [100], ethicists have also called for the policy to be revisited, and some have suggested that research should be allowed until the 21 st or 28 th day after fertilization [101].…”