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Infertility can be traced back to stem cells

K. S. Jayaraman

doi:10.1038/nindia.2020.139 Published online 10 September 2020

If newborn babies are exposed to chemicals that interfere with their endocrine (hormonal) systems, they could develop infertility and testicular cancer in adult life, a new study in mice1 suggests.

Infertility affects almost 8–12 per cent of couples in the reproductive age group globally but the underlying causes are not known in 40 per cent of the cases. Deepa Bhartiya, who led the study in mice at the National Institute of Research in Reproductive Health (NIRRH) in Mumbai, says infertility and reduced sperm count can possibly be traced back to endocrine disruptions that make stem cells incapable of differentiating into sperms.

Besides the actively dividing spermatogonial stem cells (SSCs), mammalian testes harbour another population of 'very small embryonic-like stem cells' (VSELs) that have remained ignored in studies till now because they are dormant and small in size, Bhartiya says. Her team, in another study2, showed the presence of VSNLs in mice testes. These testicular stem or progenitor cells are affected by endocrine disruption in newborns, their latest work shows. This may lead to infertility or testicular cancer, according to their report.

The researchers treated mice pups with the chemicals estradiol and diethylstilbestrol (DES) and studied their effect on the testicular stem cells as the mice grew into adults. They found that differentiation of VSELs/SSCs into sperms was affected with the chemicals resulting in reduced sperm count, and eventually making the mice infertile. Also the rodents exposed to DES showed excessive self-renewal of VSELs pushing them to initiate testicular cancer.

The study opens up avenues for further research to understand the underlying mechanisms that lead to unexplained (idiopathic) cases of infertility. It also seeks to explain the possible initiation of testicular cancer in mice exposed to DES in neonatal life. The researchers say the next step would be to understand the epigenetic differences between stem cells isolated from normal and cancer cells of DES-treated testes.

The investigation establishes the presence of VSELs in the mouse testes, says clinician S. G. Ananda Rao, founder of the Society of Regenerative Medicine and Tissue Engineering in Mumbai. "However, a robust functional assay should now show that these are indeed pluripotent (capable of giving rise to several different cell types) and are able to regenerate the spermatogonia," he says.


References

1. Kaushik, A. et al. Altered biology of testicular VSELs and SSCs by neonatal endocrine disruption results in defective spermatogenesis, reduced fertility and tumor initiation in adult mice. Stem Cell Rev. Rep. (2020) doi: 10.1007/s12015-020-09996-3

2. Kaushik, A. & Bhartiya, D. (2020) Additional evidence to establish existence of two stem cell populations including VSELs and SSCs in adult mouse testes. Stem Cell Rev. Rep. (2020) doi: 10.1007/s12015-020-09993-6