Abstract
Very small embryonic-like stem cells (VSELs) are pluripotent stem cells present in various adult body tissues, maintain life-long tissue homeostasis and are possibly the embryonic remnants responsible for cancers. Neonatal exposure to endocrine disruptors is a serious problem and is implicated with several diseases in adults like PCOS in women, infertility in men and increased incidence of endocrine cancers etc. Thus it was of interest to investigate whether VSELs are affected by exposure to endocrine disruptors. Mice pups were injected 20 μg of 17β-estradiol daily on days 5-7 and were sacrificed after 100 days. Testes, ovaries, uteri and prostate tissues were collected and processed for histology and RNA extraction. Testicular sections were also used to immuno-localize PCNA and DAZL, markers that reflect proliferation and germ cell population. Quantitative RT-PCR analysis was performed for Oct-4A and Sca-1, specific markers for VSELs. Histological studies showed PCO-like condition in ovaries, spermatogenesis was affected and both uterus and prostate showed early signs of cancer including hypertrophied and multilayered epithelium, absent glands in the uterus and acute inflammation in prostate. Increased PCNA and DAZL positive cells were detected in the treated testicular sections. Oct-4A and Sca-1 transcripts were detected in all organs and showed increased expression in ovary and testis. Bilateral germ cell tumor was observed in one out of ten treated mice and histological studies showed complete absence of seminiferous tubules and sperm; however VSELs were detected and confirmed by the presence of Oct-4A and Sca-1 transcripts. Present study provides evidence for the first time that neonatal exposure to estrogens results in altered VSELs function in favor of aberrant proliferation rather than differentiation leading to increased risk of cancers. Altered VSELs function possibly due to compromised somatic microenvironment (by neonatal exposure to endocrine disruptors) results in adult onset of various diseases including hormone-sensitive cancers.
DOI: 10.14343/JCSCR.2013.1e1003