Prenatal exposure to chromium induces early reproductive senescence by increasing germ cell apoptosis and advancing germ cell cyst breakdown in the F1 offspring

Kirthiram K. Sivakumar, Jone A. Stanley, Joe A. Arosh, Melissa E. Pepling, Robert C. Burghardt, Sakhila K. Banu

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Hexavalent chromium (CrVI), one of the more toxic heavy metals, is widely used in more than 50 industries such as chrome plating, welding, wood processing and tanneries. As one of the world's leading producers of chromium compounds, the U.S. is facing growing challenges in protecting human health against multiple adverse effects of CrVI. CrVI is rapidly converted to CrIII intracellularly, and can induce apoptosis through different mechanisms. Our previous studies demonstrated postnatal exposure to CrVI results in a delay or arrest in follicle development and puberty. Pregnant rats were treated with 25. ppm potassium dichromate (CrVI) from gestational day (GD) 9.5 to 14.5 through drinking water, placentae were removed on GD 20, and total Cr was estimated in the placentae; ovaries were removed from the F1 offspring on postnatal day (PND)-1 and various analyses were performed. Our results show that gestational exposure to CrVI resulted in (i) increased Cr concentration in the placenta, (ii) increased germ cell apoptosis by up-regulating p53/p27-Bax-caspase-3 proteins and by increasing p53-SOD-2 co-localization; (iii) accelerated germ cell cyst (GCC) breakdown; (iv) advanced primordial follicle assembly and primary follicle transition and (v) down regulation of p-AKT, p-ERK and XIAP. As a result of the above events, CrVI induced early reproductive senescence and decrease in litter size in F1 female progeny.

Original languageEnglish (US)
Pages (from-to)22-34
Number of pages13
JournalDevelopmental Biology
Volume388
Issue number1
DOIs
StatePublished - Apr 1 2014

Keywords

  • Chromium
  • Follicle atresia
  • Germ cell cyst breakdown
  • Ovary
  • Primordial follicle

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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