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10 August 2016 Estrogenic Compounds Impair Primordial Follicle Formation by Inhibiting the Expression of Proapoptotic Hrk in Neonatal Rat Ovary
Haolin Zhang, Kentaro Nagaoka, Kento Usuda, Kaori Nozawa, Kazuyoshi Taya, Midori Yoshida, Gen Watanabe
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Abstract

Exposure to endocrine-disrupting chemicals (EDCs) during fetal and neonatal periods can have toxic effects that are irreversible and last a lifetime. However, the mechanism underlying this phenomenon is still unknown. Here, we show the effect of 17alpha-ethynyl estradiol (EE) on the development of the primordial follicle during early ovarian development in female rats. Microarray analysis revealed the down-regulation of Hrk, an activator of apoptosis, in neonatal ovaries exposed to EE. Real-time PCR analysis also showed a decrease of Hrk mRNA expression in ovaries treated with EE both in vitro and in neonatal rats. An immunostaining assay showed that HRK protein and cleaved caspase 3 colocalize in the oocytes at Postnatal Day 1 (PND1). The EE-exposed ovaries had a reduced number of oocytes positive for TUNEL staining compared to control ovaries at PND1. Abnormal follicle formation of EE-exposed ovaries was observed at PND7 and PND21. A TUNEL staining assay revealed that Hrk depletion reduced the number of apoptotic oocytes. In addition, down-regulation of Hrk mRNA expression was observed in ovaries treated with other estrogenic chemicals. We propose a model in which EE inhibits oocyte apoptosis in the neonatal ovary by suppressing the expression of Hrk, thereby disrupting follicle formation and ovary function.

Haolin Zhang, Kentaro Nagaoka, Kento Usuda, Kaori Nozawa, Kazuyoshi Taya, Midori Yoshida, and Gen Watanabe "Estrogenic Compounds Impair Primordial Follicle Formation by Inhibiting the Expression of Proapoptotic Hrk in Neonatal Rat Ovary," Biology of Reproduction 95(4), (10 August 2016). https://doi.org/10.1095/biolreprod.116.141309
Received: 19 April 2016; Accepted: 1 July 2016; Published: 10 August 2016
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KEYWORDS
17alpha-ethynylestradiol
endocrine-disrupting chemicals
Hrk
neonate
ovary
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