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9415674 
Journal Article 
Opposite effects of high- and low-dose di-(2-ethylhexyl) phthalate (DEHP) exposure on puberty onset, oestrous cycle regularity and hypothalamic kisspeptin expression in female rats 
Yu, Z; Wang, F; Han, J; Lu, R; Li, Q; Cai, L; Li, B; Chen, J; Wang, K; Lin, W; Lin, Q; Chen, G; Wen, J 
2020 
1 
Reproduction, Fertility and Development
ISSN: 1031-3613
EISSN: 1448-5990 
CSIRO 
32 
6 
610-618 
English 
32209209 
WOS:000526397200007 
Di-(2-ethylhexyl) phthalate (DEHP) is ubiquitous in the environment and has been proposed to lead to reproductive disruption. In this study, we systematically investigated the effects of different doses of DEHP exposure on female hypothalamic-pituitary-gonadal axis development. Female Sprague-Dawley rats were gavaged with vehicle (corn oil) or DEHP (5 or 500mgkg-1 day-1) during postnatal Days (PNDs) 22-28 or PNDs 22-70. Results demonstrated that the low and high doses of DEHP exerted opposite effects on puberty onset, circulating luteinising hormone, serum oestradiol and progesterone levels, with the low dose (5mgkg-1) promoting and the high dose (500mgkg-1) inhibiting these parameters. Significant dose-related differences were also found in the D500 group with longer oestrous cycle duration, lower ovarian/bodyweight ratio, fewer corpus lutea and more abnormal ovarian stromal tissue in comparison with the oil or D5 groups. Molecular data showed that the hypothalamic Kiss1 mRNA expression in the anteroventral periventricular but not in the arcuate nucleus significantly decreased in the D500 rats and increased in the D5 rats relative to the rats in the oil group. These findings suggested that the kisspeptin system is a potential target for DEHP to disrupt reproductive development and function. 
AVPV; gonadotrophin-releasing hormone; hypothalamic-pituitary-gonadal axis; neuroendocrinological development; prepubertal exposure; reproductive function; estradiol; follitropin; gonadorelin; kisspeptin; luteinizing hormone; phthalic acid bis(2 ethylhexyl) ester; progesterone; estradiol; Kiss1 protein, rat; kisspeptin; luteinizing hormone; phthalic acid bis(2 ethylhexyl) ester; progesterone; animal cell; animal experiment; animal tissue; anteroventral cochlear nucleus; arcuate nucleus; Article; body weight; comparative study; controlled study; corpus luteum; estradiol blood level; estrus cycle; female; follitropin blood level; hypophysis gonad system; hypothalamus; luteinizing hormone blood level; male; mRNA expression level; nonhuman; perinatal period; periventricular preoptic nucleus; prenatal exposure; progeny; progesterone blood level; protein expression; puberty; rat; reproduction; reproductive toxicity; Sprague Dawley rat; animal; blood; dose response; drug effect; estrus cycle; hypothalamus; metabolism; periodicity; pollutant; reproduction; sexual development; toxicity; Animals; Diethylhexyl Phthalate; Dose-Response Relationship, Drug; Environmental Pollutants; Estradiol; Estrous Cycle; Female; Hypothalamus; Kisspeptins; Luteinizing Hormone; Periodicity; Progesterone; Rats, Sprague-Dawley; Reproduction; Sexual Development