Table 3.

Phthalates effect on hypothalamic–pituitary–gonadal (HPG) axis and steroidogenesis (in vivo, in vitro experiments).

Females
Phthalates	Dose Effect (mg/kg/day)	Animal/Cell Model	Time of Exposure	Effect	References
DEHP	300	Sprague-Dawley rats	prenatal	↓ estradiol	Martinez-Arguelles et al. [173]
DEHP	1, 50, or 300	Sprague-Dawley rats	prenatal	↑ FSH	Meltzer et al. [138]
	300			↓ estradiol
DEHP	300	Sprague-Dawley rats	postnatal	↓ pregnenolone, progesterone	Nuttall et al. [174]
DEHP	30	Wistar rats	prepubertal	↑ LH	Carbone et al. [175]
DEHP	1000, and 3000	Wistar rats	postnatal	↑ GnRH	Liu et al. [132]
DEHP	3000			↓ FSH, LH, estradiol, progesterone, testosterone
DEHP	1000, and 500	Wistar rats	postnatal	↑ GnRH	Liu et al. [176]
DEHP	1, 10, 100 μg/mL	Mouse antral follicles (CD-1 mice)	postnatal	↓ progesterone, dehydroepiandrosterone, androstendione, testosterone, estradiol	Hannon et al. [121]
	1, 10, 100 μg/mL			↓ Cyp11a1
	100 μg/mL			↓ Cyp17a1
	10 μg/mL			↑ Cyp19a1, Hsd17b1
	100 μg/mL			↓ Cyp19a1, Hsd17b1
	100 μg/mL			↑ Hsd3b1
DBP	0.01, 0.1 and 1000	CD-1 mice	postnatal	↓ estradiol, ↑ FSH	Sen, Liu and Craig [177]
	1000			↓ Star, Hsd3b
	0.01, 0.1 and 1000			↓ P450scc, Cyp17a1, Hsd17b, Cyp19a1
	0.01			↑ Star, Hsd17b
DEHP	500 and 750	CD-1 mice	prenatal	↑ estradiol (F1 generation)	Brehm et al. [178]
	20			↑ estradiol (F3)
	500			↓ testosterone (F1)
	20			↓ testosterone (F2)
	20 and 500			↓ testosterone (F3)
	200			↓ progesterone (F2)
	500			↓ FSH (F1)
	500			↑ FSH (F3)
	20			↑ LH (F1)
Males
Phthalates	Dose Effect (mg/kg/day)	Animal	Time of Exposure	Effect	References
DnBP	500	Sprague-Dawley outbred CD rats	prenatal	↓ Star, Cyp11a1, Cyp17a1	Thompson et al. [179]
DEHP	100, 300, 750	Sprague-Dawley rats	prenatal	↓ testosterone	Martinez-Arguelles et al. [173]
DEHP	3 and 30	Wistar rats	prepubertal	↑ GnRH	Carbone et al. [175]
DnBP	850	Sprague-Dawley rats	prenatal	↓ Cyp11a1, Hsd3b, Star	Zhu et al. [180]
DEHP	250, 500, or 750	Sprague-Dawley rats	postnatal	↓ testosterone, FSH, LH	Ha et al. [181]
DnBP	100 and 500	Wistar rats	postnatal	↓ Hsd17b, Hsd13b	Giribabu et al [182]
				↓ testosterone, FSH, LH
DEHP	500 and 1500	Sprague-Dawley rats	postnatal	↓ GnRH	Qin et al. [183]
	100, 500, 1500			↑ Star, Hsd3b
	1500			↑ Hsd17b
DEHP	5 and 50 µg/kg/d	Long Evans rats	prenatal	↓ Hsd17b	Abdel-Maksoud, Ali and Akingbemi [184]
BBzP	10	Sprague-Dawley rats	pubertal	↑ testosterone	Lv et al. [185]
	1000			↓ testosterone
	100			↑ Cyp11a1
	10, 100 and 1000			↑ Hsd3b
DEHP	500	Crl:CD rats	postnatal	↑ Cyp4a	Yamaguchi et al. [186]

Legend: BBzP—benzylbutyl phthalate, DBP—dibutyl phthalate, DEHP—di(2-ethylhexyl) phthalate, DiNP—di-iso-nonyl phthalate, DnBP—di-n-butyl phthalate, FSH—follicle-stimulating hormone, GnRH—gonadotropin-releasing hormone, LH—luteinizing hormone.