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Review
. 2022 Feb 25;23(5):2559.
doi: 10.3390/ijms23052559.

Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?

Nolwenn Adam  1 , Sakina Mhaouty-Kodja  1
Affiliations
Review

Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?

Nolwenn Adam et al. Int J Mol Sci. .

Abstract

Phthalates have been widely studied for their reprotoxic effects in male rodents and in particular on testosterone production, for which reference doses were established. The female rodent brain can also represent a target for exposure to these environmental endocrine disruptors. Indeed, a large range of behaviors including reproductive behaviors, mood-related behaviors, and learning and memory are regulated by sex steroid hormones. Here we review the experimental studies addressing the effects and mechanisms of phthalate exposure on these behaviors in female rodents, paying particular attention to the experimental conditions (period of exposure, doses, estrous stage of analyses etc.). The objective of this review is to provide a clear picture of the consistent effects that can occur in female rodents and the gaps that still need to be filled in terms of effects and mode(s) of action for a better risk assessment for human health.

Keywords: behavior; endocrine disruptor; nervous system; phthalate; reproduction; sex steroids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A). In females, the ovaries start synthesizing and liberating sex steroids from postnatal day 7. During the postnatal/prepubertal and pubertal periods, sex steroids play an important role in the organization of neural structures involved in the regulation of the gonadotropic axis and behaviors. During adulthood, sex steroids play an activation role. (B). Kisspeptin neurons from the RP3V and arcuate nucleus project on GnRH neurons, thereby stimulating GnRH liberation, which acts on the pituitary to stimulate the liberation of LH and FSH and consequently the ovarian secretion of gonadal hormones. In turn, sex steroids exert positive or negative feedbacks on kisspeptin neurons and the pituitary. (C). Ovarian sex steroids act on the brain to activate the neural structures underlying the mentioned behaviors. RP3V, rostral periventricular area of the third ventricle; GnRH, Gonadotropin-Releasing Hormone; LH, Luteinizing Hormone; FSH, Follicle Stimulating Hormone.
Figure 2
Figure 2
Summary information on the experimental conditions used in the studies discussed in the present review. DEHP, Di-(2-ethylexyl) phthalate; DBP, Dibutyl phthalate; DINP, Diisononyl phthalate; BBP, Benzyl butyl phthalate; DEHA, Di-(2-ethylhexyl) adipate; NOAEL, non-observed adverse effect level.
See this image and copyright information in PMC

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