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Review
. 2015 Feb 2:6:8.
doi: 10.3389/fendo.2015.00008. eCollection 2015.

The effects of phthalates on the ovary

Affiliations
Review

The effects of phthalates on the ovary

Patrick R Hannon et al. Front Endocrinol (Lausanne). .

Abstract

Phthalates are commonly used as plasticizers in the manufacturing of flexible polyvinyl chloride products. Large production volumes of phthalates and their widespread use in common consumer, medical, building, and personal care products lead to ubiquitous human exposure via oral ingestion, inhalation, and dermal contact. Recently, several phthalates have been classified as reproductive toxicants and endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormone signaling. Therefore, exposure to phthalates represents a public health concern. Currently, the effects of phthalates on male reproduction are better understood than the effects on female reproduction. This is of concern because women are often exposed to higher levels of phthalates than men through their extensive use of personal care and cosmetic products. In the female, a primary regulator of reproductive and endocrine function is the ovary. Specifically, the ovary is responsible for folliculogenesis, the proper maturation of gametes for fertilization, and steroidogenesis, and the synthesis of necessary sex steroid hormones. Any defect in the regulation of these processes can cause complications for reproductive and non-reproductive health. For instance, phthalate-induced defects in folliculogenesis and steroidogenesis can cause infertility, premature ovarian failure, and non-reproductive disorders. Presently, there is a paucity of knowledge on the effects of phthalates on normal ovarian function; however, recent work has established the ovary as a target of phthalate toxicity. This review summarizes what is currently known about the effects of phthalates on the ovary and the mechanisms by which phthalates exert ovarian toxicity, with a particular focus on the effects on folliculogenesis and steroidogenesis. Further, this review outlines future directions, including the necessity of examining the effects of phthalates at doses that mimic human exposure.

Keywords: female reproductive toxicology; folliculogenesis; ovarian toxicology; ovary; phthalates; phthalic acid; steroidogenesis.

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Figures

Figure 1
Figure 1
Chemical structures of common phthalates and their monoester metabolites that are mentioned in this review.
Figure 2
Figure 2
Ovarian folliculogenesis. The female is born with a finite number of primordial follicles that can mature through the primary, preantral, and antral stages of development. The follicle contains the gamete (oocyte) surrounded by granulosa cells (shown in red) and theca cells (shown in green), which are somatic cells. Following ovulation, the antral follicle differentiates into the corpus luteum, and the granulosa and theca cells become large and small luteal cells, respectively.
Figure 3
Figure 3
Ovarian steroidogenesis. Steroidogenesis is primarily conducted by the mature antral follicle and the corpus luteum following ovulation. This process requires both the theca cells and granulosa cells, and involves the enzymatic conversion of cholesterol to 17β-estradiol and other necessary sex steroid hormones. The hormones produced by the ovary are listed in the white text boxes while the steroidogenic enzymes are listed in blue adjacent to the arrows between hormones.
Figure 4
Figure 4
Phthalates disrupt folliculogenesis. This figure is a summation of the major findings on the effects of phthalates on folliculogenesis. Text boxes above a particular follicle type outline the major effects of phthalates at that stage of development, while text boxes below transition arrows outline the major effects of phthalates on that developmental transition.
Figure 5
Figure 5
Phthalates alter steroidogenesis. This figure is a summation of the major findings on the effects of phthalates on steroidogenesis. Black text boxes connected to hormones outline the major effects of phthalates on the levels of that hormone. Blue text boxes connected to steroidogenic enzymes outline the major effects of phthalates on the mRNA and/or protein levels of that enzyme.

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