Potential endocrine disrupting effect of ochratoxin A on human placental 3β-hydroxysteroid dehydrogenase/isomerase in JEG-3 cells at levels relevant to human exposure

Woo, Chit Shing Jackson; Wan, Murphy Lam Yim; Ahokas, Jorma T.; El-Nezami, Hani

doi:10.1016/j.reprotox.2013.02.034

Cited by 15 publications

(13 citation statements)

References 35 publications

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“…It catalyzes the oxidation and isomerization of 5-3␤hydroxysteroid precursors into 4 -ketosteroids, first step in the biosynthesis of androgens and estrogens (Thomas et al, 1989). As 3␤-HSD1 is exclusively expressed in human placenta and plays an important role in placental steroidgenesis, modulation of placental 3␤-HSD1 activity may result in disturbance of steroid production and hence affect placental and fetal development (Woo et al, 2013). In human placenta, 3␤-HSD1 is expressed at high levels in synctial trophoblast.…”

Section: Ota and Endocrine Disruptionmentioning

confidence: 99%

“…OTA suppresses 3-hydroxysteroid dehydro-genase activity and reduces ovarian steroidogenesis in rats (Gupta et al, 1980). The induction of 3␤-HSD1 mRNA leads to an increase in progesterone production (Woo et al, 2013). It catalyzes the conversion of 3␤-hydroxy-5-ene-steroids (dihydroepiandrosterone, pregnolone) to main 3-oxo-4-enesteroids (androstendione, progesterone) to maintain the uterus in a quiescent state (Thomas et al, 1989;Kacsoh, 2000).…”

Section: Ota and Endocrine Disruptionmentioning

confidence: 99%

“…In addition to be carcinogenic, OTA has been shown to be an endocrine disruptor and a reproductive toxicant, with abilities of altering sperm quality (Biró et al, 2003;Anonymous, 2013;Woo et al, 2013). Taking into account the ubiquitous OTA occurrence in food and feed, its long half-life, and important toxicity of OTA and its metabolites (e.g., the OP-OTA, as toxic as OTA; OTHQ, more toxic than OTA; genotoxicity, carcinogenicity and in animals clearly demonstrated teratogenicity; Xiao et al, 1996;Li et al, 2000;Faucet-Marquis et al, 2006;Tozlovanu et al, 2006;Pfohl-Leszkowicz, 2009), risk management should be implemented.…”

Section: Conclusion and Recommendationsmentioning

confidence: 99%

“…Androstendione is then converted by aromatase and 17␤-hydroxysteroid dehydrogenase (17␤-HSD) to estradiol. As 3␤-HSD1 is exclusively expressed in human placenta and plays an important role in placental steroidgenesis, modulation of placental 3␤-HSD1 activity may result in disturbance of steroid production and hence affect placental and fetal development (Woo et al, 2013). To study the effects of short-and long-term OTA exposure on the expression of 3␤-HSD1 and progesterone secretions, human placental cells human choriocarcinoma cell line (JEG-3) were exposed to OTA.…”

Section: Ota and Endocrine Disruptionmentioning

confidence: 99%

“…It was shown that OTA upregulates 3␤-hydroxysteroid dehydrogenase type 1 expression in human placental cells. The induction of 3␤-HSD1 mRNA leads to an increase in progesterone production (Woo et al, 2013). OTA also induces the production of estradiol (Frizzell et al, 2013).…”

Section: Ota and Endocrine Disruptionmentioning

confidence: 99%

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Ochratoxin A: Developmental and Reproductive Toxicity—An Overview

Malíř

Ostrý

Pfohl‐Leszkowicz

et al. 2013

Birth Defects Research Pt B

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Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, reprotoxic, embryotoxic, teratogenic, neurotoxic, immunotoxic, and carcinogenic for laboratory and farm animals. Male and female reproductive health has deteriorated in many countries during the last few decades. A number of toxins in environment are suspected to affect reproductive system in male and female. OTA is one of them. OTA has been found to be teratogenic in several animal models including rat, mouse, hamster, quail, and chick, with reduced birth weight and craniofacial abnormalities being the most common signs. The presence of OTA also results in congenital defects in the fetus. Neither the potential of OTA to cause malformations in human nor its teratogenic mode of action is known. Exposure to OTA leads to increased embryo lethality manifested as resorptions or dead fetuses. The mechanism of OTA transfer across human placenta (e.g., which transporters are involved in the transfer mechanism) is not fully understood. Some of the toxic effects of OTA are potentiated by other mycotoxins or other contaminants. Therefore, OTA exposure of pregnant women should be minimized. OTA has been shown to be an endocrine disruptor and a reproductive toxicant, with abilities of altering sperm quality. Other studies have shown that OTA is a testicular toxin in animals. Thus, OTA is a biologically plausible cause of testicular cancer in man.

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Section: Ota and Endocrine Disruptionmentioning

confidence: 99%