Placental steroidogenesis in pregnant women with polycystic ovary syndrome

Maliqueo, Manuel; Lara, Hernán E.; Sánchez, Francisco Javier Sierro; Echiburú, Bárbara; Crisosto, Nicolás; Sir-Petermann, Teresa

doi:10.1016/j.ejogrb.2012.10.015

Cited by 175 publications

(157 citation statements)

References 27 publications

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“…A recent study aimed to evaluate the placental activities of steroid sulfatase (STS), 3b-hydroxysteroid dehydrogenase type 1 (3b-HSD-1) and P450 aromatase (P450arom) in PCOS compared to normal pregnant women. The data suggest that placental tissue from women with PCOS shows changes in the activities of two important enzymes for steroid synthesis: higher 3b-HSD-1 and lower P450arom which would indicate increased androgen production during pregnancy (45). In line with our findings, Maliqueo et al (45) found that cord blood of the female offspring from the PCOS mothers did not contain elevated androgens, and even had lower ADION and higher E 3 concentrations (although androgens during pregnancy were elevated).…”

Section: Discussionsupporting

confidence: 80%

“…Remarkably, Anderson and Maliqueo, as we did, also found significantly lower ADION concentrations in cord blood of female offspring of the PCOS women, as compared to the female offspring of non-PCOS women (43,45). To our knowledge only Barry et al (47) reported elevated T concentrations in cord blood in PCOS daughters compared to controls.…”

Section: Discussionmentioning

confidence: 64%

“…The present and previous studies (43,44,45,46) show that elevated androgen concentrations during pregnancy in PCOS women, do not contribute to elevated androgens in cord blood. Remarkably, Anderson and Maliqueo, as we did, also found significantly lower ADION concentrations in cord blood of female offspring of the PCOS women, as compared to the female offspring of non-PCOS women (43,45).…”

Section: Discussionmentioning

confidence: 73%

“…Remarkably Maliqueo et al also found lower E 1 concentrations in PCOS cord blood from daughters compared to controls (PZ0.061). It is possible that placental steroidogenesis follows different pathways in PCOS mothers which result in a different ratio of estrogen fractions during gestation and in their offspring (45).…”

Section: Discussionmentioning

confidence: 99%

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Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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Objective: Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls. Design: Prospective case-control study. Methods: Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E 1 ), estradiol (E 2 ), estriol (E 3 )) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Results: At 20 weeks of gestation: T (PZ0.019) and ADION (PZ0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E 1 , E 2 , and E 3 were not different. Maternal concentration at birth: T (PZ0.004) and ADION (PZ0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E 1 , E 2 and E 3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E 2 , E 3 , and AMH between the PCOS mothers and the controls respectively. E 1 was lower in girls from PCOS mothers (PZ0.007). Conclusions: Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Caanen

Kuijper

Hompes

et al. 2016

European Journal of Endocrinology

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show abstract

“…Since excess of testosterone may be seen as an endocrine disruptor as well as an environmental disruptor (Skakkebaek et al 2001), these findings in our animal model could, although with caution, be extended to human reproductive health, in particular, to sons of pregnant PCOS women. In support of this premise, placentas from PCOS mothers were found to have lower aromatase and higher 3b-HSD1 activities, which could lead to increased androgen levels during pregnancy (Maliqueo et al 2013). The studies of Veiga-Lopez et al (2011) in sheep have found male and female sheep fetuses whose mothers were administered testosterone to have elevated plasma testosterone levels compared with their control counterparts.…”

Section: Effect Of Prenatal Testosterone Excess On Gonadal Testosteromentioning

confidence: 88%

Pituitary and testis responsiveness of young male sheep exposed to testosterone excess during fetal development

Recabarren¹,

Rojas-García²,

Einspanier³

et al. 2013

Reproduction

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Prenatal exposure to excess testosterone induces reproductive disturbances in both female and male sheep. In females, it alters the hypothalamus-pituitary-ovarian axis. In males, prenatal testosterone excess reduces sperm count and motility. Focusing on males, this study tested whether pituitary LH responsiveness to GNRH is increased in prenatal testosterone-exposed males and whether testicular function is compromised in the testosterone-exposed males. Control males (nZ6) and males born to ewes exposed to twice weekly injections of 30 mg testosterone propionate from days 30 to 90 and of 40 mg testosterone propionate from days 90 to 120 of gestation (nZ6) were studied at 20 and 30 weeks of age. Pituitary and testicular responsiveness was tested by administering a GNRH analog (leuprolide acetate). To complement the analyses, the mRNA expression of LH receptor (LHR) and that of steroidogenic enzymes were determined in testicular tissue. Basal LH and testosterone concentrations were higher in the testosterone-exposed-males. While LH response to the GNRH analog was higher in the testosterone-exposed males than in the control males, testosterone responses did not differ between the treatment groups. The testosterone:LH ratio was higher in the control males than in the testosterone-exposed males of 30 weeks of age, suggestive of reduced Leydig cell sensitivity to LH in the testosterone-exposed males. The expression of LHR mRNA was lower in the testosterone-exposed males, but the mRNA expression of steroidogenic enzymes did not differ between the groups. These findings indicate that prenatal testosterone excess has opposing effects at the pituitary and testicular levels, namely increased pituitary sensitivity to GNRH at the level of pituitary and decreased sensitivity of the testes to LH.

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Overactivation of the androgen receptor exacerbates gravid uterine ferroptosis via interaction with and suppression of the NRF2 defense signaling pathway

Zhang

et al. 2022

FEBS Letters

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The mechanisms through which the androgen-dependent activation of the androgen receptor (AR) regulates gravid uterine ferroptosis remain unknown. We show that while co-exposure of pregnant rats to the androgen 5adihydrotestosterone (DHT) and insulin (INS) triggered uterine ferroptotic signaling cascades, additional treatment with the anti-androgen flutamide increased expression of the key ferroptosis-inhibitory proteins SLC7A11, GSH, and GPX4; reduced iron content; normalized levels of ferroptosisassociated Tfrc, Fpn1, and Ho1 mRNAs; reduced levels of proteins modified by 4-HNE (a marker of ferroptosis); and restored protein levels of NRF2, a key transcription factor regulating antioxidant defense signaling, in the gravid uterus. Furthermore, exposure to DHT alone increased uterine ferroptosis, and NRF2 abundance was negatively correlated with AR status. Coimmunoprecipitation and Western blot assays revealed that the AR physically interacted with endogenous NRF2, and this interaction was increased by DHT exposure in vivo. Our results suggest that AR overactivation and NRF2 suppression cooperate in the regulation of NRF2-targets in uterine ferroptosis.

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Placental steroidogenesis in pregnant women with polycystic ovary syndrome

Cited by 175 publications

References 27 publications

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

Pituitary and testis responsiveness of young male sheep exposed to testosterone excess during fetal development

Overactivation of the androgen receptor exacerbates gravid uterine ferroptosis via interaction with and suppression of the NRF2 defense signaling pathway

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