Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy

Albrecht, Eugene D.; Pepe, Gerald J.

doi:10.1387/ijdb.082758ea

Cited by 134 publications

(66 citation statements)

References 166 publications

(178 reference statements)

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“…Furthermore, estrogen stimulates angiogenesis, which is a critical process for placental function, by regulating vascular endothelial growth factor (VEGF) and growth of endothelial cells in the placenta. Therefore, abnormal estrogen levels and angiogenesis in the placenta are associated with complications such as preeclampsia and preterm delivery (Albrecht & Pepe 2010).…”

Section: Introductionmentioning

confidence: 99%

Interaction of steroid receptor coactivators and estrogen receptors in the human placenta

Kim¹,

Park²,

Lee³

et al. 2016

Journal of Molecular Endocrinology

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Female sex steroid hormones such as estrogen and progesterone have a pivotal role in maintaining pregnancy in human and animals. Especially, estrogen exerts specific effects on the cardiovascular system and angiogenesis, and thus affects significantly on placentation. Although the functions of estrogen have been emphasized during pregnancy, their signaling pathways in the placenta have not been fully understood. In this study, estrogen signaling was evaluated according to gestational age. Human placenta samples were collected and divided into early preterm (n = 10), late preterm (n = 18), and term (n = 20) groups. First, serum estrogen concentration and corticotropinreleasing hormone (CRH) mRNA expression, which is known as gestation clock gene, were increased following gestation age in our experimental condition, as we expected. Next, the expression of estrogen receptors (ERs) and steroid receptor coactivators (SRCs) in the placenta was evaluated. ERα (ESR1) and ERβ (ESR2) were expressed highly at term period compared with early preterm. In addition, SRC family including SRC1, SRC2, and SRC3 was expressed in the human placenta, and the levels of SRC1, SRC2, and SRC3 were increased in the placenta at the late stage of gestation. The interaction of ERs with SRCs was also examined, which was significantly enhanced at term period. In the immunostaining results, it was indicated that ERs and SRCs were all dominantly expressed in syncytiotrophoblast cells. These results suggested that SRC1, SRC2, and SRC3 were expressed and interact with ERs highly at the late stage of gestation, and may amplify the signaling of estrogen in the placenta to maintain pregnancy.

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Section: Introductionmentioning

confidence: 99%

Interaction of steroid receptor coactivators and estrogen receptors in the human placenta

Kim¹,

Park²,

Lee³

et al. 2016

Journal of Molecular Endocrinology

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“…Estrogens formed by placental aromatase may enhance angiogenesis, uteroplacental blood flow, and reduce systemic vascular resistance (10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia

Zhang

Muralimanoharan

Wortman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dysregulation of human trophoblast invasion and differentiation can result in preeclampsia (PE), a hypertensive disorder of pregnancy with significant morbidity and mortality for mother and offspring. miRNA microarray analysis of RNA from human cytotrophoblasts (CytT), before and after differentiation to syncytiotrophoblast (SynT) in primary culture, revealed that members of miR-515 family-including miR-515-5p, miR-519e-5p, miR-519c-3p, and miR-518f, belonging to the primate-and placenta-specific chromosome 19 miRNA cluster (C19MC)-were significantly down-regulated upon human SynT differentiation. The proto-oncogene, c-MYC, which declines during SynT differentiation, interacted with E-boxes upstream of pri-miR-515-1 and pri-miR-515-2, encoding these mRNAs, to enhance their expression. Predicted targets of miR-515-5p, known to be critical for human SynT differentiation, including hCYP19A1/aromatase P450, glial cells missing 1 (GCM1), frizzled 5 (FZD5), WNT2, Sp1, and estrogen receptor-α (ERα) mRNA, were markedly up-regulated during SynT differentiation. Notably, overexpression of miR-515-5p in cultured primary human trophoblasts impaired SynT differentiation and specifically decreased expression of hCYP19A1, GCM1, and Fzd5, which were validated as its direct targets. Interestingly, miR-515-5p levels were significantly increased in PE placentas, whereas mRNA and protein levels of targets, hCYP19A1, GCM1, and FZD5, were significantly decreased, compared with placentas of normotensive women. Thus, miR-515-5p may serve a key role in human trophoblast differentiation; its aberrant up-regulation may contribute to the pathogenesis of PE.human placenta | differentiation | miRNAs | aromatase | Wnt signaling

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“…Estrone is further converted into more potent estrogen, estradiol, by 17β-hydroxysteroid dehydrogenase isoforms (HSD17B1, HSD17B7 and HSD17B12) [2] . Placental estradiol stimulates placental growth and enhances placental blood flow to provide the optimal exchange of gases and nutrients required for the rapidly developing fetus [3] .…”

Section: Effects Of Methoxychlor and Itsmentioning

confidence: 99%

Effects of Methoxychlor and Its Metabolite Hydroxychlor on Human Placental 3β-Hydroxysteroid Dehydrogenase 1 and Aromatase in JEG-3 Cells

Liu¹,

Mao²,

Bai

et al. 2016

Pharmacology

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Progesterone and estradiol produced by the human placenta are critical for maintenance of pregnancy and fetal development. In the human placenta, 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) is responsible for the formation of progesterone from pregnenolone and aromatase (CYP19A1) for the production of estradiol from androgen. Insecticide methoxychlor (MXC) and its metabolite hydroxychlor (HPTE) may disrupt the activities of these 2 enzymes. In this study, we investigated the effects of MXC and HPTE on steroid production in human placental JEG-3 cells and on HSD3B1 and CYP19A1 activities. MXC and HPTE inhibited progesterone and estradiol production in JEG-3 cells. MXC and HPTE were potent HSD3B1 inhibitors with the half maximal inhibitory concentration (IC₅₀) values of 2.339 ± 0.096 and 1.918 ± 0.078 μmol/l, respectively. MXC had no inhibition on CYP19A1 at 100 μmol/l, while HPTE was a weak inhibitor with IC₅₀ of 97.16 ± 0.10 μmol/l. When pregnenolone was used to determine the inhibitory mode, MXC and HPTE were found to be competitive inhibitors of HSD3B1. When cofactor NAD⁺ was used, MXC and HPTE were the noncompetitive inhibitors of HSD3B1. When testosterone was used, HPTE was a mixed inhibitor of CYP19A1. In conclusion, MXC and HPTE are potent inhibitors of human HSD3B1, and HPTE is a weak CYP19A1 inhibitor.

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Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy

Cited by 134 publications

References 166 publications

Interaction of steroid receptor coactivators and estrogen receptors in the human placenta

Interaction of steroid receptor coactivators and estrogen receptors in the human placenta

Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia

Effects of Methoxychlor and Its Metabolite Hydroxychlor on Human Placental 3β-Hydroxysteroid Dehydrogenase 1 and Aromatase in JEG-3 Cells

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