Androgen and estrogen receptors in placental physiology and dysfunction

McWhorter, Erin S.; Russ, Jennifer E.; Winger, Quinton A.; Bouma, Gerrit J.

doi:10.1007/s11515-018-1517-z

Cited by 5 publications

(5 citation statements)

References 107 publications

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“…AR localizes to villous stromal cells, cytotrophoblast, and syncytiotrophoblast in term placenta (Iwamura, Abrahamsson, Benning, Cockett, & di Sant'Agnese, ; Horie, Takakura, Imai, Liao, & Mori, ), and previous work in our lab suggests AR is involved in regulating placental angiogenesis through its interaction with VEGFA during pregnancy (Cleys et al, ). Considering AR is a known regulator of cell proliferation and migration in cancer cells, we recently postulated this also may be true in trophoblast cells during early placental development (McWhorter, Russ, Winger, & Bouma, ). Moreover, studies in prostate cancer demonstrated that LIN28B regulates AR expression through Let‐7c miRNA (Tummala et al, ).…”

Section: Introductionmentioning

confidence: 97%

LIN28B regulates androgen receptor in human trophoblast cells through Let‐7c

McWhorter

West

Russ

et al. 2019

Molecular Reproduction Devel

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LIN28B is an RNA‐binding protein necessary for maintaining pluripotency in stem cells and plays an important role in trophoblast cell differentiation. LIN28B action on target gene function often involves the Let‐7 miRNA family. Previous work in cancer cells revealed that LIN28 through Let‐7 miRNA regulates expression of androgen receptor (AR). Considering the similarities between cancer and trophoblast cells, we hypothesize that LIN28B also is necessary for the presence of AR in human trophoblast cells. The human first‐trimester trophoblast cell line, ACH‐3P was used to evaluate the regulation of AR by LIN28B, and a LIN28B knockdown cell line was constructed using lentiviral‐based vectors. LIN28B knockdown in ACH‐3P cells resulted in significantly decreased levels of AR and increased levels of Let‐7 miRNAs. Moreover, treatment of ACH‐3P cells with Let‐7c mimic, but not Let‐7e or Let‐7f, resulted in a significant reduction in LIN28B and AR. Finally, forskolin‐induced syncytialization and Let‐7c treatment both resulted in increased expression of syncytiotrophoblast marker ERVW‐1 and a significant decrease in AR in ACH‐3P. These data reveal that LIN28B regulates AR levels in trophoblast cells likely through its inhibitory actions on let‐7c, which may be necessary for trophoblast cell differentiation into the syncytiotrophoblast.

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Section: Introductionmentioning

confidence: 97%

LIN28B regulates androgen receptor in human trophoblast cells through Let‐7c

McWhorter

West

Russ

et al. 2019

Molecular Reproduction Devel

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“…The androgen receptor (AR) is a nuclear transcription factor that mediates the expression of specific genes and is expressed in numerous target tissues, being more abundant in the male reproductive tract [ 26 ]. Hsu et al detected for the first time the presence of AR in syncytiotrophoblast and stromal cells in human normal and pre-eclamptic placentas in near-term pregnancy [ 27 ].…”

Section: Androgen Receptors In the Placenta And Umbilical Cordmentioning

confidence: 99%

“…So far, several authors have also demonstrated the presence of AR in the same cells. In the human placenta, ARs are responsible for the regulation of physiological processes such as trophoblast invasion, and differentiation into the syncytiotrophoblast, the outermost layer of the placenta [ 26 ]. The role of ARs in PE is not yet fully understood; however, altered AR levels have been observed in placenta samples, and studies have demonstrated that an overexpression of AR might be involved in the pathophysiology of PE, a pregnancy-related condition also characterized by shallow trophoblast invasion that affects proper placentation [ 27 , 28 , 29 ].…”

Section: Androgen Receptors In the Placenta And Umbilical Cordmentioning

confidence: 99%

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia

Fernandes,

Lorigo,

Cairrao

2024

CIMB

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Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health. Emerging evidence suggests an association between testosterone and pre-eclampsia (PE), potentially mediated through androgen receptors (AR). Nevertheless, the mechanism driving this association is yet to be elucidated. On the other hand, reports of transgender men’s pregnancies offer a limited and insightful opportunity to understand the role of high androgen levels in the development of HDP. In this sense, a literature review was performed from a little over 2 decades (1998–2022) to address the association of testosterone levels with the development of HDP. Furthermore, this review addresses the case of transgender men for the first time. The main in vitro outcomes reveal placenta samples with greater AR mRNA expression. Moreover, ex vivo studies show that testosterone-induced vasorelaxation impairment promotes hypertension. Epidemiological data point to greater testosterone levels in blood samples during PE. Studies with transgender men allow us to infer that exogenous testosterone administration can be considered a risk factor for PE and that the administration of testosterone does not affect fetal development. Overall, all studies analyzed suggested that high testosterone levels are associated with PE.

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“…Women with preeclampsia have elevated androgen levels and AR gene expression, and it has been hypothesized that androgens affect vascular function, and vascular smooth muscle is involved in the development of preeclampsia. Moreover, it is postulated that an abnormal levels of androgens negatively impacts placental angiogenesis and/or alters trophoblast cell proliferation and differentiation [ 13 , 14 ], although the exact mechanisms are unclear.…”

Section: Androgens and Pregnancymentioning

confidence: 99%

A Potential Role and Contribution of Androgens in Placental Development and Pregnancy

Parsons

Bouma

2021

Life

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Successful pregnancy requires the establishment of a highly regulated maternal–fetal environment. This is achieved through the harmonious regulation of steroid hormones, which modulate both maternal and fetal physiology, and are critical for pregnancy maintenance. Defects in steroidogenesis and steroid signaling can lead to pregnancy disorders or even fetal loss. The placenta is a multifunctional, transitory organ which develops at the maternal–fetal interface, and supports fetal development through endocrine signaling, the transport of nutrients and gas exchange. The placenta has the ability to adapt to adverse environments, including hormonal variations, trying to support fetal development. However, if placental function is impaired, or its capacity to adapt is exceeded, fetal development will be compromised. The goal of this review is to explore the relevance of androgens and androgen signaling during pregnancy, specifically in placental development and function. Often considered a mere precursor to placental estrogen synthesis, the placenta in fact secretes androgens throughout pregnancy, and not only contains the androgen steroid nuclear receptor, but also non-genomic membrane receptors for androgens, suggesting a role of androgen signaling in placental function. Moreover, a number of pregnancy disorders, including pre-eclampsia, gestational diabetes, intrauterine growth restriction, and polycystic ovarian syndrome, are associated with abnormal androgen levels and androgen signaling. Understanding the role of androgens in the placenta will provide a greater understanding of the pathophysiology of pregnancy disorders associated with androgen elevation and its consequences.

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Androgen and estrogen receptors in placental physiology and dysfunction

Cited by 5 publications

References 107 publications

LIN28B regulates androgen receptor in human trophoblast cells through Let‐7c

LIN28B regulates androgen receptor in human trophoblast cells through Let‐7c

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia

A Potential Role and Contribution of Androgens in Placental Development and Pregnancy

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