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Assessing Prenatal and Neonatal Gonadal Steroid Exposure for Studies of Human Development: Methodological and Theoretical Challenges

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196074 Year: Pages: 80 DOI: 10.3389/978-2-88919-607-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2016-08-16 10:34:25
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Abstract

There is extensive evidence from animal models that gonadal steroids, produced in fetal and neonatal life, act on the developing organism to produce sex differences far beyond the reproductive system. That early gonadal steroid exposure also plays an important role in human development is supported by studies of individuals with disorders of sex determination and differentiation. It is much less clear whether normal variation in gonadal steroid exposure predicts sexually dimorphic health outcomes or within-sex variation. This is largely due to challenges related to the assessment of gonadal steroid exposure in the developing fetus and neonate. Regarding the prenatal period, serial measurements of serum hormone levels in the fetus, for use in studies of later development, are not possible for ethical reasons. Researchers have measured hormones in maternal blood, umbilical cord blood, and amniotic fluid; used putative anthropometric indices such as the relative lengths of the 2nd and 4th digits (2D:4D); evaluated common variants in genes related to hormone production, transport, and metabolism; and examined development in opposite sex twins and the offspring of mothers with hyperandrogeny. Each of these approaches has particular strengths and notable weaknesses. Regarding the neonatal period, serial measurements in serum are often impractical for studies of typical development. Salivary hormone assays, frequently used in studies of older children and adults, have not been extensively investigated in neonates. The most appropriate timing for testing is also open to debate. Early work suggested that testosterone levels in males begin to rise after the first postnatal week, peak around the 3rd to 4th months of life, and then drop back to very low levels by 1 year. However a more recent study of 138 infants did not demonstrate this pattern. Testosterone was highest on the day of birth and gradually dropped over the first 6 months. Even less is known about patterns of early estrogen exposure, though highly sensitive bioassays indicated that sex differences are present in early childhood. In addition, the design and interpretation of studies may be impacted by widespread acceptance of conceptual frameworks that are not well-supported empirically. For example, many researchers presume that the free hormone hypothesis, which states that unbound hormone is more readily diffusible into tissues and thus a better measure of actual exposure, is true. However this hypothesis has been challenged on multiple grounds. A second example: it is generally accepted that masculinization of the human brain is primarily mediated by the androgen receptor (in contrast to rodents where the estrogen receptor plays a major role), in part because chromosomal males with complete androgen insensitivity generally espouse a female gender identity. However this is not always the case, and other sexually dimorphic outcomes have not been carefully assessed in CAIS. The aim of this research topic is to gather together experimental and review papers which address the diverse challenges in assessing prenatal and neonatal gonadal steroid exposure for studies of human development with the expectation that this will allow more critical appraisal of existing studies, identify critical research gaps, and improve the design of future studies.

The Roles of GnIH in Reproductive Function and Behavior

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454426 Year: Pages: 128 DOI: 10.3389/978-2-88945-442-6 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2018-11-16 17:17:57
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Since the discovery of gonadotropin-releasing hormone (GnRH) at the beginning of 1970s, it has been believed that GnRH is the only hypothalamic neuropeptide that regulates gonadotropin release in vertebrates. In 2000, however, a novel hypothalamic neuropeptide that actively inhibits gonadotropin release was discovered in Japanese quail and termed gonadotropin-inhibitory hormone (GnIH). Following seventeen years of research has revealed that GnIH is highly conserved across vertebrates including humans, and GnIH is involved in a number of physiological and behavioral functions related to reproduction. The aim of this e-book is to celebrate the discovery of GnIH and the progress of GnIH research by collecting review and original articles from leading scientists in this new research field.

Molecular Research of Endometrial Pathophysiology

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ISBN: 9783039214952 / 9783039214969 Year: Pages: 378 DOI: 10.3390/books978-3-03921-496-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Social Sciences --- Sociology
Added to DOAB on : 2019-12-09 16:10:12
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The endometrium has been the subject of intense research in a variety of clinical settings, because of its importance in the reproductive process and its role in women’s health. In the past 15 years, significant efforts have been invested in defining the molecular phenotype of the receptive phase endometrium as well as of various endometrial pathologies. Although this has generated a wealth of information on the molecular landscape of human endometrium, there is a need to complement this information in light of the novel methodologies and innovative technical approaches. The focus of this International Journal of Molecular Sciences Special Issue is on molecular and cellular mechanisms of endometrium and endometrium-related disorders. The progress made in the molecular actions of steroids, in the metabolism of steroids and intracrinology, in endometrial intracellular pathways, in stem cells biology, as well as in the molecular alterations underlying endometrium-related pathologies has been the focus of the reviews and papers included.

Keywords

RANK --- endometrium --- endometrial cancer --- prognosis --- immunohistochemistry --- gene expression --- endometriosis --- developmental pathway --- pathogenomics --- mesenchymal stem cells --- endometrial cancer --- mtDNA mutations --- deficit of complex I --- antioxidant response --- mitochondrial biogenesis --- mitochondrial dynamics --- mitophagy --- miRNA --- lncRNAs --- endometrial cancer --- endometriosis --- chronic endometritis --- cell contacts --- tight junction --- adherens junction --- gap junction --- endometrium --- implantation --- decidualization --- endometriosis --- endometrial cancer --- liquid biopsy --- uterine aspirate --- circulating tumour cells (CTCs) --- circulating tumour DNA (ctDNA) --- exosomes --- Vitamin D --- endometrium --- endometrial cancer --- endometrial cancer --- preclinical models --- translational research --- endometrial cancer --- type II endometrial carcinoma --- targeted therapy --- kinase inhibitor --- molecular marker --- protein kinase --- protein phosphatase --- PP2A --- PPP2R1A --- SMAP --- endometriosis --- infertility --- niche --- inflammation --- immunomodulation --- mesenchymal stem cell --- orthoxenograft --- uterine cancer --- avatar --- murine models --- personalized medicine --- targeted therapy --- preclinical studies --- translational research --- endometriosis --- TRP channels --- endometrial stromal cells --- eutopic and ectopic endometrium --- endometrial cell --- pathway --- proliferation --- decidualization --- migration --- angiogenesis --- regeneration --- breakdown --- implantation --- endometrial cancer --- orthotopic xenograft model --- estrogen dependent --- bioluminescence imaging --- contrast-enhanced CT scan --- endometrium --- adult stem cells --- endometrial regeneration --- stem cell markers --- endometriosis --- endometrial cancer --- decidualisation --- oestradiol --- aromatase --- testosterone --- dehydroepiandrosterone (DHEA) --- endometriosis --- endometrial cancer --- sulfatase --- endometriosis --- ectopic stroma --- microRNA --- small RNA sequencing --- EDN1 --- HOXA10 --- miR-139-5p --- miR-375 --- CTCF --- tumour suppressor gene --- haploinsufficiency --- zinc finger --- CRISPR/Cas9 --- cancer --- endometrial cancer --- gene editing --- phosphoinositide 3-kinase --- PIK3CA --- PIK3CB --- p110? --- p110? --- endometrial cancer --- LGR5 --- endometrium --- endometriosis --- menstrual cycle --- macrophages

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