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Growth factors and estrogen receptor (ER) signaling cooperate to play essential roles in cell proliferation, differentiation and tumor progression in mouse reproductive organs. Treatment of neonatal mice with diethylstilbestrol (DES) induces an estrogen-independent persistent proliferation and cornification of the vaginal epithelium, which results in cancerous lesions later in life. However, the mechanisms of the estrogen-dependent and -independent pathways essentially remain unknown. We characterized the expression of epidermal growth factor (EGF)-like growth factors (EGF, transforming growth factor alpha (TGF-alpha), heparin-binding EGF-like growth factor (HB-EGF), betacellulin (BTC), amphiregulin (APR), epiregulin (EPR) and neuregulin (NRG) 1) and erbB receptors (EGF receptor (EGFR), erbB2/neu, erbB3 and erbB4) in the vaginae of mice treated either neonatally (0-4 day) or as adults (55-59 day) with estrogens. EGFR and erbB2 were activated in the vaginal epithelium of mice by estrogen treatment. This activation was also encountered in vaginae from neonatally DES-exposed mice, along with the expression of EGF, TGF-alpha, HB-EGF, BTC, APR, EPR and NRG1. Immunohistochemical analysis indicated that erbB2 was primarily expressed in vaginal epithelium. Finally, we found that serine 118 and 167 located in the AF-1 domain of ERalpha were phosphorylated in these vaginae. AG825, AG1478 or ICI 182,780 administration blocked proliferation of vaginal epithelium induced by neonatal DES exposure. Thus, signal transduction via EGFR and erbB2 could be related to the estrogen-induced vaginal changes and persistent erbBs phosphorylation and sustained expression of EGF-like growth factors, leading to ERalpha activation that may result in cancerous lesions in vaginae from neonatally DES-exposed mice later in life.
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http://dx.doi.org/10.1038/sj.onc.1207207 | DOI Listing |
Microb Pathog
December 2024
Department of Neonatology, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong Province, 518107, China. Electronic address:
Background: Streptococcus agalactiae poses a significant threat to neonatal health, causing morbidity and mortality when transmitted from the maternal vagina to the newborn's respiratory tract. Among its various strains, serotype III is predominant in severe neonatal infections in Asia. However, the mechanisms of pathogenesis and host responses underlying serotype-specific disease outcomes remain poorly understood.
View Article and Find Full Text PDFAm J Reprod Immunol
December 2024
NISE Laboratory, School of Psychology, Faculty of Social Science, University of Ottawa, Ottawa, Ontario, Canada.
The human vaginal microbiome (VMB) is a complex and unique ecosystem composed of various microorganisms, including bacteria, fungi, archaea, viruses, and candidate phyla radiation. A healthy VMB is often characterized by the presence of Lactobacillus species, which play a crucial role in protecting and maintaining homeostasis within the vaginal environment. When this balance is disrupted, the protection of the vaginal epithelium weakens, leading to a reduction in Lactobacillus species and an increased risk of various gynecological and reproductive health issues.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Medicine, McMaster University, Hamilton, ON, Canada.
Introduction: Clinically, a dysbiotic vaginal microbiota (VMB) colonized with anaerobic species such as has been linked to increased susceptibility to viral sexually transmitted infections (STIs) such as Herpes Simplex Virus Type 2 (HSV-2). The mechanism is poorly understood due to the lack of small animal models.
Methods: Mice were inoculated with 10 CFU of the eubiotic bacteria , the dysbiotic bacteria , or PBS as a negative control every 48 h for ten days.
J Sex Med
November 2024
Andrology and Gender Endocrinology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, 50134, Italy.
Background: In males, adenosine (ADO) is known to relax penile smooth muscles, although its role in the vagina is not yet fully elucidated.
Aim: This study investigated the effect of ADO on vagina smooth muscle activity, using a validated female Sprague-Dawley rat model.
Methods: Contractility studies, using noradrenaline-precontracted vaginal strips, tested the effects of ADORA1/3 antagonists and ADORA2A/2B antagonists and agonists.
J Minim Invasive Gynecol
November 2024
Johns Hopkins-Dibley Memorial (Drs. Murdock and Gruber), Washington, DC, USA.
Objective: The objective of this video is to review a case of a patient that presented to urogynecology clinic for prolapse but was noted to have anterior vaginal cyst. In this video, we review differential diagnosis, embryologic origin of vaginal cyst, excision procedure, imaging, and pathology of the vaginal cyst.
Setting: Urogynecology clinic/operating room PARTICIPANT: Patient who presented with anterior vaginal cyst INTERVENTION: Thirty-four-year-old G0 referred to Urogynecology for a vaginal bulge.
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