Effects of estrogen deficiency during puberty on maxillary and mandibular growth and associated gene expression \u2013 an \u03bcCT study on rats

Erika Calvano Küchler,Moritz Blanck-Lubarsch,Maria Bernadete Sasso Stuani,Christian Kirschneck,Guido Marañón-Vásquez,Peter Proff,Marjorie Ayumi Omori,Rafaela Mariana De Lara,Agnes Schroeder,Paulo Nelson-Filho,Flares Baratto-Filho

doi:10.1186/s13005-021-00265-3

Erika Calvano Küchler, Moritz Blanck-Lubarsch + Show 9 more

Open Access

https://doi.org/10.1186/s13005-021-00265-3

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Abstract

BackgroundEstrogen is a well-known and important hormone involved in skeletal homeostasis, which regulates genes involved in bone biology. Some studies support that estrogen is important for craniofacial growth and development. Therefore this in vivo animal study aimed to investigate, whether and in which way low estrogen levels in the prepubertal period affect craniofacial development in the postpubertal stage and to quantify the gene expression of RANK, RANKL and OPG in cranial growth sites in ovariectomized estrogen-deficient rats during puberty.MethodsControl (sham-operated, n = 18) and ovariectomy (OVX, n = 18) surgeries were performed on 21-days-old female Wistar rats. Animals euthanized at an age of 45 days (pubertal stage) were used for gene expression analyses (n = 6 per group) and immunohistochemistry of RANK, RANKL and OPG. Animals euthanized at 63 days of age (post-pubertal stage) were used for craniofacial two-dimensional and three-dimensional craniofacial measurements using μCT imaging (n = 12 per group).ResultsIn the μCT analysis of the mandible and maxilla many statistically significant differences between sham-operated and OVX groups were observed, such as increased maxillary and mandibular bone length in OVX animals (p < 0.05). Condylar volume was also significantly different between groups (p < 0.05). The sham-operated group showed a higher level of RANK expression in the midpalatal suture (p = 0.036) and the RANKL:OPG ratio levels were higher in the OVX group (p = 0.015).ConclusionsOur results suggest that estrogen deficiency during the prepubertal period is associated with alterations in the maxillary and mandibular bone length and condylar growth.

Highlights

Estrogen is a well-known and important hormone involved in skeletal homeostasis, which regulates genes involved in bone biology
Estrogen is an important hormone involved in the skeletal homeostasis that regulates different aspects of bone metabolism, development, modeling and remodeling
If estrogen deficiency affects craniofacial growth via the Receptor activator of nuclear factor-κB (RANK), Receptor Activator of NF-κB Ligand (RANKL) and OPG axis by investigating their expression at growth sites of both maxilla and mandible during puberty and estrogen deficiency

Summary

Introduction

Estrogen is a well-known and important hormone involved in skeletal homeostasis, which regulates genes involved in bone biology. Some studies support that estrogen is important for craniofacial growth and development. This in vivo animal study aimed to investigate, whether and in which way low estrogen levels in the prepubertal period affect craniofacial development in the postpubertal stage and to quantify the gene expression of RANK, RANKL and OPG in cranial growth sites in ovariectomized estrogen-deficient rats during puberty. Estrogen is an important hormone involved in the skeletal homeostasis that regulates different aspects of bone metabolism, development, modeling and remodeling. There is an increase in estrogen levels leading to the development of secondary sexual characteristics and a significant increase in growth rate [2]. It is well known that estrogen deficiency can cause osteoporosis [12, 13], decrease mineral density in bones and delay the epiphyseal maturation [14]

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