Neonatal estrogen exposure results in biphasic age-dependent effects on the skeletal development of male mice

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Abstract

Peak bone mass, one of the most important predictors for fracture risk later in life, is attained during puberty and adolescence and influenced by neonatal and pubertal sex-specific gonadal hormones and GH-IGF-I secretion patterns. This study examined the effects of brief neonatal estrogen (NE) exposure on growth and skeletal development in C57BL/6J mice. A single injection of 100-μg estradiol or vehicle was administered on the first day of life. Growth parameters were monitored and skeletal phenotyping performed at 16 weeks in female mice and at 4 and 16 weeks in male mice. NE exposure negatively impacted adult femoral length in both sexes, but adult body weight, areal bone density, and bone strength in female mice were unaffected. In contrast, somatic growth was attenuated in estrogen-exposed male mice throughout the study period. At the prepubertal time point, theestrogen-exposed males exhibited higher bone mineral density, corticalvolume, and cortical thickness compared with controls. However, by the time of peak bone mass acquisition, the early skeletal findings had reversed; estrogen-exposed mice had lower bone density withreducedcross-sectional area, corticalvolume,andcortical thickness, resulting in corticalbonesthat were less resistant to fracture. NE exposure also resulted in reduced testicular volume and lower circulatingIGF-I.Malemiceexposedtoestrogenonthefirstdayoflifeexperienceage-dependentchanges in skeletal development. Prepubertal animals experience greater endocortical bone acquisition as a result of estrogen exposure. However, by adulthood, continued developmental changes result in overall reduced skeletal integrity

Original languageEnglish (US)
Pages (from-to)193-202
Number of pages10
JournalEndocrinology
Volume156
Issue number1
DOIs
StatePublished - Jan 1 2015

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Estrogens
Bone Density
Bone and Bones
Gonadal Hormones
Puberty
Growth
Thigh
Insulin-Like Growth Factor I
Inbred C57BL Mouse
Growth and Development
Estradiol
Body Weight
Injections

ASJC Scopus subject areas

  • Endocrinology

Cite this

Neonatal estrogen exposure results in biphasic age-dependent effects on the skeletal development of male mice. / Connelly, Kara; Larson, Emily A.; Marks, Daniel; Klein, Robert.

In: Endocrinology, Vol. 156, No. 1, 01.01.2015, p. 193-202.

Research output: Contribution to journalArticle

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