title: The Effects of a Single Developmentally Entrained Pulse of Testosterone in Female Neonatal Mice on Reproductive and Metabolic Functions in Adult Life.
abstract: Early postnatal exposures to sex steroids have been well recognized to modulate predisposition to diseases of adulthood. There is a complex interplay between timing, duration and dose of endocrine exposures through environmental or dietary sources that may alter the sensitivity of target tissues to the exogenous stimuli. In this study, we determined the metabolic and reproductive programming effects of a single developmentally entrained pulse of testosterone (T) given to female mice in early postnatal period. CD-1 female mice pups were injected with either 5 μg of T enanthate (TE) or vehicle (control [CON] group) within 24 hours after birth and followed to adult age. A total of 66% of T-treated mice exhibited irregular cycling, anovulatory phenotype, and significantly higher ovarian weights than vehicle-treated mice. Longitudinal nuclear magnetic resonance measurements revealed that TE group had greater body weight, whole-body lean, and fat mass than the CON group. Adipose tissue cellularity analysis in TE group revealed a trend toward higher size and number than their littermate CONs. The brown adipose tissue of TE mice exhibited white fat infiltration with down-regulation of several markers, including uncoupling protein 1 (UCP-1), cell death-inducing DNA fragmentation factor, α-subunit-like effector A, bone morphogenetic protein 7 as well as brown adipose tissue differentiation-related transcription regulators. T-injected mice were also more insulin resistant than CON mice. These reproductive and metabolic reprogramming effects were not observed in animals exposed to TE at 3 and 6 weeks of age. Collectively, these data suggest that sustained reproductive and metabolic alterations may result in female mice from a transient exposure to T during a narrow postnatal developmental window.
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Hyeran
authors.initials: H
authors.lastname: Jang
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Tyler
authors.initials: T
authors.lastname: Guarneri
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Carlo
authors.initials: C
authors.lastname: Serra
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Mary
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fried
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Karol
authors.initials: K
authors.lastname: Pencina
authors.affiliation: Research Program in Men's Health: Aging and Metabolism (H.J., S.B., T.G., C.S., W.G., K.P., R.J.), Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Boston Nutrition and Obesity Research Center (M.S., M.-J.L., S.K.F.), Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Ravi
authors.initials: R
authors.lastname: Jasuja
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008660:Metabolism / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000254:growth & development; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D013997:Time Factors; D000071256:Uncoupling Protein 1
chemical_list: D055419:Bone Morphogenetic Protein 7; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D013739:Testosterone; D004958:Estradiol; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone