Avaliação da maturação sexual e parâmetros reprodutivos em camundongos machos com hipopituitarismo congênito
Tipo
TCC
Data de publicação
2024-12
Periódico
Citações (Scopus)
Autores
Chishman, Julia Matias
Orientador
Camargo, Esther Lopes Ricci Adari
Carvalho, Luciani Renata Silveira de
Carvalho, Luciani Renata Silveira de
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Introdução: A glândula hipofisária desempenha um papel essencial na produção e
secreção hormonal, dependendo de fatores de transcrição para sua formação
embrionária. Entre esses fatores está o gene Prop1, responsável pela diferenciação
terminal das linhagens hipofisárias produtoras de hormônios. Alterações no Prop1
estão associadas ao hipopituitarismo congênito, condição que compromete
crescimento, desenvolvimento sexual e reprodutivo. Embora a linhagem Ames tenha
sido inicialmente considerada infértil, tratamentos com levotiroxina e GH restauraram
a fertilidade e permitiram a observação de maturação sexual espontânea. Objetivo:
Caracterizar a prevalência do fenômeno de maturação sexual espontânea em
camundongos machos pertencentes a linhagem Ames mantidos na FMUSP.
Materiais e Métodos: Camundongos normais e mutantes da linhagem Ames, com
mutação no gene Prop1, foram monitorados a partir dos 21 dias para sinais de
maturação sexual, como descida testicular e abertura prepucial. Análises histológicas
testiculares foram realizadas para avaliar túbulos seminíferos e presença de células
germinativas maduras. Resultados: Os camundongos mutantes apresentaram
maturação sexual espontânea tardia em relação aos controles. Enquanto os controles
alcançaram a maturidade aos 25 ± 2,49 dias, os mutantes demoraram até 60 ± 11,70
dias (p = 0,0002). O peso médio no momento da maturação também foi
significativamente menor nos mutantes (6,33 ± 0,31 g) comparado aos controles
(12,02 ± 0,73 g, p < 0,0001). Aos 90 dias, os mutantes mantiveram menor peso
corporal (6,88 ± 0,59 g vs. 23,58 ± 0,89 g) e comprimento naso-anal (5,7 ± 0,53 cm
vs. 7,7 ± 0,53 cm, p = 0,0098). A análise histológica revelou túbulos seminíferos
desorganizados nos mutantes, com escores de Johnsen significativamente mais
baixos (6,07 ± 0,42 e 9,33 ± 0,27, p = 0,0009). A análise dos túbulos seminíferos
indicam estágios variados de desenvolvimento nos Mutantes. Apesar dessas
alterações, todos os mutantes alcançaram maturação sexual completa. Conclusão:
Camundongos mutantes apresentaram atraso na maturação sexual, diferenças
corporais e reprodutivas, e espermatogênese heterogênea. Apesar de alterações nos
túbulos seminíferos e desenvolvimento testicular, todos atingiram maturação
completa.
Introduction: The pituitary gland plays a crucial role in hormonal production and secretion, relying on transcription factors for its embryonic development. Among these is the Prop1 gene, essential for the terminal differentiation of hormone-producing pituitary lineages. Prop1 mutations are associated with congenital hypopituitarism, a condition that impairs growth, sexual, and reproductive development. Although the Ames lineage was initially considered infertile, treatments with levothyroxine and GH restored fertility and allowed observation of spontaneous sexual maturation. Objective: To characterize the prevalence of spontaneous sexual maturation in male Ames mice maintained at FMUSP. Materials and Methods: Normal and Ames mutant mice with a Prop1 gene mutation were monitored from 21 days of age for signs of sexual maturation, such as testicular descent and preputial opening. Testicular histological analyses were performed to evaluate seminiferous tubules and the presence of mature germ cells. Results: Mutant mice exhibited delayed spontaneous sexual maturation compared to controls. While controls matured at 25 ± 2.49 days, mutants required up to 60 ± 11.70 days (p = 0.0002). Mean weight at maturation was significantly lower in mutants (6.33 ± 0.31 g) compared to controls (12.02 ± 0.73 g, p < 0.0001). At 90 days, mutants maintained lower body weight (6.88 ± 0.59 g vs. 23.58 ± 0.89 g) and naso-anal length (5.7 ± 0.53 cm vs. 7.7 ± 0.53 cm, p = 0.0098). Histological analysis revealed disorganized seminiferous tubules in mutants, with significantly lower Johnsen scores (6.07 ± 0.42 vs. 9.33 ± 0.27, p = 0.0009). Seminiferous tubule analysis indicated varied developmental stages in mutants. Despite these alterations, all mutants achieved complete sexual maturation. Conclusion: Mutant mice exhibited delayed sexual maturation, along with differences in body and reproductive characteristics and heterogeneous spermatogenesis. Despite alterations in seminiferous tubules and testicular development, all mutants achieved complete maturation.
Introduction: The pituitary gland plays a crucial role in hormonal production and secretion, relying on transcription factors for its embryonic development. Among these is the Prop1 gene, essential for the terminal differentiation of hormone-producing pituitary lineages. Prop1 mutations are associated with congenital hypopituitarism, a condition that impairs growth, sexual, and reproductive development. Although the Ames lineage was initially considered infertile, treatments with levothyroxine and GH restored fertility and allowed observation of spontaneous sexual maturation. Objective: To characterize the prevalence of spontaneous sexual maturation in male Ames mice maintained at FMUSP. Materials and Methods: Normal and Ames mutant mice with a Prop1 gene mutation were monitored from 21 days of age for signs of sexual maturation, such as testicular descent and preputial opening. Testicular histological analyses were performed to evaluate seminiferous tubules and the presence of mature germ cells. Results: Mutant mice exhibited delayed spontaneous sexual maturation compared to controls. While controls matured at 25 ± 2.49 days, mutants required up to 60 ± 11.70 days (p = 0.0002). Mean weight at maturation was significantly lower in mutants (6.33 ± 0.31 g) compared to controls (12.02 ± 0.73 g, p < 0.0001). At 90 days, mutants maintained lower body weight (6.88 ± 0.59 g vs. 23.58 ± 0.89 g) and naso-anal length (5.7 ± 0.53 cm vs. 7.7 ± 0.53 cm, p = 0.0098). Histological analysis revealed disorganized seminiferous tubules in mutants, with significantly lower Johnsen scores (6.07 ± 0.42 vs. 9.33 ± 0.27, p = 0.0009). Seminiferous tubule analysis indicated varied developmental stages in mutants. Despite these alterations, all mutants achieved complete sexual maturation. Conclusion: Mutant mice exhibited delayed sexual maturation, along with differences in body and reproductive characteristics and heterogeneous spermatogenesis. Despite alterations in seminiferous tubules and testicular development, all mutants achieved complete maturation.
Descrição
Palavras-chave
Maturação sexual , Hipopituitarismo Congênito , Epigenética , Sexual maturation , Congenital Hypopituitarism , Epigenetics