Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism.

Isabel Bar��n-Mendoza, M��nica Mart��nez-Marcial, Marcos Garc��a-Ju��rez, Montserrat Mej��a-Hern��ndez, Yesenia Cort��s-S��nchez, Carmen J Zamora-S��nchez, Jorge Omar Garc��a-Rebollar, Roberto Chavira-Ram��rez, David Ordaz-Rosado, Ignacio Camacho-Arroyo, Miriam Betzabe Tecamachalzi-Silvar��n, Omar Montes-Narv��ez, Oscar Gonz��lez-Flores, Roc��o Garc��a-Becerra, Aliesha Gonz��lez-Arenas
Author Information
  1. Isabel Bar��n-Mendoza: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, Ciudad de M��xico, M��xico.
  2. M��nica Mart��nez-Marcial: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, Ciudad de M��xico, M��xico.
  3. Marcos Garc��a-Ju��rez: Centro de Investigaci��n en Reproducci��n Animal, Universidad Aut��noma de Tlaxcala-CINVESTAV, Tlaxcala, M��xico.
  4. Montserrat Mej��a-Hern��ndez: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, Ciudad de M��xico, M��xico.
  5. Yesenia Cort��s-S��nchez: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, Ciudad de M��xico, M��xico.
  6. Carmen J Zamora-S��nchez: Unidad de Investigaci��n en Reproducci��n Humana, Instituto Nacional de Perinatolog��a-Facultad de Qu��mica, Universidad Nacional Aut��noma de M��xico, M��xico.
  7. Jorge Omar Garc��a-Rebollar: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, Ciudad de M��xico, M��xico.
  8. Roberto Chavira-Ram��rez: Departamento de Biolog��a de la Reproducci��n Dr. Carlos Gual Castro, Instituto Nacional de Ciencias M��dicas y Nutrici��n Salvador Zubir��n, 14080 Ciudad de M��xico, M��xico.
  9. David Ordaz-Rosado: Departamento de Biolog��a de la Reproducci��n Dr. Carlos Gual Castro, Instituto Nacional de Ciencias M��dicas y Nutrici��n Salvador Zubir��n, 14080 Ciudad de M��xico, M��xico.
  10. Ignacio Camacho-Arroyo: Unidad de Investigaci��n en Reproducci��n Humana, Instituto Nacional de Perinatolog��a-Facultad de Qu��mica, Universidad Nacional Aut��noma de M��xico, M��xico.
  11. Miriam Betzabe Tecamachalzi-Silvar��n: Facultad de Ciencias para el Desarrollo Humano, Universidad Aut��noma de Tlaxcala, M��xico.
  12. Omar Montes-Narv��ez: Centro de Investigaci��n en Reproducci��n Animal, Universidad Aut��noma de Tlaxcala-CINVESTAV, Tlaxcala, M��xico.
  13. Oscar Gonz��lez-Flores: Centro de Investigaci��n en Reproducci��n Animal, Universidad Aut��noma de Tlaxcala-CINVESTAV, Tlaxcala, M��xico.
  14. Roc��o Garc��a-Becerra: Departamento de Biolog��a Molecular y Biotecnolog��a, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, Ciudad de M��xico, M��xico.
  15. Aliesha Gonz��lez-Arenas: Departamento de Medicina Gen��mica y Toxicolog��a Ambiental, Instituto de Investigaciones Biom��dicas, Universidad Nacional Aut��noma de M��xico, Ciudad de M��xico, M��xico. Electronic address: alieshag@iibiomedicas.unam.mx.

Abstract

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain. Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.

Keywords

MeSH Term

Animals
Female
Mice
Hypothalamus
Disease Models, Animal
Mice, Inbred C57BL
Estrous Cycle
Reproductive Health
Autistic Disorder
Autism Spectrum Disorder
Reproduction
Progesterone
Estradiol
Male
Gonadal Steroid Hormones

Chemicals

Progesterone
Estradiol
Gonadal Steroid Hormones

Word Cloud

Created with Highcharts 10.0.0reproductiveC58/JfemalesautismASDaxisstrainhormonalcycleAutismHPOhealthmodelmouseperformanceprofilescomparedcontrolfindingsestrousmicealsoreceptorcontentSpectrumDisordercharacterizeddifferencessocialcommunicationinteractionwellareasfocusedinterestsand/orrepetitivebehaviorsRecentstudieshighlightedhigherprevalenceendocrinedisturbancesamongspectrumhintingpotentialdisruptionswithinhypothalamus-pituitary-ovaryresearchaimsexploredisparitiesusinganimalinbredfocusC57BL/6JrevealeddisruptedevidencedlowerfrequencycompletecycleslackcyclicalreleaseestradiolprogesteroneexhibitedpoorseveralparametersincludinglifespanfertilityindexFurthermoreestrogenalphashowedmarkeddecreasehypothalamusalterationsimbalancesreducedfunctionimplydysregulationAdditionallyin-silicostudyidentifiedgroupgenesinvolvedinfertilitycarryingsingle-nucleotidepolymorphismsSNPshumanorthologsassociatedoffervaluableinsightsmolecularunderpinningsneuroendocrinedisruptionissuesobservedDisruptionssexhypothalamichormonereceptorsEstradiolEstrogenEstrousHypothalamusMouseProgesteroneReproduction

Similar Articles

Cited By