Radovic 2019b MiP2019

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Sava Radovic
Conditional deletion of insulin and IGF1 receptors disturbs transcription of the main markers of mitochondrial biogenesis and architecture/fusion in mouse prepubertal steroidogenic cells of testes but not ovaries.

Link: MiP2019

Radovic SM, Starovlah IM, Capo I, Miljkovic D, Nef S, Kostic TS, Andric SA (2019)

Event: MiP2019

COST Action MitoEAGLE

Controlled changes in mitochondrial biogenesis and morphology are required for cell survival and homeostasis, but the molecular mechanisms are largely unknown. Here, the male and female knock out prepubertal mice (P21), with insulin and IGF1 receptors deletion in steroidogenic tissues (Insr/Igf1r-DKO), were used to investigate transcription of key regulators of mitochondrial biogenesis (Ppargc1a, Ppargc1b, Pparg, Nrf1, Tfam) in Leydig cells, ovaries and adrenals as well as mitochondrial architecture (Mfn1, Mfn2, Opa1) in Leydig cells.

Accordingly, gene expression was followed employing polymerase chain reaction in real time (RQ-PCR), proteins expression detected by western blot, while hormones level was measured by radioimmuno assay.

Results showed that expression of PGC1, the master regulator of mitochondrial biogenesis and integrator of environmental signals, as well as its downstream target Tfam, significantly decreased in testosterone-producing Leydig cells from Insr/Igf1r-DKO animals. This was followed with reduced transcription of Mtnd1, the core subunit of NADH dehydrogenase belonging to the minimal assembly required for catalysis. Transcription of mitochondrial biogenesis markers remained unchanged in ovaries. Differently, in adrenals, the pattern of mitochondrial markers transcripts was the same in both sexes and, besides Pparg and Tfam, opposite from Leydig cells. Number of mitochondria was decreased but their volume and diameter were increased in Leydig cells from Insr/Igf1r-DKO animals. The transcription level of mitochondrial architecture markers (Mfn1, Mfn2) was significantly increased in Leydig cells from Insr/Igf1r-DKO mice suggesting that the mitochondrial architecture and mitochondrial phase of steroidogenesis was affected in males.

Our results are the first to show that insulin and IGF1 receptors are important for mitochondrial biogenesis in gonadal steroidogenic cells of prepubertal males, but not females, as important regulators of both mitochondrial biogenesis and architecture markers transcription.


Bioblast editor: Plangger M, Tindle-Solomon L


Labels: MiParea: mt-Biogenesis;mt-density, Genetic knockout;overexpression, Gender 


Organism: Mouse  Tissue;cell: Genital 





Affiliations and support

Radovic SM(1), Starovlah IM(1), Capo I(2), Miljkovic D(2), Nef S(3), Kostic TS(1), Andric SA(1)
  1. Lab Reproductive Endocrinology Signaling, Lab Chronobiology Aging, Centre Excellence CeRES, Fac Sciences
  2. Dept Histology Embryology, Fac Medicine, Univ Novi Sad, Novi Sad, Serbia
  3. Lab Molecular Developmental Biology Sexual Development, Univ Geneva, Geneva, Switzerland. – sava.radovic@dbe.uns.ac.rs
This work was supported by the grant no. 173057 and grant no. 451-0302807 Centre of Excellence CeRES from the Ministry of Education, Science and Technological Development, Republic of Serbia, grant no. 2130 from the Autonomous Province of Vojvodina as well as grant no. IZ73Z0-128070 from Swiss National Science Foundation.