Steroidogenic factor 1 (SF-1), officially designated NR5A1, is essential for gonadal and adrenal development and for the normal structure of the ventromedial hypothalamus, as demonstrated by SF-1 knockout mice (SF-1 KO), but much less is known about the possible effects of haploinsufficiency of the SF-1 gene. In the present study, maternal behavior in SF-1 KO heterozygous mice was evaluated. Behavioral tests revealed that SF-1 KO heterozygous females have impaired maternal behavior. In comparison to WT females, SF-1 KO heterozygous females retrieved significantly fewer pups into their nests, latency to retrieve and crouch over the pups was longer, and their nests were lower quality. As suggested by previous studies full dosage of SF-1 gene is needed for appropriate stress response and expression of BDNF in the brain, and this might present a mechanism through which maternal behavior in SF-1 KO heterozygous females is impaired.
COBISS.SI-ID: 4164474
The molecular mechanisms underlying spleen development and those implicated in congenital asplenia, a condition associated with overwhelming infections remain largely unknown. During spleen organogenesis, the transcription factor TLX1 controls cell fate specification and organ expansion, and loss of it causes asplenia in mice. In humans, deregulation of TLX1 expression has been recently proposed as a mechanism underling the pathogenesis of congenital asplenia in patients carrying mutations of the transcription factor SF-1. Herein, we demonstrate that loss of Tlx1 during formation of the splenic anlage causes increased retinoic acid (RA) signaling. We show that an excess or deficiency in retinoids, as observed in Cyp26b1 or Rdh10 mutants respectively, result in spleen growth arrest. Uncontrolled RA activity consequently to Tlx1 loss causes premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling partially rescues the spleen defect. These findings establish the critical role of TLX1 in controlling RA metabolism, and provide novel mechanistic insights into the molecular determinants underlying human congenital asplenia.
COBISS.SI-ID: 4158330
Kisspeptin, a regulator of reproductive function and puberty in mammals, is expressed in the rostral periventricular nucleus (AVPV) and arcuate nucleus (Arc) and its expression is at least partially regulated by estradiol in rodents. The aim of the present study was to determine contributions of genetic factors and gonadal steroid hormones in the sexual differentiation of kisspeptin immunoreactive cell populations in the AVPV and Arc during postnatal development using agonadal Steroidogenic factor-1 knockout (SF-1 KO) mice. To examine effects of gonadal hormones on pubertal development of kisspeptin neurons, SF-1 KO mice were treated with estradiol benzoate (EB) from P25 to P36 and their brains examined at P36. No sex differences were observed in SF-1 KO mice during postnatal development and after treatment with EB, which failed to increase the number of kisspeptin- ir cells at P36 in SF-1 KO mice to the levels found in WT control females. This suggests that specific time periods of estradiol actions or other factors are needed for sexual differentiation of the pattern of immunoreactive kisspeptin in the AVPV. Kisspeptin immunoreactivity in the Arc was significantly higher in gonadally intact WT and SF-1 KO females than male mice at P36 during puberty. Further, in WT and SF-1 KO females, but not in males, adult levels were reached at P36. This suggests that maturation of the kisspeptin system in the Arc differs between sexes and is regulated by gonad- independent mechanisms.
COBISS.SI-ID: 4009594