Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts.

CONTEXT: Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. AIMS: The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. METHODS: The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). KEY RESULTS: The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. CONCLUSIONS: These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. IMPLICATIONS: These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development.

Object and food novelty induce distinct patterns of c-fos immunoreactivity in amygdala and striatum in domestic male chicks (Gallus gallus domesticus).

Avoidance of novelty, termed neophobia, protects animals from potential dangers but can also impair their adaptation to novel environments or food resources. This behaviour is particularly well described in birds but the neurobiological correlates remain unexplored. Here, we measured neuronal activity in the amygdala and the striatum, two brain regions believed to be involved in novelty detection, by labelling the early gene c-fos following chicks exposure to a novel food (NF), a novel object (NO) or a familiar food (FF). NF and NO chicks showed significantly longer latencies to touch the food, less time eating and emitted more fear-vocalizations than control chicks. Latency to touch the food was also longer for NO than for NF chicks. Significantly higher densities of c-fos positive cells were present in all the nuclei of the arcopallium/amygdala of NF and NO chicks compared to FF chicks. Also, NO chicks showed higher positive cell densities than NF chicks in the posterior amygdaloid, the intermediate and the medial arcopallium. Exposure to novel food or object induced a similar increase in c-fos expression in the nucleus accumbens and the medial striatum. Our data provide evidence activation of the arcopallium/amygdala is specific of the type of novelty. The activation of striatum may be more related to novelty seeking.

Brain mapping of the gonadotropin-inhibitory hormone-related peptide 2 with a novel antibody suggests a connection with emotional reactivity in the Japanese quail (Coturnix japonica, Temminck & Schlegel, 1849).

Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide first discovered in the quail brain that is involved in the control of reproductive physiology and behaviors, and stress response. GnIH gene encodes a second peptide, GnIH-related peptide-2 (RP2), the distribution and function of which remain unknown. We therefore studied GnIH-RP2 distribution by immunohistochemistry using a novel antibody capable of discriminating between GnIH and GnIH-RP2. The overall distribution of GnIH-RP2 is similar to that of GnIH. The vast majority of labeled neurons is located in the paraventricular nucleus (PVN) of the hypothalamus. Labeling of fibers is conspicuous in the diencephalon, but present also in the mesencephalon and telencephalon. Several regions involved in the control of reproduction and stress response (the PVN, septum, bed nucleus of the stria terminalis and nucleus commissura pallii) showed a dense network of immunolabeled fibers. To investigate the potential function of GnIH-RP2 we compared its expression in two quail lines genetically selected for divergence in their emotional reactivity. A quantitative analysis in the above-mentioned brain regions showed that the density of fibers was similar in the two lines. However, the number of GnIH-RP2 labeled neurons was higher in the median portion of the PVN in birds with higher emotional reactivity. These results point to a possible involvement of GnRH-RP2 in modulating stress response and/or emotional reactivity.

Yolk hormones influence in ovo chemosensory learning, growth, and feeding behavior in domestic chicks.

In this study, we assessed whether prenatal exposure to elevated yolk steroid hormones can influence in ovo chemosensory learning and the behavior of domestic chicks. We simulated a maternal environmental challenge by experimentally enhancing yolk progesterone, testosterone, and estradiol concentrations in hen eggs prior to incubation. The embryos from these hormones-treated eggs (HO) as well as sham embryos (O) that had received the vehicle-only were exposed to the odor of fish oil (menhaden) between embryonic Days 11 and 20. An additional group of control embryos (C) was not exposed to the odor. All chicks were tested following hatching for their feeding preferences between foods that were or were not odorized with the menhaden odor. In the 3-min choice tests, the behavior of O chicks differed significantly according to the type of food whereas C and HO chicks showed no preference between odorized and non-odorized food. Our result suggests weaker response in HO chicks. In addition, HO chicks showed impaired growth and reduced intake of an unfamiliar food on the 24-h time scale compared to controls. Our data suggest that embryonic exposure to increased yolk hormone levels can alter growth, chemosensory learning, and the development of feeding behaviors.

Development of social familiarity in ewes.

We assessed the development of individual discrimination resulting from direct contact/familiarization in ewes. Unfamiliar ewes were introduced during 6, 24 or 72 h in groups of already familiarized ewes. At the end of this contact period, the development of social recognition with the animal that has been introduced was assessed using two different types of tests: a Y-maze preference test and a delayed paired close encounters test where tested ewes are successively and randomly interacting with the familiar animal and an unfamiliar conspecific. The results of both tests showed that ewes developed a recognition of the familiar animal in comparison to a completely unfamiliar female. However, this preference was evidenced after 24 h of contact when using the paired close encounters test whereas it appears only after 72 h when using the Y-maze test, suggesting that the paired close encounters test is a more sensitive methodology to assess the development of social familiarization. The importance of estrogens, in the formation of social familiarization was also evaluated. To this end, social recognition in the paired close encounters test was compared between ovariectomized animals receiving estrogen implants or not. Despite significant high levels of estradiol in estrogen implanted females, no major differences in recognition appeared between groups, suggesting that in our conditions estrogens do not have major influence on social familiarization.