Blanc SVSE 7 - Blanc - SVSE 7 - Biodiversité, évolution, écologie et agronomie

Integrated multi-approach study of the central mechanisms underlying the hormonal control of female reproductive behaviors – NEUROFEM

Submission summary

Behaviors essential for reproduction by females constitute a chain of behavioral responses beginning with courtship, leading to copulation (lordosis), which in turn ultimately leads to maternal behaviors. Estradiol (E2) plays a key role in the central induction of the ovulatory surge of hormones needed for ovulation and of lordosis behavior. These two responses are conserved in all mammals and are specific to females. Indeed, males are unable to exhibit these responses even when castrated and primed with female hormones. This is due to the fact that testosterone masculinizes and defeminizes the developing male brain during the perinatal period and thus suppresses their ability to express such responses at the adult stage. Very recently, it was shown that E2 can also be involved in the organization of the female brain. E2 acts during the prepubertal period to irreversibly feminize the female sexual behavior. At the adult stage, E2 is needed to maintain and activate transiently female responses.
The molecular mechanisms underlying E2-induced organization and activation of the ovulatory surge of hormones and lordosis behavior still need to be precised. In the central nervous system, E2 activates different signalling pathways involving its nuclear receptors ERa and ERß. First, the relative contribution of each receptor in the central effects of E2 still needs to be defined. Second, the signalling components acting downstream these receptors are not very well known.
In this context, the proposed project aims to:
i) Define the specific roles of ERa and ERß in the central regulation of the ovulatory surge of hormones and expression of female reproductive behaviors.
For this purpose, we will use mice selectively lacking ERa or ERß in the nervous system. In such genetic models, conditional mutation of genes encoding each receptor is restricted to neural cells and does not interfere with their expression in the pituitary, gonad or genital tract where they also play a crucial role in female reproduction. We recently generated, for the first time, mice selectively lacking ERß in the nervous system by using Cre-loxP technology. The conditionnal mouse line for ERa is under generation.
A large characterization will evaluate the impact of each invalidation on female reproduction. The neuroendocrine study will evaluate the onset time of puberty as well as the hormonal status, cyclicity, genital tract morphology and fertility. The behavioral study will include tests of partner choice and olfactory preference, ultrasonic vocalizations, lordosis behavior. Locomotor activity and emotionnal behaviors (anxiety, depression-like behavior), which could interfere with female behaviors, will be also analyzed. The neuro-anatomical study will focus on the organization of brain regions important in the ovulatory surge of hormones and expression of female behaviors.
ii) Identify protein targets acting downstream ERa and ERß by comparing the proteome of control and mutant females. Indeed, if a plethora of factors has been found involved in female responses, the link with ERs needs to be more defined. This study will be performed in hypothalamic areas involved in female reproductive behaviors.

Project coordination

Sakina MHAOUTY KODJA (CNRS-Comportements et Neuroendocrinlogie de la Reproduction) – sakina.mhaouty-kodja@snv.jussieu.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CNRS-CNR CNRS-Comportements et Neuroendocrinlogie de la Reproduction

Help of the ANR 210,000 euros
Beginning and duration of the scientific project: March 2013 - 36 Months

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