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Determination of Reproductive Competence by Confirming Pubertal Onset and Performing a Fertility Assay in Mice and Rats
Published on: October 13, 2018
Genetic dissection of puberty in mice
1U. Boehm: Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Kirrberger Straße Building 61.4, 66421 Homburg, Germany. ulrich.boehm@uks.eu.
Experimental Physiology
|August 20, 2013
Summary
Kisspeptin neurons use estrogen receptor alpha to control puberty onset and reproductive cyclicity in female mice. Ablating these neurons early shows developmental compensation, but adult ablation impairs fertility, highlighting their critical role before postnatal day 20.
Area of Science:
- Neuroendocrinology
- Reproductive Biology
- Molecular Endocrinology
Background:
- Gonadotrophin-releasing hormone (GnRH) release is central to vertebrate reproduction.
- Kisspeptin and GPR54 neurons are key modulators of GnRH release and hypothalamic-pituitary-gonadal axis activity.
- The precise role of kisspeptin neurons in pubertal development and reproductive cyclicity requires further elucidation.
Purpose of the Study:
- To investigate the specific roles of kisspeptin neurons and estrogen receptor alpha in regulating GnRH release and pubertal maturation.
- To determine the impact of genetic manipulation and ablation of kisspeptin neurons on reproductive timing and fertility.
- To understand the developmental timeline for the necessity of kisspeptin neurons in reproductive circuitry.
Main Methods:
- Conditional genetic ablation of estrogen receptor alpha in kisspeptin neurons.
- Whole-brain ablation of kisspeptin neurons.
- Generation of female mice lacking kisspeptin receptor GPR54.
- Acute ablation of kisspeptin neurons in adult mice.
- Assessment of puberty onset, ovulatory cyclicity, and fertility.
Main Results:
- Conditional ablation of estrogen receptor alpha in kisspeptin neurons advanced puberty but arrested subsequent maturation and cyclicity.
- Complete ablation of kisspeptin neurons did not affect puberty onset or fertility in females, suggesting developmental compensation.
- Female mice lacking GPR54 neurons were fertile, indicating reproductive maturation without kisspeptin/GPR54 signaling.
- Acute ablation of kisspeptin neurons in adult mice led to inhibited fertility.
- Kisspeptin neurons are essential for reproductive neural circuitry before postnatal day 20.
Conclusions:
- Kisspeptin neurons employ distinct estrogen receptor alpha-dependent "brake" and "accelerator" mechanisms to sequentially regulate GnRH release during pubertal development.
- While kisspeptin signaling is not essential for initial pubertal maturation and fertility due to developmental plasticity, it becomes indispensable for maintaining reproductive function in adults.
- These findings reveal a complex, developmentally regulated role for kisspeptin neurons in the central control of reproduction.
