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Normal reproductive function and fertility rely on the rhythmic secretion of gonadotropin-releasing hormone (GnRH), which is driven by the hypothalamic GnRH pulse generator. A key regulator of the GnRH pulse generator is the posterodorsal subnucleus of the medial amygdala (MePD), a brain region that is involved in processing external environmental cues, including the effect of stress. However, the neuronal pathways enabling the dynamic, stress-triggered modulation of GnRH secretion remain largely unknown. Here, we employ modelling in order to explore the impact of dynamic inputs on GnRH pulse generator activity. We introduce and analyse a mathematical model representing MePD neuronal circuits composed of GABAergic and glutamatergic neuronal populations, integrating it with our GnRH pulse generator model. Our analysis dissects the influence of excitatory and inhibitory MePD projections' outputs on the GnRH pulse generator's activity and reveals a functionally relevant MePD glutamatergic projection to the GnRH pulse generator, which we probe with optogenetics. Our study sheds light on how MePD neuronal dynamics affect the GnRH pulse generator activity and offers insights into stress-related dysregulation.
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http://dx.doi.org/10.1098/rsif.2024.0143 | DOI Listing |
Fertil Steril
August 2025
Division of Reproductive Endocrinology and Infertility, Department Obstetrics and Gynaecology, Erasmus University Medical Center, Wytemaweg 80, 3015CE, Rotterdam, The Netherlands. Electronic address:
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with a prevalence estimated between 10-13%. It is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. Anti-Müllerian hormone (AMH) plays a key role in regulating normal reproductive function in both males and females.
View Article and Find Full Text PDFAnimals (Basel)
August 2025
College of Animal Science and Technology, Shihezi University, Shihezi 832000, China.
The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups ( = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group ( < 0.
View Article and Find Full Text PDFBiol Reprod
August 2025
United States Department of Agriculture (USDA), Agriculture Research Service (ARS), U.S. Meat Animal Research Center, Livestock Bio-systems Research Unit, Clay Center, NE 68933-0165, USA.
Kisspeptin knockout (KISS1-/-) pigs exhibit hypogonadotropic hypogonadism. Hormone analogs targeting different levels of the hypothalamic-pituitary-gonad axis were used to characterize the secretion of reproductive hormones (LH and FSH) and ovarian responses (estradiol and progesterone) in KISS1-/- gilts. Uteri and ovaries were collected from KISS1+/+ and KISS1-/- gilts to confirm ovulatory outcomes.
View Article and Find Full Text PDFElife
July 2025
Harvard Medical School, Boston, United States.
Inactivating mutations in the melanocortin 4 receptor () gene cause monogenic obesity. Interestingly, female patients also display various degrees of reproductive disorders, in line with the subfertile phenotype of Mc4r KO female mice. However, the cellular mechanisms by which MC4R regulates reproduction are unknown.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
August 2025
Department of Human Physiology, University of Oregon, Eugene, Oregon, United States.
Women have a greater reduction in cardiovagal baroreflex sensitivity (CVBRS) as they age which contributes to an elevated cardiovascular disease risk. One potential contributor to the attenuated CVBRS may be reductions in estrogen. Therefore, we tested the hypothesis that isolated estradiol (E) and combined E and progesterone (P) would increase CVBRS to the same extent.
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