DOI: 10.5061/dryad.mpg4f4r97
title: Data from: GnRH pulse generator activity in mouse models of polycystic ovary syndrome

description: One in ten women in their reproductive age suffer from polycystic ovary
 syndrome (PCOS) that, alongside subfertility and hyperandrogenism,
 typically presents with increased luteinizing hormone (LH) pulsatility and
 secretion. As such, it is suspected that the arcuate kisspeptin (ARNKISS)
 neurons that represent the GnRH pulse generator are dysfunctional in PCOS.
 We used here in vivo GCaMP fiber photometry and other approaches to
 examine the behavior of the GnRH pulse generator in two mouse models of
 PCOS. We began with the peripubertal androgen (PPA) mouse model of PCOS
 but found that it had a reduction in the frequency of ARNKISS neuron
 synchronization events (SEs) that drive LH pulses. Examining the prenatal
 androgen (PNA) model of PCOS, we observed highly variable patterns of
 pulse generator activity with no significant differences detected in
 ARNKISS neuron SEs, pulsatile LH secretion, or serum testosterone,
 estradiol, and progesterone concentrations. However, an unsupervised
 machine learning approach identified that the ARNKISS neurons of acyclic
 PNA mice continued to exhibit cyclical patterns of activity similar to
 that of normal mice. The frequency of ARNKISS neuron SEs was significantly
 increased in algorithm-identified “diestrous stage” PNA mice compared to
 controls. In addition, ARNKISS neurons exhibited reduced feedback
 suppression to progesterone in PNA mice and their pituitary gonadotrophs
 were also less sensitive to GnRH. These observations demonstrate the
 importance of understanding GnRH pulse generator activity in mouse models
 of PCOS. The unexpected functional disassociation of cyclical GnRH pulse
 generator activity in the acyclic PNA mouse indicates the presence of a
 complex phenotype with deficits at multiple levels of the
 hypothalamo-pituitary-gonadal axis.
description: # eLife-97179-GnRH pulse generator activity in mouse models of polycystic
 ovary syndrome
 [https://doi.org/10.5061/dryad.mpg4f4r97](https://doi.org/10.5061/dryad.mpg4f4r97) ## Description of the data and file structure ### Files and variables #### File: Dryad\_Figure\_Excels-eLife-97179.zip **Description:** We have submitted 10 Excel files in total corresponding to all 10 figures in the paper in (**Dryad_Figure_Excels-eLife-97179.zip**). Each figure has one Excel sheet with panels corresponding to each tab. For example, *file Fig.1-eLife-97179 tab C* corresponds to *Fig.1C* in the original article. More details of data collection and anlysis can be found in figure legends and methods section of the original article here [https://doi.org/10.7554/eLife.97179](https://doi.org/10.7554/eLife.97179.2) **Applicable for all**: * Species of study: mice * Missing values are listed as blank; - Each value represent a mouse (biological replicate); - PPA: peripubertal androgen- treated animals; PNA: prenatal androgen-treated aniamls; control: vehicle for respective groups; - All data are plotted and analysed with Graphpad Prism 10 as described in figure legend and method. **Name: Fig.1-eLife-97179** * Tab C: number of synchronisation events per hour for PPA and controls * Tab D: interval in time between synchronisation events for PPA and controls * Tab E: frequency in % used to plot histogram; bin centers are time in minutes. periP stands for peripubertal androgen- treated animals same as PPA * Tab G: full with half maximum length in seconds for PPA and controls * Tab H: upswing and down swing for PPA and controls in seconds **Name**: **Fig.1Suppl.Fig.1-eLife-97179** * Tab A: body weight of PPA and control animals weeks after capsule implantation * Tab B: time spent in estrous cycle stages in % over 21 days for PPA and controls. **Name:** **Fig.2-eLife-97179** * Tab A: anogenital distance in mm for PNA and control animals * Tab B: body weight in grams for PNA and control animals * Tab C: time spent in estrous cycle stages in % over 21 days for PNA and controls * Tab F: testosterone levels in ng/mL measured by ELISA for PNA and controls * Tab G: androstenedione levels in ng/mL measured by liquid chromatography-mass spectrometry (LC-MS) for PNA and controls * Tab H: estradiol levels in pg/mL measured by LC-MS for PNA and controls * Tab I: progesterone levels in ng/mL measured by LC-MS for PNA and controls **Name:** **Fig.2Suppl.Fig.1-eLife-97179** * Tab A: quantification of mean grey value of kisspeptin immunohistochemistry for PNA and controls in rostral, middle and caudal arcuate nucleus (rARN, mARN, and cARN) * Tab B: quantification of mean grey value of neurokinin B immunohistochemistry for PNA and controls in rostral, middle and caudal arcuate nucleus (rARN, mARN, and cARN) * Tab C: quantification of mean grey value of dynorphin immunohistochemistry for PNA and controls in rostral, middle and caudal arcuate nucleus (rARN, mARN, and cARN) **Name:** **Fig.3-eLife-97179** * Tab E:  number of synchronisation events per hour for PNA and controls * Tab F: interval in time between synchronisation events for PNA and controls * Tab G: frequency in % used to plot histogram; bin centers are time in minutes for PNA and controls * Tab I: full with half maximum length in seconds for PNA and controls * Tab J: upswing and down swing for PNA and controls in seconds **Name:** **Fig.4-eLife-97179** * Tab G: total luteinising hormone (LH) concentration over the bleeding experiment of 4 hours in ng/mL for PNA and controls * Tab H: LH pulse frequency over the bleeding experiment of 4 hours for PNA and controls * Tab J: gonadotropin-releasing hormone (GnRH) triggered LH change measured over -10, 0, 10, 20 minutes around injection for PNA and controls * Tab K: GnRH-evoked changes calculated by LH at 20min minus LH at 0min for PNA and controls **Name: Fig.5-eLife-97179** * Tab B: proportion of each output cluster for PNA and controls  **Name: Fig.6-eLife-97179** * Tab C: number of synchronisation events per hour for PNA and controls * Tab D: interval in time between synchronisation events for PNA and controls * Tab E: frequency in % used to plot histogram; bin centers are time in minutes for PNA and controls **Name: Fig.7-eLife-97179** * Tab E: normalized number of synchronisation events to -3-0 hours with either vehicle or progesterone (P4) injection in controls * Tab F: Tab E: normalized number of synchronisation events to -3-0 hours with either vehicle or progesterone (P4) injection in PNA **Name:Fig.8-eLife-97179** * Tab C: number of synchronisation events per hour for PNA and controls after ovariectomy (OVX) * Tab D: interval in time between synchronisation events for PNA and controls after OVX * Tab E: frequency in % used to plot histogram; bin centers are time in minutes for PNA and controls after OVX * Tab G: full with half maximum length in seconds for PNA and controls after OVX * Tab H: upswing and down swing for PNA and controls in seconds after OVX ## Code/software Excel is needed to view the file.