Data from: Kisspeptin made in the preoptic area is required for normal estradiol-induced LH surges and optimal fertility in females.
Data files
May 14, 2026 version files 34.04 KB
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Dryad_All_figures_data_for_THCreKF_study.xlsx
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README.md
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Abstract
Ovulation is triggered by a surge in luteinizing hormone (LH) secretion from the pituitary. The LH surge is itself driven by a surge in GnRH release induced by estrogen positive feedback action in the hypothalamus. While ERα-expressing kisspeptin (Kiss1) neurons in the preoptic area (in mice, the rostral periventricular region of the third ventricle [RP3V]) are proposed to mediate this estrogen positive feedback event, the functional necessity of RP3V-derived kisspeptin for the LH surge has not been directly tested. Here we leveraged Cre/lox technology and the known high co-expression of tyrosine hydroxylase (TH) with Kiss1 in only the RP3V region to generate novel transgenic mice with selective knockout (KO) of the Kiss1 gene in just RP3V neurons (Kiss1RP3V KO mice). In situ hybridization confirmed a significant 70% reduction in cells expressing Kiss1 in the RP3V region, but not in the arcuate nucleus, along with no change in RP3V Th expression. Kiss1RP3V KO females exhibited normal pubertal timing and estrous cycles. However, functional interrogation of the ability of Kiss1RP3V KO females to generate an estradiol-induced LH surge demonstrated markedly blunted LH surges and reduced occurrence of surges, in line with the partial Kiss1RP3V knockout in this group. Correspondingly, fertility assessment revealed significant subfertility, including fewer and smaller litters. This subfertility is consistent with the observed impaired LH surges, though the downstream ovarian mechanism(s) underlying the smaller litters still needs to be determined. These findings provide direct causal evidence that RP3V-derived kisspeptin is essential for normal LH surge magnitude and optimal fertility.
Dataset DOI: 10.5061/dryad.zpc866tph
General information
1. Title of Dataset: “Data from: Kisspeptin made in the preoptic area is required for normal estradiol-induced LH surges and optimal fertility in females”
2. Contact Author Information: Dr. Alexander S. Kauffman, Department of OBGYN and Reproductive Sciences, University of California San Diego, 9500 Gilman Drive, #0674, La Jolla, California 92093. email: akauffman@ucsd.edu
3. Corresponding Publication: The manuscript containing this data has been peer-reviewed and accepted for publication: M Puffer, J Yang, LA Esparza, L Rose, V Duong, S Radovick, and AS Kauffman. Kisspeptin made in the preoptic area is required for normal estradiol-induced LH surges and optimal fertility in females. Endocrinology, 2026.
Description of the data and file structure
The data are from a study that compared reproductive hormone levels, puberty onset, body weights, fertility measures, and hypothalamic neuron counts in female transgenic mice that were lacking Kiss1 gene expression in the RP3V brain region or control female mice, as described in detail in the Methods section of the published manuscript (M Puffer, J Yang, LA Esparza, L Rose, V Duong, S Radovick, and AS Kauffman. Kisspeptin made in the preoptic area is required for normal estradiol-induced LH surges and optimal fertility in females. Endocrinology, 2026).
Files and variables
File: Dryad_All_figures_data_for_THCreKF_study.xlsx
Data File Description: The dataset used to generate all graphs in the figures for the associated manuscript are deposited here in an .xlsx file "Dryad_All_figures_data_for_THCreKF_study.xlsx". The .xlsx file comprises 8 separate worksheets named with the corresponding manuscript Figure number (e.g., Fig 1, Fig 3A, Fig 3C-E, Fig 4, etc.) which indicates which specific figure or figure panels the data are presented in the published manuscript, along with a short identifying text in the worksheet name (e.g. Kiss1 cells, female puberty, basal LH, body weights, etc.) which gives additional context about what the data in that worksheet corresponds to. Blank cells indicate no value for that measure for that animal.
All methods and analyses are described in detail in the published manuscript Methods section.
Abbreviations:
- RP3V, rostral periventricular nucleus of the 3rd ventricle, a region in the hypothalamus
- ARC, arcuate nucleus of the hypothalamus
- PND, postnatal day (age after birth)
- LH, luteinizing hormone
- BW, body weight
- g, grams
- ng/ml, nanograms per milliliter
- VO, vaginal opening (day of; an early stage pubertal marker)
- FE, first estrus (day of; a late stage pubertal marker)
- AM, morning period
- PM, evening period
- Cre-, mice lacking Cre recombinase expression in kisspeptin neurons
- Cre+, mice expressing Cre recombinase in kisspeptin neurons
- TH, tyrosine hydroxylase
- CON, control mice
- cKO, conditional KO mice in which Kiss1 gene was conditionally deleted in TH cells (in RP3V brain area) using Cre/lox technology
Treatment Groups:
- CON, control mice (Cre-/fl fl, termed “CON” in the manuscript)
- cKO, experimental mice (Cre+/fl fl; termed “Kiss1RP3V KO” in the manuscript) in which Kiss1 gene is selectively deleted in TH cells (in RP3V brain area)
Variables Analyzed (and units) for corresponding Figure in the manuscript
Figures 1C, E: Kiss1 cells (number of).
These data are the mean number of Kiss1-expressing cells per brain slice detected in either the RP3V or ARC brain regions of adult cKO and CON female mice, as detected with BaseScope in situ hybridization.
Figures 2: TH cells (number of).
These data are the mean number of TH-expressing cells per brain slice detected in the RP3V brain region of adult cKO and CON female mice, as detected with RNAscope in situ hybridization.
Figure 3A: Body weight (g).
These data are the mean body weights (BW; measured in g) of either cKO and CON female mice at different postnatal ages, starting at postnatal day 21 and ending at postnatal day 45.
Figure 3B-F: Vaginal Opening (day of), First Estrus (day of), Body weight (g).
These data are pubertal measures in female cKO and CON mice. VO (day of) is graphed in Fig 3B, C, and mean BW on the day of VO (g) is graphed in Fig 3D. FE (day of) is graphed in Fig. 3E, F.
Figure 4: Estrous cycle length (days), % time in each cycle stage (%).
These data are the female estrous cycles in adult cKO and CON mice. Mean estrous cycle length (in days) is in Fig 4C. Fig 4D presents mean % time females in each group spent in each of the 3 cycle stages (diestrus, proestrus, estrus).
Figure 5: Luteinizing hormone (LH) levels in the blood (ng/ml blood serum) in adult mice.
These data are the basal blood serum levels of LH (measured in ng LH/ml blood serum) of either cKO and CON adult female mice in diestrus.
Figure 6: Luteinizing hormone surge (LH) secretion (ng LH/ml blood).
These data are LH surge secretion of adult cKO and CON female mice. Figure 6A depicts blood LH levels (ng/ml) in cKO and CON females at either the AM or PM time-points. Fig 6B is the % of females in each group demonstrating PM LH levels above the LH surge threshold of 0.75 ng/ml. Figure 6C depicts blood LH levels (ng/ml) in cKO and CON females at the PM time-point for only the mice in each group whose LH surpassed the LH surge threshold of 0.75 ng/ml.
Figure 7: Number of days until 1st litter (days), number of litters, total number of pups born in 12 weeks, and number of pups per litter.
These data are fertility measures in adult female cKO and CON mice paired with a CON male for 12 weeks. Fig 7A is the mean number of days until the 1st litter was born (days), Fig 7B is the mean number of litters born in 12 weeks, Fig 7C is the mean number of pups per litter, and Fig 7D is the mean total number of pups born in 12 weeks.