Related Experiment Video

Updated: Aug 23, 2025

Methods for Studying Uterine Contributions to Pregnancy Establishment in an Ovariectomized Mouse Model

Methods for Studying Uterine Contributions to Pregnancy Establishment in an Ovariectomized Mouse Model

Published on: April 7, 2023

Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer

Shannon D'Urso¹, Pooja Arumugam², Therese Weider^3,4

¹Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.

|November 2, 2022

Abstract

Background:

Observational epidemiological studies suggest a link between several factors related to ovulation and reproductive function and endometrial cancer (EC) risk; however, it is not clear whether these relationships are causal, and whether the risk factors act independently of each other. The aim of this study was to investigate putative causal relationships between the number of live births, age at last live birth, and years ovulating and EC risk. METHODS: We conducted a series of observational analyses to investigate various risk factors and EC risk in the UK Biobank (UKBB). Additionally, multivariate analysis was performed to elucidate the relationship between the number of live births, age at last live birth, and years ovulating and other related factors such as age at natural menopause, age at menarche, and body mass index (BMI). Secondly, we used Mendelian randomization (MR) to assess if these observed relationships were causal. Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of woman's number of live births, age at menopause and menarche, and BMI. We conducted a genome-wide association analysis using the UKBB to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

Results:

We found evidence for a causal effect of the number of live births (inverse variance weighted (IVW) odds ratio (OR): 0.537, p = 0.006), the number of years ovulating (IVW OR: 1.051, p = 0.014), in addition to the known risk factors BMI, age at menarche, and age at menopause on EC risk in the univariate MR analyses. Due to the close relationships between these factors, we followed up with multivariable MR (MVMR) analysis. Results from the MVMR analysis showed that number of live births had a causal effect on EC risk (OR: 0.783, p = 0.036) independent of BMI, age at menarche and age at menopause.

Conclusions:

MVMR analysis showed that the number of live births causally reduced the risk of EC.

Keywords:

Age at last live birth Endometrial cancer Fertility GWAS Mendelian randomization Number of live births UK biobank Years ovulating

More Related Videos

Analysis of Chromosome Segregation, Histone Acetylation, and Spindle Morphology in Horse Oocytes

Analysis of Chromosome Segregation, Histone Acetylation, and Spindle Morphology in Horse Oocytes

Published on: May 11, 2017

Characterization and Functional Prediction of Bacteria in Ovarian Tissues

Characterization and Functional Prediction of Bacteria in Ovarian Tissues

Published on: October 23, 2021

Related Concept Videos

Oogenesis

Oogenesis

In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...

Randomized Experiments

Randomized Experiments

The randomization process involves assigning study participants randomly to experimental or control groups based on their probability of being equally assigned. Randomization is meant to eliminate selection bias and balance known and unknown confounding factors so that the control group is similar to the treatment group as much as possible. A computer program and a random number generator can be used to assign participants to groups in a way that minimizes bias.
Simple randomization
Simple...

Ovarian Cycle

Ovarian Cycle

The menstrual cycle includes a critical component known as the ovarian cycle, which undergoes two main phases each month—the follicular phase and the luteal phase. The follicular phase is variable and averaging around 14 days. Ovulation, triggered by a surge in luteinizing hormone (LH), marks the transition between the two phases. The second phase, the luteal phase, is relatively consistent, lasting approximately 14 days, and is marked by the activity of the corpus luteum. While a cycle...

Hormonal Regulation of the Menstrual Cycle

Hormonal Regulation of the Menstrual Cycle

The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...

Nondisjunction

Nondisjunction

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...

Hormonal Control of the Ovarian Cycle

Hormonal Control of the Ovarian Cycle

The ovarian cycle is meticulously regulated by the hypothalamic-pituitary-gonadal axis. This cycle orchestrates the release of a mature oocyte, essential for reproduction.
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...

Articles linked to this work by shared authors, journal, and citation graph.

Comparing genome-wide significant and chemosensory variants as instruments for dietary patterns in Mendelian randomization.

International journal of epidemiology·2026

Genetics of sensory nutrition.

The Proceedings of the Nutrition Society·2026

Multiscale analysis and functional validation of the cellular and genetic determinants of skeletal disease.

Nature genetics·2026

Dissecting the genetic architecture of knee alignment reveals its contribution to osteoarthritis risk.

medRxiv : the preprint server for health sciences·2026

Nutritional and dietary drivers in the pathogenesis of acute appendicitis: the nutrition-microbiome-genetic axis.

The Proceedings of the Nutrition Society·2026

Parental body mass index and offspring childhood body size and eating behaviour: A structural equation modelling analysis in the Norwegian Mother, Father and Child Cohort Study.

PLoS medicine·2026

See all related articles