ArticleMolecular human reproduction2024
Murine uterine gland branching is necessary for gland function in implantation.
Article in Molecular human reproduction, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility.JCI insight · 2026Article
- Uterine collagen deposition fluctuates throughout the estrous cycle and provides a scaffold for gland visualization via theiScience · 2025Article
- Pre-implantation non-steroidal anti-inflammatory drug treatment disrupts mouse embryo spacing and post-implantation chamber morphogenesis.bioRxiv : the preprint server for biology · 2025Article
- Uterine stromal but not epithelial PTGS2 is critical for murine pregnancy success.Reproduction (Cambridge, England) · 2025Article
- Revolutionizing Implantation Studies: Uterine-Specific Models and Advanced Technologies.Biomolecules · 2025Review
- Foxa2-dependent uterine glandular cell differentiation is essential for successful implantation.Nature communications · 2025Article
- Loss of PRICKLE1 leads to abnormal endometrial epithelial architecture, decreased embryo implantation, and reduced fertility in mice.PNAS nexus · 2025Article
- Gut flora influences the hypothalamic-gonadal axis to regulate the pathogenesis of obesity-associated precocious puberty.Scientific reports · 2024Article
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Abstract
Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation; however, the contribution of uterine gland structure to gland secretions, such as LIF, is not known. Here, we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma, and muscle using the progesterone receptor PgrCre causes a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a Müllerian duct Cre line, Pax2Cre, displays gland bud elongation but a failure in gland branching. Reduction of ESR1 in adult uterine epithelium using the lactoferrin-Cre (LtfCre) displays normally branched uterine glands. Unbranched glands from Pax2Cre Esr1flox/flox uteri fail to express glandular pre-implantation Lif, preventing implantation chamber formation and embryo alignment along the uterine mesometrial-antimesometrial axis. In contrast, branched glands from LtfCre Esr1flox/flox uteri display reduced expression of ESR1 and glandular Lif resulting in delayed implantation chamber formation and embryo-uterine axes alignment but mice deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice express Lif in the luminal epithelium but fail to express Lif in the glandular epithelium, even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandular Lif expression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure-function contributes to pregnancy success.
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