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Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids.

ABSTRACT: Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterized endometrial assembloids, consisting of gland-like organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma. We show that acute senescence in glandular epithelium drives secretion of multiple canonical implantation factors, whereas in the stroma it calibrates the emergence of anti-inflammatory decidual cells and pro-inflammatory senescent decidual cells. Pharmacological inhibition of stress responses in pre-decidual cells accelerated decidualization by eliminating the emergence of senescent decidual cells. In co-culture experiments, accelerated decidualization resulted in entrapment of collapsed human blastocysts in a robust, static decidual matrix. By contrast, the presence of senescent decidual cells created a dynamic implantation environment, enabling embryo expansion and attachment, although their persistence led to gradual disintegration of assembloids. Our findings suggest that decidual senescence controls endometrial fate decisions at implantation and highlight how endometrial assembloids may accelerate the discovery of new treatments to prevent reproductive failure.

SUBMITTER: Rawlings TM

PROVIDER: S-EPMC8523170 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Endometrial microbiome: sampling, assessment, and possible impact on embryo implantation.

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2024-07-17 | E-MTAB-13629 | biostudies-arrayexpress

Uterine SOX17: a key player in human endometrial receptivity and embryo implantation.

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Project description:Uterine glands are essential for pregnancy establishment. By employing forkhead box A2 (FOXA2)-deficient mouse models coupled with leukemia inhibitory factor (LIF) repletion, we reveal definitive roles of uterine glands in embryo implantation and stromal cell decidualization. Here we report that LIF from the uterine glands initiates embryo-uterine communication, leading to embryo attachment and stromal cell decidualization. Detailed histological and molecular analyses discovered that implantation crypt formation does not involve uterine glands, but removal of the luminal epithelium is delayed and subsequent decidualization fails in LIF-replaced glandless but not gland-containing FOXA2-deficient mice. Adverse ripple effects of those dysregulated events in the glandless uterus result in embryo resorption and pregnancy failure. These studies provide evidence that uterine glands synchronize embryo-endometrial interactions, coordinate on-time embryo implantation, and impact stromal cell decidualization, thereby ensuring embryo viability, placental growth, and pregnancy success.

| S-EPMC6015089 | biostudies-literature

Maternal anxiety affects embryo implantation via impairing adrenergic receptor signaling in decidual cells.

Project description:Recurrent implantation failure (RIF) is defined as the failed pregnancy after good embryo transfer over 3 cycles during in vitro fertilization (IVF).The human endometrium plays a vital role in providing the site for embryo implantation, with several factors implicated in unsatisfactory endometrial receptivity in RIF. Our present results revealed that women with pregnancy loss or infertility have a higher serum epinephrine level, indicating a potential correlation between psychological stress and pregnancy failure. RNA-sequencing of the tissues collected at the endometrial receptive phase in normal and RIF women showed that stress hormones could affect the functional status of endometrial receptivity. Subsequent analysis revealed that the epinephrine signaling acts as an important regulator of endometrial receptivity through the PI3K-AKT and FOXO1 signaling pathways. We also found that patients with RIF show attenuated expression of the alpha-2C-adrenergic receptor (ADRA2C) and that its down regulation induced by high level epinephrine could inhibit the decidualization. Early pregnant mice treated with stress showed high serum epinephrine levels, defective uterine adrenergic receptor expression, and low pregnancy rates. Altogether, our findings indicate that mental stress during early pregnancy can alter the functional status of endometrial receptivity.

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Project description: Not available

| S-EPMC9432137 | biostudies-literature

Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy.

Project description:Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11-/- mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. Moreover, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.

| S-EPMC6742226 | biostudies-literature

Endometrial pattern, but not endometrial thickness, affects implantation rates in euploid embryo transfers.

Project description:ObjectiveTo evaluate the relationship of endometrial thickness (EnT) and endometrial pattern (EnP) to euploid embryo transfer (ET) outcomes.DesignRetrospective cohort.SettingPrivate academic clinic.Patient(s)Patients (n = 277; age 36.1 ± 4.0 years) whose embryos (n = 476) underwent aneuploidy screening with fresh (n = 176) or frozen (n = 180) ET from July 2010 to March 2014.Intervention(s)The EnT and EnP were measured on trigger day and at ET. Patients were stratified by age and cycle type (fresh or frozen). Cycle data were combined at trigger day, but separated at ET day.Main outcome measure(s)Outcome measures were implantation rate, pregnancy rate, and clinical pregnancy rate. Analysis was conducted using χ(2) analysis and Fisher's exact test.Result(s)A total of 234 gestational sacs, 251 pregnancies, and 202 clinical pregnancies resulted from 356 cycles. The EnT (9.6 ± 1.8 mm; range: 5-15 mm) at trigger day (n = 241 cycles), as a continuous or categorical variable (≤8 vs. >8 mm), was not associated with implantation rate, pregnancy rate, or clinical pregnancy rate. The EnT at day of fresh ET (9.7 ± 2.2 mm; range: 4.4-17.9 mm) (n = 176 cycles) or frozen ET (9.1 ± 2.1 mm; range: 4.2-17.7 mm) (n = 180 cycles) was not associated with implantation rate, pregnancy rate, or clinical pregnancy rate. Type 3 EnP at trigger day was associated with increased serum progesterone at trigger and a decreased implantation rate, compared with type 2 EnP. The EnP at fresh or frozen ET was not associated with implantation rate, pregnancy rate, or clinical pregnancy rate.Conclusion(s)Within the study population, EnT was not significantly associated with clinical outcomes of euploid ETs. A type 3 EnP at trigger day suggests a prematurely closed window of implantation.

| S-EPMC4561002 | biostudies-literature

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