F&S science最新文献

Objective

To study the role of interleukin (IL)-1β and the plasminogen activating (PA) system members in endometriotic stromal cell (ESC) migration/invasion.

Design

Primary cultures of ESCs.

Setting

Tertiary referral center for endometriosis and pelvic pain.

Patient(s)

Patients with surgically excised endometriosis.

Intervention(s)

Interleukin-1β stimulation of primary cultures of ESCs and knockdown of the PA system members urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-1 (PAI-1).

Main Outcome Measure(s)

Invasion/migration assays.

Result(s)

In primary cultures, IL-1β–stimulated ESC production of the PA system members uPA, uPA receptor, and PAI-1. Interleukin-1β also enhanced ESC migration and invasion, and these effects were inhibited by the IL-1 receptor-1 antagonist anakinra. Knockdown of each of the 3 PA system members also inhibited ESC migration and invasion. Knockdown of these PA system members further attenuated the impact of IL-1β on migration and invasion, suggesting that they mediated the promigration and proinvasion effects of IL-1β. To supplement the cell culture work, immunohistochemistry was performed on tissue sections of endometriotic epithelium/stroma: uPA, PAI-1, and IL-1β histoscores were not found to be correlated with each other.

Conclusion(s)

In primary cultures of ESCs, IL-1β induces migration and invasion, which is mediated by PA system members and inhibited by the drug anakinra. However, the immunohistochemistry expression of IL-1β, urokinase plasminogen inhibitor-1, and PAI-1 were not correlated, suggesting other regulatory mechanisms for PA system members. Inhibition of IL-1β (e.g., with anakinra) may have potential as a novel treatment approach for the migration/invasion of endometriosis.

Objective

To study the effect of intrauterine injection of C-X-C motif chemokine ligand 12 (CXCL12), also known as a stem cell chemoattractant (stromal cell-derived factor 1), on fertility and endometrial receptivity in mice with endometriosis.

Design

Laboratory study.

Setting

Academic Medical Center.

Animal(s)

Fifty-six mice underwent chemotherapy and bone marrow transplantation. Thirty-six of these mice underwent either surgery to induce endometriosis (n = 20) or sham surgery (n = 16).

Intervention(s)

Injection of CXCL12 as a potential therapeutic agent to improve fertility in endometriosis.

Main Outcome Measure(s)

Pregnancy rate, bone marrow–derived cell (BMDC) recruitment and endometrial receptivity markers.

Result(s)

The mice with or without endometriosis received a single uterine injection of either CXCL12 or placebo. Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. Mice were euthanized after delivery, and implantation markers homeobox A11, alpha-v beta-3 integrin, and progesterone receptor were analyzed by immunohistochemistry, whereas green fluorescent protein positive BMDC recruitment was quantified by immunohistochemistry and immunofluorescence. The sham surgery groups without endometriosis had the highest cumulative pregnancy rate (100%) regardless of CXCL12 treatment. The endometriosis group treated with placebo had the lowest pregnancy rate. An increased pregnancy rate was noted in the endometriosis group after treatment with CXCL12. There was also an increase in BMDC recruitment and endometrial expression of progesterone receptor and alpha-v beta-3 integrin in the endometriosis group that received CXCL12 compared with that in the endometriosis group that received placebo.

Conclusion(s)

Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. These results suggest that CXCL12 has a potential role as a therapeutic agent in women with infertility related to endometriosis and potentially other endometrial receptivity defects.

Objective

To study choriodecidual immunoreactivity of kisspeptin (KISS1) and its receptor (KISS1R) in recurrent pregnancy loss (RPL) due to aneuploidy (AnE) and unexplained (UE) RPL in comparison to control elective abortions (EAbs).

Design

This is a case-control study.

Setting

Tertiary care facility and affiliated research institute.

Patient(s)

Patients with either UE RPL (n = 10) or RPL due to AnE (n = 10) vs. a control group of patients who underwent EAb (n = 10).

Intervention(s)

Immunohistochemistry of archived choriodecidual tissue samples.

Main Outcome Measure(s)

Histoscores of KISS1 and KISS1R immunoreactivity in the syncytiotrophoblast (SyT), cytotrophoblast (CyT), decidual glands (DeGs), and decidual stroma (DeS) across the 3 study groups.

Result(s)

There was no difference in both maternal and gestational ages among the 3 groups. Kisspeptin immunoreactivity was similar in the SyT, CyT, DeGs, and DeS of all groups. Similarly, KISS1R expression was not different in the DeGs or DeS among all study groups. In addition, there was no difference in KISS1R immunoreactivity in the SyTs and CyTs between patients with RPL due to AnE and those with UE RPL. However, KISS1R was significantly lower in the SyT and CyT of patients with RPL due to AnE and UE RPL than in those who underwent EAb.

Conclusion(s)

The expression of KISS1R is lower in the chorionic tissues of euploid (unexplained) and aneuploid RPLs than in the control group. The current results broaden our understanding of the role played by KISS1 and KISS1R in early placentation. Further investigation is necessary to determine whether KISS1 activity is the cause or a sequel of defective placentation.

Objective

To study differences in cytokine expression profiles between women with ongoing pregnancy and those experiencing spontaneous miscarriage, among women who presented with threatened miscarriage before week 16 of gestation.

Design

Prospective cohort study.

Setting

Academic hospital.

Patient(s)

In this prospective cohort study, 155 pregnant women, comprising normal pregnant women recruited from antenatal clinics (n = 97) and women with threatened miscarriage recruited from an emergency walk-in clinic (n = 58).

Intervention(s)

None.

Main Outcome Measure(s)

Sixty-five serum cytokines quantified using multiplex immunoassay correlated with miscarriage outcomes.

Result(s)

Among women presenting with threatened miscarriage, those who eventually miscarried had significantly lower levels of interleukin (IL)-2, IL-12p70, IL-17A, B-cell–activating factor, B lymphocyte chemoattractant, basic nerve growth factor, interferon-γ, tumor necrosis factor–related apoptosis-inducing ligand, thymic stromal lymphopoietin, and tumor necrosis factor-α and higher levels of vascular endothelial growth factor A, IL-21, and stromal cell–derived factor 1α than those with ongoing pregnancy. Comparisons between normal pregnancies and women with threatened miscarriage who eventually miscarried revealed significant differences across 7 cytokines: B-cell–activating factor; B lymphocyte chemoattractant; basic nerve growth factor; IL-17A; fractalkine/CX3CL1; vascular endothelial growth factor A; and CCL22. Vascular endothelial growth factor A exhibited a negative correlation with the progesterone level (r = −0.270). The cluster of significant cytokines alludes to T cell proliferation, B-cell proliferation, natural killer cell–mediated cytotoxicity, and apoptosis as important pathways that determine pregnancy outcomes. Bioinformatic analysis further revealed alteration of the suppressor of cytokine signaling proteins family of Janus kinase-signal transducer and activator of transcription signaling axis by cytokines as a plausible key molecular mechanism in spontaneous miscarriage.

Conclusion(s)

This study demonstrates that the regulated balance between the proinflammatory and anti-inflammatory pathways is crucial to maintaining pregnancy. A better understanding of the cytokines associated with immunomodulatory effects may lead to novel targets for the prediction and treatment of spontaneous miscarriage.

Objective

To investigate whether blastocysts that divide irregularly reduce subsequent blastocyst euploidy.

Design

Retrospective study.

Setting

Private clinic.

Patient(s)

A total of 122 blastocysts for which consent for disposal and research use was obtained.

Intervention(s)

None.

Main Outcome Measure(s)

Results of next-generation sequencing analysis of the blastocysts and whether blastomeres by normal or irregular divisions subsequently participated in blastocyst formation or not.

Result(s)

The embryos were classified according to their dynamics until the second cleavage. The blastocyst euploidy rates were 33.3% (19/57) in the normal cleavage (NC) group, 38.3% (18/47) in the direct cleavage (embryos with one cell dividing into 3 cells) (DC) group, and 72.2% (13/18) in the reverse cleavage (RC) (embryos with fused cells once divided) group. The rate of the RC group was significantly higher than that of the NC group.

The blastocyst participation rate of the blastomeres were 95.6% in the NC group and 56.5% in that derived from DC of the first cleavage, and 91.7% in that of blastomeres derived from normal division of the second cleavage and 53.6% in that derived from DC of the second cleavage, both of which were significantly lower in the latter. In the RC group, the rates of fused and nonfused blastomeres were 62.1% and 87.5%, respectively, with no significant difference.

Conclusion(s)

The blastomeres generated by DC were often excluded from blastocyst formation, and we speculate that this is one reason why their division does not reduce blastocyst euploidy. The association between RC and euploidy of blastocysts merits further study.

Objective

To determine whether a curcumin-supplemented diet would prevent and/or treat uterine leiomyoma growth in our mouse xenograft model.

Design

Animal study.

Setting

Laboratory study.

Patient(s)

N/A.

Intervention(s)

Curcumin-supplemented diet.

Main Outcome Measure(s)

Dietary intake, blood concentrations, tumor size, extracellular matrix protein concentrations, apoptosis markers.

Result(s)

We found that curcumin was well tolerated as a dietary supplement, free curcumin and its metabolites were detected in the serum, and exposure resulted in approximately 60% less leiomyoma xenograft growth as well as dissolution of the peripheral extracellular matrix architecture of the xenografts. The production of matrix proteins, including collagens, decreased, whereas the number of apoptotic cells in the xenografts increased. Additionally, when xenografts were placed in a uterine intramural location, we found a significantly increased apoptotic response to curcumin in the diet.

Conclusion(s)

Mice on a diet supplemented with curcumin could achieve serum concentrations sufficient to regulate human leiomyoma xenograft growth, and curcumin could play both preventive and curative roles in the treatment of uterine leiomyoma as an oral nutritional supplement.

Objective

Lycopene (C40H56), a carotenoid found in red colour fruits, is known as a powerful antioxidant that protects cells from damage caused by reactive oxygen species (ROS). Etoposide inhibits topoisomerase II activity and restricts the development of cancer cells, though it establishes oxidative stress. To study the effect of lycopene (Ly) against hepatotoxicity and testis injury induced by etoposide in male rats.

Animals

Forty male Wister albino rats.

Settings

The experiment lasted for seven consecutive weeks including one week as acclimatization time.

Design

The experiment was in a completely randomized design with a 2×2 factorial arrangement.

Intervention(s)

The animals were grouped as follow: No etoposide injection and no lycopene (control), lycopene supplementation (LY), etoposide injection (ET), and rats with etoposide injection and lycopene supplement (ET+LY).

Main Outcome Measure(s)

At the end of the experiment, rats were sacrificed by cervical dislocation. Blood samples were harvested and analyzed for serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), low-density lipoprotein-Cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), total cholesterol (TC), Total Protein (TP), glucose (GLU) and testosterone. The left testis was manipulated for histological examination.

Result(s)

The result of experiment showed that rats with etoposide injection had higher ALT, AST, and ALP than the control rats. In contrast co-treated rats (ET+LY) significantly modulated the levels of the hepatic parameters. Administration of lycopene increased testosterone concentration and germinal epithelium of seminiferous tubules in testes rats.

Conclusion(s)

Lycopene might be a promising agent with hepatoprotective effect in restoring testis injury induced by etoposide in rats.

Objective

To evaluate the effect of chronic sleep deprivation on sperm function quality in mice.

Design

Experimental study.

Setting

Not applicable.

Animals

Spermatozoa from twenty-four 10-week-old C57BL/6J male mice.

Intervention(s)

The sleep deprivation group underwent gentle handling for 6 hours for 5 consecutive days. The mice in the sleep recovery group were allowed to sleep during the 24-hour period after the sleep deprivation protocol.

Main Outcome Measure(s)

After euthanasia, the spermatozoa were collected for analysis. Sperm motility was evaluated using computer-assisted sperm analyzer. Intracellular superoxide anion (O₂⁻) activity, acrosome integrity, mitochondrial activity, and DNA fragmentation assays were conducted afterward.

Result(s)

Sleep deprivation and sleep recovery groups presented a lower percentage of spermatozoa with an intact acrosome, compared with the respective control groups. Regarding DNA fragmentation, a decreased proportion of spermatozoa with Comet I class intact DNA was observed in the sleep recovery group, compared with the recovery control group. Beat cross frequency was increased in the sleep recovery group.

Conclusion(s)

Sleep deprivation can reduce sperm quality, impairing acrosome integrity. Sleep recovery decreased DNA integrity and increased beat cross frequency.

Objective

To systematically analyze the cell composition and transcriptome of primary human endometrial stromal cells (HESCs) and transformed human endometrial stromal cells (THESCs).

Design

The primary HESCs from 3 different donors and 1 immortalized THESC were collected from the human endometrium at the midsecretory phase and cultured in vitro.

Setting

Academic research laboratory.

Patient(s)

None.

Intervention(s)

None.

Main Outcome Measure(s)

Single-cell ribonucleic acid sequencing analysis.

Result(s)

We found the individual differences among the primary HESCs and bigger changes between the primary HESCs and THESCs. Cell clustering with or without integration identified cell clusters belonging to mature, proliferative, and active fibroblasts that were conserved across all samples at different stages of the cell cycles with intensive cell communication signals. All primary HESCs and THESCs can be correlated with some subpopulations of fibroblasts in the human endometrium.

Conclusion(s)

Our study indicated that the primary HESCs and THESCs displayed conserved cell characters and distinct cell clusters. Mature, proliferative, and active fibroblasts at different stages or cell cycles were detected across all samples and presented with a complex cell communication network. The cultured HESCs and THESCs retained the features of some subpopulations within the human endometrium.