Journal of Reproductive Immunology最新文献

Objective

To evaluate the association of the Systemic Immune-Inflammation Index (SII), Systemic Immune-Response Index (SIRI), and Neutrophil-to-Lymphocyte Ratio (NLR) with Cesarean Scar Pregnancy (CSP)

Methods

This prospective case-control study was conducted in Ankara City Hospital perinatology clinic between 2022 and 2023. The diagnosis of CSP was made by transabdominal and transvaginal ultrasound. NLR, SII, and SIRI values were compared between those diagnosed with CSP (n=23) and healthy pregnancies (n=126) at the time of first admission.

Results

The study group had significantly higher NLR, SII, and SIRI values compared to the controls. Optimal cut-off values were 3.79 (69 % sensitivity, 78.2 % specificity), 1180.6 (76.7 % sensitivity, 72.7 % specificity), and, 1.9 (83.3 % sensitivity, 72.7 % specificity) for NLR, SII, and SIRI, respectively. When NLR, SII and SIRI values were compared between CSP cases and pregnant women who had previous history of cesarean section but did not have CSP, significantly higher SII values were observed in the CSP group. The optimal cut-off value of SII was found to be 804.4 in predicting CSP among cases with previous history of cesarean delivery (73.9 % sensitivity, 66.2 % specificity).

Conclusion

SII, SIRI, and NLR may be useful in predicting cesarean scar pregnancy in pregnant women.

Preeclampsia (PE) significantly contributes to obstetric complications and maternal mortality, yet its pathogenesis and mechanisms are not well understood. Sulfiredoxin-1 (SRXN1) is known for its antioxidant activity and its role in defending against oxidative stress; it is also linked to various cancers. However, the role of SRXN1 in PE remains unclear. Our study found a significant decrease in SRXN1 levels in the serum and placental tissues of patients with early-onset preeclampsia (EOPE). Similarly, a PE-like mouse model showed reduced SRXN1 expression. Our in vitro experiments showed that reducing SRXN1 impaired trophoblast viability, decreased invasion and migration, and led to cell death, primarily through ferroptosis. These results are consistent with analyses of placental tissues from EOPE patients. In summary, lower SRXN1 levels during pregnancy contribute to trophoblast ferroptosis, potentially affecting the development and progression of EOPE.

Infertility affects 15 % of couples in the US, and many turn to assisted reproductive technologies, including in vitro fertilization and subsequent frozen embryo transfer (FET) to become pregnant. This study aimed to perform a broad assessment of the maternal immune system to determine if there are systemic differences on the day of FET in cycles that result in a live birth compared to those that do not. Women undergoing FET of euploid embryos were recruited and blood was collected on the day of FET as well as at early timepoints in pregnancy. Sixty immune and angiogenic proteins were measured in plasma, and gene expression of 92 immune-response related genes were evaluated in peripheral blood mononuclear cells (PBMCs). We found plasma concentrations of interleukin-13 (IL-13) and macrophage derived chemokine (MDC) were significantly lower on the day of FET in cycles that resulted in a live birth. We also found genes encoding C-C chemokine receptor type 5 (CCR5), CD8 subunit alpha (CD8A) and SMAD family member 3 (SMAD3) were upregulated in PBMCs on the day of FET in cycles that resulted in live birth. Measurements of immune mediators from maternal blood could serve as prognostic markers during FET to guide clinical decision making and further our understanding of implantation failure.

The testicular consequences of acute epididymo-orchitis remain largely unelucidated in long-term damage, which might be a neglected factor for male infertility. In this study, the differential phenotype of testicular immune cell subpopulations in lipopolysaccharide (LPS)-induced mouse epididymo-orchitis were analyzed by flow cytometry on day 1, day 7, and day 28. The number of macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) steadily decreased in the testes with inoculation. Total F4/80^-CD11c⁺ dendritic cells (DCs) maintained a relatively stable level, whereas conventional type 1 dendritic cells (cDC1) increased gradually from day 1 to day 28. There was a lower number of CD4⁺ and CD8⁺ T cells at day 1 and day 7, and they had similar results with a ceiling level at day 28. The testes displayed a higher level of CD3⁺ T cells but a lower frequency of macrophages, cDC2, and neutrophils at 28 days post-inoculation compared with the epididymis. In summary, our data indicates acute epididymo-orchitis could lead to long-term damage in the testes, which is characterized by CD3⁺ T cell (including CD4⁺ and CD8⁺ T cells)-mediated immune responses.

Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and are important for placenta formation during early pregnancy. Recurrent pregnancy loss (RPL) is associated with abnormalities in endometrial extracellular matrix remodeling. This study aimed to elucidate the roles of MMP2 and MMP9 in RPL pathogenesis. In total, 295 women with a history of RPL and 101 controls were included in this genetic study. Genotype analysis was performed using polymerase chain reaction (PCR) restriction fragment length polymorphisms. For proteolytic analysis, decidua and villi were collected from 10 RPL-miscarried women with normal fetal chromosomes (NC) and 19 women with fetal chromosome aberrations (AC). The expression of MMP2 and MMP9 in the decidua and villi was measured by IHC and ELISA. All samples were collected after obtaining informed consent. There were no statistically significant differences in MMP2–735 C/T and MMP9–1562 C/T frequencies between women with RPL and the controls. There was no significant difference in MMP2 expression levels in the villi; however, MMP9 expression was significantly higher in normal fetal chromosomes. In the decidua, the expression of MMP2 in the NC group was significantly lower, and MMP9 in the NC group was significantly higher than in the AC group. Although no differences in MMP2–735 C/T and MMP9–1562 C/T gene polymorphisms were observed in the present study, it is suggested that differences at the protein level are involved in the pathogenesis of RPL since MMP expression is not only regulated by genes but also by local inflammation and various inductive signals.

Background and purpose

Epigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats.

Methods and materials

PE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50 mg/kg (High, H) from gestational day (GD) 6–17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured.

Results

EGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG.

Conclusion

EGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1.

Sperm-immobilizing antibodies (SI-Abs) are detected in the sera of 3 % of infertile women. SI-Abs are occasionally produced as allogeneic antibodies against sperm, causing immune infertility. SI-Abs inhibit the passage of sperm through the female reproductive tract. Research on anti-sperm antibodies (ASA) remains of great importance for population control. We aimed to identify the antigens recognized by SI-Abs and elucidate the pathogenesis of immune infertility. Twelve sperm-immobilization test (SIT)-positive and fourteen SIT-negative sera were analyzed by two-dimensional electrophoresis and western blotting. Antigenic materials were extracted from well-motile sperm prepared using 0.1 % sodium dodecyl sulfate. In total, 22 different spots were detected in the 12 positive sera. Among these, three positive serum samples showed two positive signals with similar migration patterns. The significant positive spots were Mr: 49 K, pI: 5.1 and Mr: 51 K, pI: 5.6. All these positive spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS); tubulin beta-4A (TBB4A) was identified from the spot Mr: 49 K, pI: 5.1. TBB4A is a major component of tubulin and constitutes the axoneme in the sperm tail and the centrosome in the sperm neck; it is generally located inside the cell. An authentic antibody against TBB4A showed a positive reaction in the sperm neck and tail regions in an immunofluorescence study. This antibody also inhibited sperm motility in a complement-dependent manner. Sperm membrane permeability reportedly changes during swimming and capacitation. We identified TBB4A as an antigenic molecule recognized by SI-Abs, which may be relevant to immunological contraception in the future.

Recurrent implantation failure (RIF) is a condition where a woman fails to obtain pregnancy after multiple embryo transfer cycles, even with superior-quality blastocysts. There are various factors that can contribute to RIF, including immunologic disturbances. The immune system is extremely important during pregnancy. Immune cells such as T cells, B cells, natural killer (NK) cells, and macrophages (MQ) are present in the female reproductive tract and are accountable for regulating the immune response to invading pathogens and maintaining tissue homeostasis. Dysregulation of these immune cells can lead to inflammation, which can impair fertility. One of the most common immunological disturbances observed in RIF is an altered Th1/Th2 ratio, along with changes in NK cell and macrophage numbers. In addition, the presence of some antibodies, such as anti-ovarian antibodies, can also contribute to RIF. Interleukins have been implicated in the development of an inflammatory response that can interfere with successful embryo implantation. As a result, a comprehensive understanding of immunological compartments in RIF women could assist us in determining the immunological origins of this disease. We will discuss immunological factors that might contribute to RIF etiology, including cellular and molecular components.

This review highlights over five decades of research on sperm-immobilizing antibodies (SI-Abs), which are crucial for understanding female infertility due to their effects on sperm motility and fertilization. Since the 1960s, Isojima et al. have made significant strides, notably with the Sperm Immobilization Test (SIT), which revolutionized the quantification of SI-Abs and their roles in infertility. Drawing from a comprehensive PubMed search on "the sperm immobilization test" and "sperm immobilizing antibody," our review underscores the critical insights gained into SI-Abs' impact on reproductive functions. SI-Abs result from the body's response to sperm antigens, potentially leading to infertility by affecting post-intercourse sperm function. However, the presence of anti-sperm antibodies does not guarantee infertility, indicating a complex relationship between these antibodies and reproductive outcomes. Isojima et al.'s pioneering studies paved the way for SIT and sperm immobilization titer (SI₅₀), tools that have clarified the link between SI-Abs and infertility, focusing on disrupted sperm mobility and fertilization as key infertility mechanisms. Clinically, interventions such as in-vitro fertilization (IVF), which bypasses or eliminates SI-Abs, have improved pregnancy rates, whereas Freund's complete adjuvant therapy has deepened our understanding of infertility mechanisms. The SI₅₀ value is crucial for predicting fertility treatment success and guiding therapeutic decisions based on antibody levels. In summary, the evolution of SI-Abs research has provided new hope for addressing infertility, significantly enriching the field of reproductive immunology, and highlighting the need for ongoing investigation.

Smoking during pregnancy is associated with negative reproductive outcome. Less is known about the impact of smoking or previous smoking in women with recurrent pregnancy loss (RPL) which this study aimed to investigate. We included all women <42 years (n=2829) referred to a RPL unit at Copenhagen University Hospital between January 2000 and December 2021 in the cohort with follow-up until June 2022. Patients were categorized as ‘smokers at time of referral’, ‘never-smokers’ or ‘former smokers’. The main outcomes were pregnancy history prior to referral, prospective pregnancy rate, live birth rate, rates of ectopic pregnancy, and stillbirth. At referral, smokers (n=373) were on average 2.0 years younger (P<0.001) and had experienced significantly more pregnancy losses (P<0.001), and stillbirths (P=0.01) compared to never-smokers (n=2100). Former smokers had a higher risk of stillbirth prior to referral compared to never-smokers but no differences in pregnancy rate or other outcomes. Prospective pregnancy rates were lower for smokers compared with never-smokers (71.8% vs. 77.5%, P=0.02). Live birth rate was 58.0% for the 243 women who smoked at referral compared to 61.4% for the 1488 never-smokers (P=0.32). Stillbirth and ectopic pregnancies were significantly more common for smokers (2.8% vs. 0.4%, P=0.01; 6.0% vs. 2.0%, P<0.008). Women with RPL who smoked at referral were referred younger with a higher number of previous pregnancy losses and stillbirths compared with never-smokers. Fewer smokers achieved a pregnancy after referral but those who did had a similar live birth rate compared to never-smokers, although stillbirths and ectopic pregnancies were more common.