Silencing of Sex Chromosomes: from meiosis to early embryonic development

__Abstract__ In order to fit the whole genome into the cell nucleus, the DNA has to be organized into a condensed structure. The basic structure is the double helix structure of the DNA. The formation of nucleosomes mediates the first level of condensation: 147 base pairs of the double helix of DNA is wrapped around an octamer of two of each of the his tones H2A, H2B, H3 and H4 in 1.67 turns The complex of core histone proteins and the DNA that is folded around it, is the most simple form of chromatin. The nucleosomes are org

Clinical Relevance of Vaginal and Endometrial Microbiome Investigation in Women with Repeated Implantation Failure and Recurrent Pregnancy Loss

Recent studies have investigated if and how the vaginal and endometrial microbiome might affect endometrial receptivity and reproductive health. Although there is no consensus on the existence of a core uterine microbiome yet, evidence shows that the dominance of Lactobacillus spp. in the female reproductive tract is generally associated with eubiosis and improved chances of successful implantation and an ongoing pregnancy. Conversely, vaginal and endometrial dysbiosis can cause local inflammation and an increase of pro-inflammatory cytokines, compromising the integrity and receptivity of the endometrial mucosa and potentially hampering successful embryonic implantation. This review provides a critical appraisal of the influence of the vaginal and endometrial microbiome as parts of the female reproductive tract on fertility outcomes, focusing on repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It seems that RIF as well as RPL are both associated with an increase in microbiome diversity and a loss of Lactobacillus dominance in the lower female reproductive system.</p

Comparative Analysis of In Vitro Models to Study Antibody-Dependent Enhancement of Zika Virus Infection

During the 2015–2016 outbreak of Zika virus (ZIKV) in the Americas, a previously unknown severe complication of ZIKV infection during pregnancy resulting in birth defects was reported. Since the ZIKV outbreak occurred in regions that were highly endemic for the related dengue virus (DENV), it was speculated that antibody-dependent enhancement (ADE) of a ZIKV infection, caused by the presence of cross-reactive DENV antibodies, could contribute to ZIKV disease severity. Emerging evidence indicates that, while in vitro models can show ADE of ZIKV infection, ADE does not seem to contribute to congenital ZIKV disease severity in humans. However, the role of ADE of ZIKV infection during pregnancy and in vertical ZIKV transmission is not well studied. In this study, we hypothesized that pregnancy may affect the ability of myeloid cells to become infected with ZIKV, potentially through ADE. We first systematically assessed which cell lines and primary cells can be used to study ZIKV ADE in vitro, and we compared the difference in outcomes of (ADE) infection experiments between these cells. Subsequently, we tested the hypothesis that pregnancy may affect the ability of myeloid cells to become infected through ADE, by performing ZIKV ADE assays with primary cells isolated from blood of pregnant women from different trimesters and from age-matched non-pregnant women. We found that ADE of ZIKV infection can be induced in myeloid cell lines U937, THP-1, and K562 as well as in monocyte-derived macrophages from healthy donors. There was no difference in permissiveness for ZIKV infection or ADE potential of ZIKV infection in primary cells of pregnant women compared to non-pregnant women. In conclusion, no increased permissiveness for ZIKV infection and ADE of ZIKV infection was found using in vitro models of primary myeloid cells from pregnant women compared to age-matched non-pregnant women

Clinical Relevance of Vaginal and Endometrial Microbiome Investigation in Women with Repeated Implantation Failure and Recurrent Pregnancy Loss

Recent studies have investigated if and how the vaginal and endometrial microbiome might affect endometrial receptivity and reproductive health. Although there is no consensus on the existence of a core uterine microbiome yet, evidence shows that the dominance of Lactobacillus spp. in the female reproductive tract is generally associated with eubiosis and improved chances of successful implantation and an ongoing pregnancy. Conversely, vaginal and endometrial dysbiosis can cause local inflammation and an increase of pro-inflammatory cytokines, compromising the integrity and receptivity of the endometrial mucosa and potentially hampering successful embryonic implantation. This review provides a critical appraisal of the influence of the vaginal and endometrial microbiome as parts of the female reproductive tract on fertility outcomes, focusing on repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It seems that RIF as well as RPL are both associated with an increase in microbiome diversity and a loss of Lactobacillus dominance in the lower female reproductive system.</p

Gravid uterine torsion after prone positioning in SARS-CoV2 (COVID-19)-related acute respiratory distress syndrome

A multiparous pregnant patient was admitted to the intensive care unit in her third trimester of pregnancy for prone positioning mechanical ventilation after developing SARS-CoV2 (COVID-19)-related acute respiratory distress syndrome. Repositioning in left lateral tilt was followed by uterine contractions and cardiotocography alterations. Preterm caesarean section was performed based on persistent foetal tachycardia and suspected foetal distress, followed by a per-operative diagnosis of uterine levotorsion. This case report is the first to explore a potential causal link between prolonged prone positioning in late pregnancy and postural gravid uterine torsion and highlights the need for appropriate foetal monitoring during prone positioning mechanical ventilation support

The Vaginal Microbiome:Patient- versus Physician-Collected Microbial Swab: A Pilot Study

The composition of the vaginal microbiota prior to an IVF/IVF-ICSI treatment can predict the chance of achieving a pregnancy. To improve clinical applicability and be more patient-friendly, the self-collection of vaginal samples would be preferable. However, the reliability of patient-collected samples compared to physician-collected samples remains unclear. This study compares microbiome outcomes from patient-collected versus physician-collected vaginal samples. This is a prospective pilot study consisting of two cohorts: Cohort I involved patient self-sampling of the vagina, followed by a physician-collected vaginal swab, while Cohort II involved the reversed order of collection. The interspace profiling (IS-Pro) technique was used to analyze the microbiota composition in all samples. From May 2021 to March 2022, a total of 444 samples were collected from n = 222 patients (aged 21–44 years), with Cohort I (n = 109) and Cohort II (n = 113). The vaginal microbiome composition of both cohorts was highly similar, regardless of the sampling order, with a mean cosine similarity of 0.93 (95% CI 0.91, 0.95) in Cohort I and 0.94 (95% CI 0.92, 0.96) in Cohort II. Furthermore, ANOVA analysis revealed no significant differences in bacterial species abundance between physician- and patient-collected samples, nor between first and second sample collections. The self-collection of vaginal samples can be considered comparable to physician-collected samples and indicates a more patient-friendly and convenient collection of the vaginal microbiome in an outpatient clinical setting.</p

Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics

Scope: The effectiveness of maternal folate in reducing the risk of congenital malformations during pregnancy is well established. However, the role of the paternal folate status is scarcely investigated. The aim of this study is to investigate the evidence of associations between the paternal folate status and sperm quality, sperm epigenome, and pregnancy outcomes. Methods and results: Databases are searched up to December 2017 resulting in 3682 articles, of which 23 are retrieved for full-text assessment. Four out of thirteen human and two out of four animal studies show positive associations between folate concentrations and sperm parameters. An additional meta-analysis of four randomized controlled trials in subfertile men shows that the sperm concentration increases (3.54 95% confidence interval (CI) [−1.40 to 8.48]) after 3–6 months of 5 mg folic acid use per day compared to controls. Moreover, two out of two animal and one out of three human studies show significant alterations in the overall methylation of the sperm epigenome. One animal and one human study show associations between low folate intake and an increased risk of congenital malformations. Conclusions: This systematic review and meta-analysis shows evidence of associations between paternal folate status and sperm quality, fertility, congenital malformations, and placental weight

The Effect of an eHealth Coaching Program (Smarter Pregnancy) on Attitudes and Practices Toward Periconception Lifestyle Behaviors in Women Attempting Pregnancy: Prospective Study

Background: Lifestyle behaviors during the periconception period contribute to achievement of a successful pregnancy. Assessment of attitudes and practices toward these modifiable behaviors can aid in identifying gaps in unhealthy lifestyle behaviors with impact on intervention effectiveness. Objective: This study investigates the effectiveness of coaching by the eHealth program Smarter Pregnancy during the periconception period on improvement of attitudes and practices toward fruit and vegetable intake and smoking in women attempting pregnancy through assisted reproductive technology (ART) or natural conception. Methods: Women attempting pregnancy through ART (n=1060) or natural conception (n=631) were selected during the periconception period. The intervention groups, conceived through ART or naturally, received Smarter Pregnancy coaching for 24 weeks, whereas the control group conceived through ART and did not receive coaching. Attitudes and practices at baseline and follow-up periods were obtained from self-administered online questionnaire provided by the program. Attitudes were assessed in women with unhealthy behaviors as their intention to increase their fruit and vegetable intake and to quit smoking using a yes/no question. Outcomes on practices, suggesting effectiveness, included daily fruit (pieces) and vegetable (grams) intake, and if women smoked (yes/no). Changes in attitudes and practices were compared at 12 and 24 weeks with baseline between the ART intervention and ART control groups, and within the intervention groups between ART and natural conception. Changes in practices at 12 and 24 weeks were also compared with baseline between women with negative attitude and positive attitude within the intervention groups: ART and natural conception. Analysis was performed using linear and logistic regression models adjusted for maternal confounders and baseline attitudes and practices. Results: The ART intervention group showed higher vegetable intake and lower odds for negative attitudes toward vegetable intake after 12 weeks (βadj=25.72 g, P&lt;.001; adjusted odds ratio [ORadj] 0.24, P&lt;.001) and 24 weeks of coaching (βadj=23.84 g, P&lt;.001; ORadj 0.28, P&lt;.001) compared with ART controls. No statistically significant effect was observed on attitudes and practices toward fruit intake (12 weeks: P=.16 and .08, respectively; 24 weeks: P=.16 and .08, respectively) and smoking behavior (12 weeks: P=.87; 24 weeks: P=.92). No difference was observed for the studied attitudes and practices between the ART intervention and natural conception intervention groups. Women with persistent negative attitude toward fruit and vegetable intake at week 12 showed lower fruit and vegetable intake at week 24 compared with women with positive attitude (βadj=–.49, P&lt;.001; βadj=–30.07, P&lt;.001, respectively). Conclusions: The eHealth Smarter Pregnancy program may improve vegetable intake–related attitudes and practices in women undergoing ART treatment. Women with no intention to increase fruit and vegetable intake had less improvement in their intakes. Despite small changes, this study demonstrates again that Smarter Pregnancy can be used to improve vegetable intake, which can complemented by blended care that combines face-to-face and online care to also improve fruit intake and smoking behavior.</p

The Effect of an eHealth Coaching Program (Smarter Pregnancy) on Attitudes and Practices Toward Periconception Lifestyle Behaviors in Women Attempting Pregnancy: Prospective Study

Background: Lifestyle behaviors during the periconception period contribute to achievement of a successful pregnancy. Assessment of attitudes and practices toward these modifiable behaviors can aid in identifying gaps in unhealthy lifestyle behaviors with impact on intervention effectiveness. Objective: This study investigates the effectiveness of coaching by the eHealth program Smarter Pregnancy during the periconception period on improvement of attitudes and practices toward fruit and vegetable intake and smoking in women attempting pregnancy through assisted reproductive technology (ART) or natural conception. Methods: Women attempting pregnancy through ART (n=1060) or natural conception (n=631) were selected during the periconception period. The intervention groups, conceived through ART or naturally, received Smarter Pregnancy coaching for 24 weeks, whereas the control group conceived through ART and did not receive coaching. Attitudes and practices at baseline and follow-up periods were obtained from self-administered online questionnaire provided by the program. Attitudes were assessed in women with unhealthy behaviors as their intention to increase their fruit and vegetable intake and to quit smoking using a yes/no question. Outcomes on practices, suggesting effectiveness, included daily fruit (pieces) and vegetable (grams) intake, and if women smoked (yes/no). Changes in attitudes and practices were compared at 12 and 24 weeks with baseline between the ART intervention and ART control groups, and within the intervention groups between ART and natural conception. Changes in practices at 12 and 24 weeks were also compared with baseline between women with negative attitude and positive attitude within the intervention groups: ART and natural conception. Analysis was performed using linear and logistic regression models adjusted for maternal confounders and baseline attitudes and practices. Results: The ART intervention group showed higher vegetable intake and lower odds for negative attitudes toward vegetable intake after 12 weeks (βadj=25.72 g, P&lt;.001; adjusted odds ratio [ORadj] 0.24, P&lt;.001) and 24 weeks of coaching (βadj=23.84 g, P&lt;.001; ORadj 0.28, P&lt;.001) compared with ART controls. No statistically significant effect was observed on attitudes and practices toward fruit intake (12 weeks: P=.16 and .08, respectively; 24 weeks: P=.16 and .08, respectively) and smoking behavior (12 weeks: P=.87; 24 weeks: P=.92). No difference was observed for the studied attitudes and practices between the ART intervention and natural conception intervention groups. Women with persistent negative attitude toward fruit and vegetable intake at week 12 showed lower fruit and vegetable intake at week 24 compared with women with positive attitude (βadj=–.49, P&lt;.001; βadj=–30.07, P&lt;.001, respectively). Conclusions: The eHealth Smarter Pregnancy program may improve vegetable intake–related attitudes and practices in women undergoing ART treatment. Women with no intention to increase fruit and vegetable intake had less improvement in their intakes. Despite small changes, this study demonstrates again that Smarter Pregnancy can be used to improve vegetable intake, which can complemented by blended care that combines face-to-face and online care to also improve fruit intake and smoking behavior.</p