Chromosome segregation in meiosis is controlled by a conserved pathway that culminates in Separase-mediated cleavage of the α-kleisin Rec8, leading to dissolution of cohesin rings. Drosophila has no gene encoding Rec8, and the absence of a known Separase target raises the question of whether Separase and its regulator Securin (Pim in Drosophila) are important in Drosophila meiosis. Here, we investigate the role of Securin, Separase and the cohesin complex in female meiosis using fluorescence in situ hybridization against centromeric and arm-specific sequences to monitor cohesion. We show that Securin destruction and Separase activity are required for timely release of arm cohesion in anaphase I and centromere-proximal cohesion in anaphase II. They are also required for release of arm cohesion on polar body chromosomes. Cohesion on polar body chromosomes depends on the cohesin components SMC3 and the mitotic α-kleisin Rad21 (also called Vtd in Drosophila). We provide cytological evidence that SMC3 is required for arm cohesion in female meiosis, whereas Rad21, in agreement with recent findings, is not. We conclude that in Drosophila meiosis, cohesion is regulated by a conserved Securin–Separase pathway that targets a diverged Separase target, possibly within the cohesin complex.

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART.Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing.Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively).Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

Background: Newborn ovary homeobox (NOBOX) gene plays a critical role in the transcriptional regulation of oocyte-specific genes. Previous studies have demonstrated a pathogenic effect of NOBOX variants on premature ovarian insufficiency (POI) patients. Poor ovarian response (POR) is a risk factor for POI. Therefore, genetic variants in the NOBOX gene may also be studied as risk factors for POR development. Aims: The aim of the study is to investigate the association between seven known NOBOX single-nucleotide polymorphisms (SNPs) and POR in Jordanian females. Settings and Design: This was a case–control study of 60 females with POR for controlled ovarian hyperstimulation and 59 healthy females with no history of reproductive problems. Blood samples were collected from the participants and seven SNPs of NOBOX gene were screened. Subjects and Methods: DNA was extracted from blood samples. Polymerase chain reaction with primers specific for seven known SNPs in NOBOX gene was used to amplify the specified region within the gene followed by Sanger sequencing. Results: The seven SNPs investigated in this study, namely, rs77587352 (c.271G>T, p. Gly91Trp), rs7800847 (c.349C>T, p. Arg117Trp), rs193303102 (c.907C>T, p. Arg303X), rs193303103 (c.1025G>C, p. Ser342Thr), rs193303104 (c.1048G>T, p. Val350Leu), rs201947677 (c.1064G>A, p. Arg355His), and rs146227301 (c.1856C>T, p. Pro619Leu), only represent the wild-type allele in both females with POR and healthy participants. Conclusions: The results show that only monomorphic genotype of the NOBOX variants was found in Jordanian females studied.

Identifying menopause-related breast cancer biomarkers is crucial for enhancing diagnosis, prognosis, and personalized treatment at that stage of the patient’s life. In this paper, we present a comprehensive framework for extracting multiomics biomarkers specifically related to breast cancer incidence before and after menopause. Our approach integrates DNA methylation, gene expression, and copy number alteration data using a systematic pipeline encompassing data preprocessing and handling class imbalance, dimensionality reduction, and classification. The framework starts with MutSigCV for data preprocessing and ensuring data quality. The Synthetic Minority Over-sampling Technique (SMOTE) up-sampling technique is applied to address the class imbalance representation. Then, Principal Component Analysis (PCA) transforms the DNA methylation, gene expression, and copy number alteration data into a latent space. The purpose is to discard irrelevant variations and extract relevant information. Finally, a classification model is built based on the transformed multiomics data into a unified representation. The framework contributes to understanding the complex interplay between menopause and breast cancer, thereby revealing more precise diagnostic and therapeutic strategies in the future. The explainable artificial intelligence model Shapley based on the XGBoost regressor showed the power of the selected gene expressions for predicting the menopause status, and the potential biomarkers included RUNX1, PTEN, MAP3K1, and CDH1. The literature confirmed the findings.