Systems Biology in Reproductive Medicine最新文献

Polycystic ovary syndrome (PCOS) is a complex polygenic endocrinopathy affecting 5-20% of reproductive-age women. Familial studies, candidate gene studies, and GWAS have identified multiple PCOS-associated genetic loci. This study aims to identify the functional variants associated with PCOS. We applied whole exome sequencing (WES) to identify functional variants among eighty-five well-characterized women with PCOS. The annotated variants were filtered based on minor allele frequency and in-silico pathogenicity prediction. We found a significant association of 234 rare pathogenic nonsynonymous variants in 201 genes with PCOS in our study group. These genes are linked to steroid hormone biosynthesis, ovarian steroidogenesis, insulin resistance, and PI3K-Akt signaling pathway which are influential in PCOS pathophysiology. Further, several rare variants were found to be unique to women with and without insulin resistance, and enrichment analysis revealed that carbohydrate and lipid metabolism was especially deranged in insulin-resistant PCOS women. Variants of the steroidogenesis pathway were validated by Sanger sequencing including rs368902124 (CYP19A1), rs143286842 (IGF1R), and rs555458296 (BMP-6). In-silico analysis by DUET showed that these variants destabilized the folding of their corresponding protein. Women carrying these rare variants presented with altered hormonal profiles and clinical signs of hyperandrogenism and hyperinsulinemia, emphasizing their impact on PCOS pathophysiology. Several functional rare variants have been revealed to be associated with increased PCOS risk in the present study thus, expanding the genetic susceptibility landscape of Indian women to PCOS.

Cryopreservation, the use of very low temperatures to preserve structurally intact living cells and tissues, has seen exponential growth in the field of in vitro fertilization (IVF). In the last decade, cryopreservation of embryos and freeze-all protocols have become an essential aspect and a prerequisite for a successful IVF outcome. Moreover, vitrification, which is a fast and safe cryopreservation method, has proved to be an effective choice for cryopreserving gametes and embryos. The increasing number of cryopreserved embryos worldwide in cryobanks and IVF clinics is an undisputable fact that raises important physiological, ethical, and moral considerations that merit careful examination and discussion. Many couples utilizing assisted reproduction will have a surplus of cryopreserved embryos, in other words they already have completed their family without exhausting all the embryos that were created and cryopreserved during the process. Additionally, the global IVF market has also experienced significant growth due to various factors, including advancements in technology, increased awareness about infertility treatments, and changing societal norms towards delayed parenthood. Thus, for the foreseeable future the number of cryopreserved embryos, and the phenomenon of surplus embryos will likely remain unresolved. In the present review, following a description of the cryopreservation method and the physiological changes during the cryopreservation of embryos, the bioethical issues raised by the surplus cryopreserved embryos will be discussed alongside possible solutions for resolving this phenomenon.

Having a child is an innate trait in animals, including humans, and is required for the continued existence of all animal species. Therefore, for most women, the inability to conceive or to do so in a timely fashion - termed infertility - to enable the continuation of the family line can be emotionally distressing. The definition of infertility is controversial because of its separation into primary and secondary. This is further complicated by the loosely used term subfertility, which relates to couples who have reduced ability because they take longer than the natural time to conceive, as opposed to those who are infertile and are entirely unable to conceive after 6 to 12 months, depending on age. Infertility evaluation requires a thorough male and female history, physical examination of both partners, and targeted investigation to determine the cause of infertility in a particular couple. Various treatments apply to infertile couples depending on the age of the female partner, the results of investigations, the reason for infertility, the presence of inheritance of abnormal genes, the pregnancy rates the couple is happy with, the resources available, how desperate the couple is to achieve a live birth, and how much they want to commit to treatment. Infertility treatment could include counseling and expectant management only, intrauterine insemination in a natural or stimulated cycle, and IVF and or ICSI. Men with azoospermia will need surgical options to retrieve sperm for IVF/ ICSI, but rarely for IUI. This review overviews infertility's etiology, diagnosis, investigations, and treatment.

Indiscriminate use of polystyrene (PS) plastics has posed a major problem for its disposal and recycling on one hand, while on the other hand, fragmentation of these into micro/nano compounds threatens the living world by its toxic effect. The small sized particles can be present in any ecosystem and pose threat to the living world there. The unique properties of these small-scale fragments allow them to cross the barriers of human bodies and affect the vital organ system, altering the normal physiological parameters. Male reproductive system is highly affected by these micro/nanoplastics which leads to infertility and other physiological complications. Smaller number of literatures has been reported in this field in comparison to female reproductive system. The signaling mechanism of polystyrene micro/nanoplastics (PSMP/NPs) have been discussed in this review. There are lacunae in this regard which have been addressed very specifically. Many reports of biodegradation processes have been put forward, but not without any additional hazards. This review puts together the existing literature on the effect of PSMP/NPs on mammalian male reproductive system, throws light on the possible bioremediation methods using microorganisms, and highlights the unattended areas of study so that the future research finds a way for these problematic aspects.

Recurrent pregnancy loss (RPL) affects 1% to 5% of women of reproductive age, Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors about 75% of cases remaining unexplained. While the roles of hormonal imbalances, infections, and anatomical anomalies have been investigated, liver enzyme dysregulation and placenta previa remain poorly understood in their potential contributions to RPL. This study investigates these associations to improve outcomes for women with RPL. This study investigates the correlation between placenta previa, liver enzyme alterations, and recurrent pregnancy loss in a cohort of women from Telafar City. In a cross-sectional, case-control study, 80 non-pregnant women with a history of RPL were compared with 60 healthy controls without a history of miscarriage. Placental status was clinically assessed, and liver function was evaluated by measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). The study found that 79% of women with RPL exhibited placenta previa, a condition not observed in the control group. Additionally, women with RPL demonstrated significantly elevated levels of AST (19.7750 ± 5.5 U/L), ALT (17.7 ± 7.7 U/L), and GGT (21.9375 ± 9.5 U/L) compared to controls, while ALP levels were notably reduced in the RPL group (95.5250±35.5U/L vs. 124.650±19.6U/L). According to these results, placenta previa and liver enzyme dysregulation may play a role in the pathophysiology of recurrent pregnancy loss. In addition to the importance of being aware of the status of the placenta and liver function to avoid another miscarriage.

The embryonic aneuploidy in mammals may arise from impaired Spindle Assembly Checkpoint (SAC) function, a mechanism which prevents errors in chromosome segregation by blocking anaphase in response to spindle anomalies. Mammalian oocytes are particularly susceptible to these errors, possibly because the large oocyte volume favors dilution of the checkpoint signal, preventing its efficient function. This study aimed to investigate hypothesis that oocyte cytoplasmic volume affects SAC functionality. Oocyte size was manipulated in prophase oocytes (before nuclear envelope breakdown, NEBD) or in M-phase oocytes (after NEBD) by either reducing or increasing cytoplasmic volume by half. These oocytes were then cultured in the presence of nocodazole which activated the SAC by arresting oocytes in metaphase I of the first meiotic division. The functionality of SAC was assessed by measuring the proportion of oocytes escaping SAC-induced metaphase I arrest and completing the first meiotic division i.e., extruding the first polar body and entering the metaphase II of the second meiotic division. Reduction of the cytoplasmic volume in the prophase stage resulted in stronger checkpoint function, with only 4% of oocytes escaping SAC arrest compared to 36% of control normal-sized oocytes. Conversely, enlarged oocytes showed diminished checkpoint efficiency, with 54% bypassing checkpoint-induced arrest compared to 20% of control normal-sized oocytes. Importantly, no such relationship was observed when cytoplasmic volume was altered in oocytes after NEBD. This may suggest that the SAC depends on some nucleus-associated factors that are released into the cytoplasm after NEBD, since such factors would be twice as concentrated in oocytes undergoing volume reduction before NEBD compared to those undergoing reduction after NEBD. These results prove that SAC efficiency in mouse oocytes is influenced by cytoplasmic volume, with larger volumes impairing its function.

According to the World Health Organization (WHO), infertility is the failure of a couple to achieve pregnancy after one year of consistent unprotected sex. Male factors contribute to about 50 percent of all infertility cases. Male infertility is a multifactorial disease that can stem from multiple etiologies which can be congenital or acquired. Due to the complex nature of male infertility, a multifaceted approach is crucial for the diagnosis and treatment of the condition. But, in most cases, the cause of infertility is idiopathic. The diagnosis and management of male infertility is a comprehensive and stepwise process that involves history, physical examinations, and semen analyses which is the gold standard for evaluating male fertility in the clinic. The outcomes of semen analyses will determine the next step of investigation which may include hormone profiling, imaging, and genetic testing to identify the mechanism of infertility. Through advances in fertility research, Assisted Reproductive Technology has revolutionized the treatment approach for male infertility. ARTs like IVF and Intracytoplasmic sperm Injection have been useful in helping couples achieve pregnancy when all other treatment options have failed. Despite advances in fertility research, there are still challenges to be overcome such as improved access to fertility care, optimization of ART to achieve 100 percent clinical pregnancy, deeper understanding of etiologies of male infertility with emphasis on idiopathic male infertility. This review summarizes current knowledge on the etiologies, diagnosis, and therapeutic interventions as well as recent advances in basic and clinical research on male infertility.

Human fetal development requires sustenance via the placenta, which mediates molecular transport between maternal and fetal circulations. Placental formation begins as cells of the trophoblast lineage differentiate and the extraembryonic mesoderm becomes vascularized, assembling a unique organ de novo that facilitates nutrient and gas exchange, waste removal, hormone production and immune modulation. We describe how placentation is orchestrated to keep pace with fetal growth, but is vulnerable to disruption by medical interventions for infertility. Initially, trophoblast stem cells differentiate into proliferating mononuclear cytotrophoblasts (CTBs) that fuse to form the multinucleated syncytiotrophoblast (STB). The STB ensheathes the chorionic villi, bathed in maternal blood. As fetal blood vessels develop within the mesodermal core of villi, the maternal-fetal interface is established. Where the villi meet the decidua, CTBs further differentiate into extravillous trophoblasts, which invade and remodel uterine arteries into high-conductance, low-resistance vessels, enhancing maternal blood flow to the placenta. Among the critical intercellular axes that govern trophoblast differentiation, invasion, and vascular remodeling hormonal cues, particularly those associated with the corpus luteum, are critical; their alteration in certain assisted reproductive technology (ART) protocols can contribute to incomplete arterial remodeling. Malplacentation is linked to miscarriage, fetal growth restriction, and preeclampsia, affecting over 10% of pregnancies, and occurring at higher rates in patients diagnosed with infertility, especially those who conceive through ART. Understanding the mechanisms driving these pathologies is essential for improving pregnancy outcomes. Strategies to optimize ART protocols and therapeutic interventions targeting key signaling pathways offer potential avenues to mitigate risks associated with malplacentation.

Recent evidence suggests that individuals with polycystic ovary syndrome (PCOS) have an increased risk of developing mental health disorders and comorbidities linked to nervous system dysfunction. Interestingly, patients with schizophrenia (SCZ) often exhibit PCOS symptoms, indicating a possible connection between the two conditions. However, the underlying molecular links between these diseases remain poorly understood. We employed a comprehensive in-silico approach, utilizing publicly available datasets to investigate shared biomarkers candidates and key regulators involved in the development of PCOS and SCZ. We retrieved the datasets from the NCBI GEO database and differentially expressed genes (DEGs) were identified for each dataset. Common DEGs (cDEGs) were determined, and transcription factors (TFs) and miRNA targeting cDEGs were examined using the mirDIP portal and TRRUST database, respectively. We also assessed the TF-miRNA interactions by TransmiR database and constructed a regulatory network including TFs-microRNAs-cDEGs. Our analysis identified a total of 15 cDEGs that are regulated by 15 TFs and 8 mRNAs. Among our findings, we prioritized RELA as a potential TF regulator for both diseases, demonstrating synergistic interaction with four cDEGs (EGR1, CXCL8, IL1RN, IL1B) and seven microRNAs (hsa-miR-580, hsa-miR-5695, hsa-miR-936, hsa-miR-3675, hsa-miR-634, hsa-miR-603, hsa-miR-222) that target these genes. Our data highlights potential common biomarkers for PCOS and SCZ, presenting a novel regulatory network that elucidates the molecular mechanisms underlying both conditions. This emphasizes the importance of further research to explore new translational approaches, which may ultimately lead to improved diagnostic and therapeutic strategies for affected individuals.

Infertility and low birth rates have been threatening developed countries and have become a major socioeconomic problem that requires attention. To this end, germplasm preservation and subsequent fertility restoration with the aid of various assisted reproductive technologies (ART) have overcome many infertility issues over the last four decades. Particularly, cryopreservation offered various fertility preservation (FP) options for people with reproductive issues, gender dysphoria, and significantly expanded reproductive lifespan. The aim of this review is to provide the reader with the role that cryopreservation has played in human reproductive medicine (HRM) and family planning. We will first discuss the fundamentals of cryopreservation, including the development of cryopreservation methodologies for human reproductive cells and tissues, and how these techniques have helped address human infertility problems, as well as other ethical, legal, and social challenges. We will focus on literature regarding the current methodologies used in human infertility laboratories' clinical setting of the oocyte, sperm, and embryo, gonad cryopreservation, and discuss the latest issues related to the implementation of cryopreservation strategies used in HRM.