Systems Biology in Reproductive Medicine最新文献

Sperm cryopreservation is a critical component of assisted reproductive technologies employed for both livestock breeding and human fertility management. Sperm are the highly specialized motile cells prone to cryodamage during freezing. Moreover, buffalo, pig and sheep sperm are more susceptible to cryoinjury leading to increased semen rejection rates and substantial economic losses due to reduced fertility. Advances in freezing protocols and modulation in composition of semen diluents protect sperm from cryodamage; however, inconsistency and inter-individual variability in semen freezability exist due to multifactorial etiology. The use of molecular technologies, particularly genomics, transcriptomics, proteomics, and metabolomics led to identification of potential biomarkers associated with cryotolerance. These omics-driven insights have not only enlightened our understanding of the molecular basis of cryoinjury but also has the potential in selecting bulls with good semen freezability. A multidisciplinary approach toward the development of targeted strategies such as supplementing extenders with novel cryotolerant biomolecules to mitigate the sperm damage. This review consolidates current knowledge on the molecular and physiological underpinnings of sperm cryodamage offering a holistic perspective that may guide refinement of existing cryopreservation protocols and extenders for improving sperm cryo-survivability in breeding males.

Polycystic ovary syndrome (PCOS) has an endocrine pathophysiology that needs immediate clinical attention for effective mitigation, as a significant portion of the reproductive population is affected globally. Current treatment options for PCOS are symptom-specific, and more extensive research is imperative to meet the therapeutic needs of the disease. Besides in vitro studies, the assessment of novel anti-PCOS drugs can be more effectively carried out through in vivo experimentation, for which the choice of appropriate animal models based on parameters and pathways to be evaluated is crucial. For a good preclinical evaluation, the animal model must ensure disease reproducibility and predictive validity. The present review provides insights into the animal models reported in the literature for PCOS studies and the aspects in which various therapeutics under study can be evaluated using these models. These animal models are also classified based on the mode of induction, duration essential for induction, and species. Besides, mammalian, non-mammalian and transgenic models are also included. This review will provide a detailed analysis to the researchers working in the domain of PCOS to facilitate an easy choice of appropriate animal model for their study and to identify the scope of developing newer animal models for PCOS study.

This review provides a comprehensive overview of the genetic factors underlying male and female infertility. Infertility affects an estimated one in six couples worldwide, with both male and female factors contributing equally to its prevalence. Approximately, 50% of infertility cases are attributed to genetic causes. We explore three main categories of genetic causes: chromosomal abnormalities, monogenic disorders, and syndromic conditions. Chromosomal causes, including numerical and structural aberrations, are discussed with a focus on their impact on gametogenesis and reproductive outcomes. We review key monogenic causes of infertility, highlighting recent discoveries in genes critical for gonadal development, gametogenesis, and hormonal regulation. Syndromic conditions affecting fertility are examined, highlighting their impact on reproductive function. Throughout the review, we address the challenges in identifying genetic mechanisms of infertility, particularly focusing on the intricate processes involved in oogenesis and spermatogenesis. We also discuss how advancements in genetic testing, such as next-generation sequencing (NGS) and genome-wide association studies (GWAS), have significantly enhanced our understanding of idiopathic infertility and promise further insights in the future. We also discuss the clinical implications of genetic diagnoses, including the role of preimplantation genetic testing (PGT) and genetic counseling in reproductive medicine. This review synthesizes current knowledge on the genetic basis of infertility, providing a comprehensive overview of chromosomal, monogenic, and syndromic causes. It aims to offer readers a solid foundation for understanding the complex genetic factors underlying reproductive disorders.

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.