Reproductive Medicine and Biology最新文献

Background: Mitosis maintains a genome's genetic information in daughter cells by accurately segregating chromosomes. However, chromosome aberrations are common during early mammalian embryogenesis. Chromosomal abnormalities during the early stages of embryogenesis result in the formation of mosaic embryos, wherein cells with normal genomes coexist with cells exhibiting abnormal genomes. The precise frequency and etiology of such abnormalities remain unclear. It is postulated that these aberrations contribute to the etiology of a number of conditions, including infertility and congenital diseases such as Down's syndrome.

Methods: This review synthesizes current literature and data to elucidate the causes and implications of chromosome aberrations in early mammalian embryos. It places particular emphasis on identifying patterns of mosaicism and investigating the underlying mechanisms responsible for these abnormalities.

Main findings: The underlying causes of chromosome abnormalities in early embryos were examined in the context of DNA replication and embryonic development.

Conclusion: A deeper understanding of chromosome abnormalities in early embryos could help develop new infertility treatments and advance research on cancers caused by these abnormalities. This article reviews current knowledge and gaps in understanding chromosome segregation abnormalities during embryogenesis and future directions in this field.

Purpose: This study aimed to investigate the molecular mechanisms associated with chromosome segregation errors caused by intrinsic oxidative stress during in vitro oocyte maturation (IVM) using oocytes from Sod1-deficient (Sod1KO) mice.

Methods: Ovulated or in vitro matured cumulus-cells oocyte complexes (COCs) were collected from wild-type (WT) and Sod1KO mice and evaluated chromosome alignment, chromosome segregation, meiotic progression, and BUBR1 and REC8 protein expression levels.

Results: In 21% O₂ IVM, the Sod1KO had significantly higher frequencies of chromosome misalignment and segregation errors compared to the WT, and they also reached Germinal Vesicle Break Down (GVBD) and M I stages peak earlier and showed a shorter M I stage residence time compared to the WT. These changes were associated with a decrease in the recruitment of BUBR1 to kinetochores at M I stage, but there were no differences in the expression of REC8 between the two genotypes. Furthermore, the addition of L-ascorbic acid (AsA) or N-acetyl-L-cysteine (NAC) during IVM reduced the frequency of chromosome segregation errors in Sod1KO oocytes.

Conclusions: Oxidative stress caused by Sod1 deficiency during IVM impairs the spindle assembly checkpoint function due to a decrease in the recruitment of BUBR1 to M I stage kinetochores, leading to abnormalities in meiotic progression and chromosome segregation.

Background: Uterine endometrial natural killer (uNK) cells represent major leukocytes in the mid-secretory phase of the cell cycle, and their number is further increased during early pregnancy. The activating and inhibitory receptors expressed on their surface mediate various functions of uNK cells, such as cytotoxicity, cytokine production, spiral artery remodeling, and self-recognition.

Methods: This study reviewed the most recent information (PubMed database, 175 articles included) regarding the activating and inhibitory receptors on uNK cells in human females with healthy pregnancies and the evidence indicating their significance in various reproductive failures.

Main findings: Numerous studies have indicated that the natural cytotoxic receptors, killer cell immunoglobulin-like receptors, and C-type lectin receptors, particularly those expressed on uNK cells, play crucial roles in successful pregnancy.

Conclusion: As studies on human uNK cells are limited owing to the low availability of fertile samples, and the extrapolation of animal models has certain limitations, the in vivo role of uNK cells has not yet been fully elucidated. However, immunotherapies focusing on modulating uNK cell function have been controversial in terms of pregnancy outcomes. Further research is required to elucidate the role of uNK cells in reproduction.

Background: Lipid droplets (LDs) are organelles consisting of a central core of neutral lipids covered by a single layer of phospholipids and are found in most eukaryotic cells. Accumulating evidence suggests that LDs not only store neutral lipids but also coordinate with other organelles for lipid metabolism within cells.

Methods: This review focuses on the synthesis of LDs during follicular development and highlights the factors involved in the regulation of LD biogenesis within the ovary.

Main findings: In the mammalian ovary, the presence of LDs has long been recognized mainly by morphological analysis. However, their distribution in the ovary varies according to the region and cell type; for example, LDs are abundant in the medulla, which has a rich blood vessel network, in interstitial cells, which are the site of steroid production, and surrounding growing follicles, while they are poor in granulosa cells within follicles. LDs are also enriched in the corpus luteum after ovulation and massively accumulate in atretic follicles during follicular growth. Furthermore, LD synthesis is synchronized with angiogenesis during follicular development.

Conclusion: Addressing the functional link between LD biogenesis and angiogenesis is essential for understanding the molecular basis underlying LD biology, as well as the ovarian dysfunction with metabolic disorders.

Background: Several conditions such as infertility, repeated implantation failure, and recurrent pregnancy loss can pose challenges in early pregnancy. These issues can be caused by the abnormal inflammatory response with various factors, including exogenous and endogenous agents, and pathogenic and nonpathogenic agents. In addition, they can be exacerbated by maternal immune response to the abovementioned factors.

Methods: This review aimed to assess the detrimental inflammatory effects of chronic endometritis, endometrial microbiota disturbance, and maternal immune system abnormalities on early pregnancy. Further, essential details such as ovulation, implantation, trophoblast invasion, and placental formation, were examined, thereby highlighting the beneficial roles of inflammation.

Main findings: Excessive inflammation was associated with various early pregnancy disorders. Meanwhile, a lack of appropriate inflammation could also contribute to the development of different early pregnancy complications.

Conclusion: Excessive inflammation and insufficient inflammation can possibly lead to abnormal conditions in early pregnancy, and appropriate inflammation is required for a successful pregnancy.

Purpose: This descriptive analysis evaluated the 2022 assisted reproductive technology (ART) data collected by the Japan Society of Obstetrics and Gynecology registry.

Methods and results: In 2022 (cutoff date 30 November 2023), 634 of 635 registered ART facilities participated; 602 implemented ART treatment, with 543 630 registered cycles and 77 206 neonates (9.1% and 10.6% increases from the previous year). For fresh cycles, freeze-all in vitro fertilization and intracytoplasmic sperm injection cycles increased, resulting in 2183 and 2822 neonates, respectively. In total, 275 296 cycles resulted in oocyte retrieval, with 158 247 (57.5%) freeze-all cycles. Total single embryo transfer (ET) and singleton pregnancy rates were 82.4% and 97.2%, respectively. The singleton live birth rate was 97.4%. The number of frozen-thawed ET (FET) cycles was 264 412, with 98 348 pregnancies and 72 201 neonates. The single ET rate was 85.3%. The rate of singleton pregnancies was 96.9%; that of singleton live births was 96.9%. Per registered cycle, women had a mean age of 37.6 (standard deviation: 4.8) years; 210 322 cycles (38.7%) were conducted for women aged ≥40 years.

Conclusions: Significant growth in ART cycles and outcomes reflects the impact of recent expanded insurance coverage.

Purpose: Sperm morphology and motility are major contributors to male-factor infertility, with many genes predicted to be involved. This study aimed to elucidate differentially expressed transcripts in human testis tissues of normal and abnormal spermatogenesis that could reveal new genes that may regulate sperm morphology and function.

Methods: Human testis biopsies were collected from men with well-characterized phenotypes of normal spermatogenesis, spermatid arrest, and Sertoli cell-only phenotype, and transcriptional differences were quantified by RNA-sequencing (RNA-Seq). Differentially expressed genes (DEGs) were filtered based on predominant expression in spermatids and gene functional annotations relevant to sperm morphology and motility. Selected 10 DEGs were validated by qRT-PCR and the localization of two proteins was determined in testis biopsies.

Results: The analysis revealed 6 genes (SPATA31E1, TEKT3, SLC9C1, PDE4A, CFAP47, and TNC) that are excellent candidates for novel genes enriched in developing human sperm. The immunohistochemical localization of two proteins, ORAI1 and SPATA31E1, in testis biopsies, verified that both are expressed in developing human germ cells, with SPATA31E1 enriched in late spermatocytes and spermatids.

Conclusion: This study identified human germ cell-enriched genes that could play functional roles in spermiogenesis and could thus be important in the development of morphologically normal, motile sperm.

Purpose: To investigate the effects of different controlled ovarian stimulation (COS) protocols, including the progestin-primed ovarian stimulation (PPOS), long, short, and the gonadotropin-releasing hormone antagonist protocols, on meiotic spindle visibility and position within the oocyte and clinical outcomes following ICSI.

Methods: Before ICSI, spindle position (θ) just below the polar body (PB) was defined as 0° and categorized as follows: θ = 0°, 0° < θ ≤ 30°, 30° < θ ≤ 60°, 60° < θ ≤ 90°, 90° < θ ≤ 180°, between the PB and the oolemma, and nonvisible. The clinical outcomes after ICSI were retrospectively analyzed.

Results: The normal fertilization rate was significantly higher in oocytes with visible spindles than in oocytes with nonvisible spindles after each COS protocol, but did not differ based on spindle positioning (0° ≤ θ ≤ 180°). The rates of pregnancy, live birth/ongoing pregnancy, and miscarriage did not differ based on spindle visibility or positioning. In multinominal logistic regression analysis, female age was associated with spindle position, and the odds of a spindle located at 30° < θ ≤ 60°, at 60° < θ ≤ 90°, or at 90° < θ ≤ 180° were increased relative to θ = 0° in older women (odds ratio; 1.020, 1.030, and 1.060, respectively; p < 0.05).

Conclusion: Meiotic spindle positioning in the oocyte does not affect normal fertilization, blastulation, pregnancy, live birth/ongoing pregnancy, and miscarriage after ICSI, independent of the COS protocol used.

Purpose: Polycystic ovary syndrome (PCOS) significantly affects women. This study investigated the association between serum anti-Müllerian hormone (AMH) levels and menstrual cycle disorders, and AMH for PCOS in a general cohort of young Japanese women.

Methods: We measured serum AMH levels in 528 healthy female students at two universities in Japan between 2014 and 2020. We investigated the association between serum AMH levels and hormone levels, menstrual cycle, and body mass index.

Results: The mean (±standard deviation) AMH level was 4.78 ± 2.88 ng/mL. Correlations were observed between serum AMH and luteinizing hormone (LH) or LH/follicle-stimulating hormone (FSH) levels in women with irregular menstruation (LH: r = 0.542, p < 0.001; LH/FSH: r = 0.584, p < 0.001). The optimal serum AMH cutoff value that predicted LH ≥7.1 IU/L and LH/FSH ≥1.21 (PCOS diagnostic criteria revised by Japan Society of Obstetrics and Gynecology) in women with menstrual irregularities was 5.30 ng/mL (area under the curve: 0.815, sensitivity: 84.2%, specificity: 70.3%).

Conclusions: Serum AMH can be measured during annual health checkups and may be a useful biomarker for early and arcuate diagnosis and intervention in women with PCOS.