Reproductive Medicine and Biology最新文献

Background: Mammalian spermatozoa have to be "capacitated" to be fertilization-competent. Capacitation is a collective term for the physiological and biochemical changes in spermatozoa that occur within the female body. However, the regulatory mechanisms underlying capacitation have not been fully elucidated.

Methods: Previously published papers on capacitation, especially from the perspective of ions/channels/transporters, were extracted and summarized.

Results: Capacitation can be divided into two processes: earlier events (membrane potential hyperpolarization, intracellular pH rise, intracellular Ca²⁺ rise, etc.) and two major later events: hyperactivation and the acrosome reaction. Earlier events are closely interconnected with each other. Various channels/transporters are involved in the regulation of them, which ultimately lead to the later events. Manipulating the extracellular K⁺ concentration based on the oviductal concentration modifies membrane potential; however, the later events and fertilization are not affected, suggesting the uninvolvement of membrane potential in capacitation. Hyperpolarization is a highly conserved phenomenon among mammalian species, indicating its importance in capacitation. Therefore, the physiological importance of hyperpolarization apart from membrane potential is suggested.

Conclusion: The hypotheses are (1) hyperpolarizing Na⁺ dynamics (decrease in intracellular Na⁺) and Na⁺-driven secondary active transporters play a vital role in capacitation and (2) the sperm-specific potassium channel Slo3 is involved in volume and/or morphological regulation.

[This corrects the article DOI: 10.1002/rmb2.12584.].

Background: Recent progress in molecular and signal analyses revealed essential functions of cellular signals including androgen and related growth factors such as Wnt regulators for external genitalia (ExG) development and its pathogenesis. Accumulated data showed their fundamental functions also for erectile tissue (corporal body) development and its abnormalities. The current review focuses on such signals from developmental and functional viewpoints.

Methods: Experimental strategies including histological and molecular signal analyses with conditional mutant mice for androgen and Wnt signals have been extensively utilized.

Main findings: Essential roles of androgen for the development of male-type ExG and urethral formation are shown. Wnt signals are associated with androgen for male-type ExG organogenesis. Androgen plays essential roles in the development of erectile tissue, the corporal body and it also regulates the duration time of erection. Wnt and other signals are essential for the regulation of mesenchymal cells of erectile tissue as shown by its conditional mutant mouse analyses. Stress signals, continuous erection, and the potential of lymphatic characteristics of the erectile vessels with sinusoids are also shown.

Conclusion: Reiterated involvement of androgen, Wnt, and other regulatory factors is stated for the development and pathogenesis of ExG and erectile tissues.

Purpose: To investigate the usefulness of an original dual artificial intelligence (AI) system, in which the first AI system eliminates the background of sliced tomographic blastocyst images, then the second AI system predicts implantation success using three-dimensional (3D) reconstructed images of the sequential images and conventional embryo evaluation parameters (CEE) such as maternal age.

Methods: Patients (from June 2022 to July 2023) could opt out and there was additional information on the Web site of the clinic. Implantation and non-implantation cases numbered 458 and 519, respectively. A total of 10 747 tomographic images of the blastocyst in a time-lapse incubator system with the CEE were obtained.

Results: The statistic values by the dual AI system were 0.774 ± 0.033 (mean ± standard error) for area under the characteristic curve, 0.727 for sensitivity, 0.719 for specificity, 0.727 for predictive value of positive test, 0.719 predictive value of negative test, and 0.723 for accuracy, respectively.

Conclusions: The usefulness of the dual AI system in predicting implantation of blastocyst in handling 3D data with conventional embryo evaluation information was demonstrated. This system may be a feasible option in clinical practice.

Background: Numerous efforts have been undertaken to identify biomarkers associated with embryo and oocyte quality to improve the success rate of in vitro fertilization. Metabolomics has gained traction for its ability to detect dynamic biological changes in real time and provide comprehensive metabolite profiles. This review synthesizes the most recent findings on metabolomic analysis of follicular fluid (FF) in clinical conditions leading to infertility, with a focus on the dynamics of energy metabolism and oocyte quality, and discusses future research directions.

Methods: A literature search was conducted without time constraints.

Main findings: The metabolites present in FF originate from five primary pathways: glycolysis, oxidative phosphorylation, lipid metabolism and β-oxidation, nucleic acid synthesis, and ketogenesis. Metabolomic profiling can broadly categorize infertile women into two groups: those with infertility due to aging and endometriosis, and those with infertility associated with polycystic ovarian syndrome and obesity. In the former group, glycolysis and lipid metabolism are upregulated to compensate for mitochondrial dysfunction, whereas the latter group exhibits the opposite trend. Assessing the levels of glucose, pyruvate, lactate, and plasmalogens in FF may be valuable for evaluating oocyte quality.

Conclusion: Metabolomic analysis, particularly focusing on energy metabolism in FF, holds promise for predicting female reproductive outcomes.

Background: Dietary interventions, recommended as a primary approach globally, benefit women with polycystic ovary syndrome (PCOS) by inducing weight loss and improving clinical symptoms, metabolism, and pregnancy results. However, the impact of diet on PCOS in individuals with BMI ≥ 25 kg/m² is unclear. The aim of this review was to offer dietary guidance for these patients.

Methods: Six databases, CNKI, Wanfang, VIP, PubMed, Cochrane Library, and Web of Science, were searched systematically from inception to December 2023 for clinical randomized controlled trials (RCT) on dietary interventions for PCOS. Two researchers independently screened and extracted data following pre-defined inclusion criteria, with bias assessment using the Cochrane Handbook and Review Manager (version 5.4) software.

Results: Nine RCTs with 559 participants were included. Among women with PCOS and obesity, compared to the control group, individuals who underwent dietary interventions experienced improvements in weight-related Indicators, glycolipid metabolism, hormone-related indicators, and fertility-related outcomes. Subgroup analysis indicated that calorie-restricted diets (CRDs) and low-energy-low-carb combined diets had advantages over other dietary interventions. Moreover, the overweight period was the optimal intervention period.

Conclusions: Dietary interventions can improve the clinical manifestations of PCOS and pregnancy rates in patients with a BMI ≥ 25 kg/m². Particularly, CRDs, low-calorie-low-carb combined diets, and low-calorie-extract combined diets are recommended.

Case: A 40-year-old Japanese man with nonobstructive azoospermia (NOA) was found to carry rare variants in KCTD19, a newly identified causative gene for spermatogenic failure. This patient was identified through mutation screening of KCTD19 in 97 men with etiology-unknown isolated NOA.

Outcome: The patient had two heterozygous variants in KCTD19 that affect consensus sequences of splice-donor sites [c.300+2T>A and c.2667C>T (p.E889E)]. Both variants were predicted to cause exon skipping. Long-read sequencing confirmed the compound heterozygosity of the variants. The patient exhibited small testes and a mildly elevated level of follicle-stimulating hormone but no other phenotypic abnormalities. Testicular histology showed borderline findings between spermatocyte maturation arrest and severe hypospermatogenesis.

Conclusion: These results provide evidence that biallelic loss-of-function variants of KCTD19 represent rare causes of isolated NOA.

Purpose: The purpose of this study is to confirm whether in vitro fertilization (IVF) with spermatozoa from Odf4-deficient infertile males (Odf4 ^-/- spermatozoa) can lead to the development of zygotes, which was reported in a previous in vivo study.

Methods: In vitro capacitation and IVF were performed using Odf4 ^-/- spermatozoa in a small drop of TYH medium with pyruvate and glucose, for 60 min or up to 4 days. A capacitation test was performed by immunoblotting using an anti-p-Tyr antibody. A sperm movement test was performed using a computer-assisted sperm motility analysis system (SMAS). An IVF fertilization test was also performed to evaluate zygote production. Videos were taken by a DMi8 stereomicroscope equipped with a high-speed camera.

Results: In in vitro condition, Odf4 ^-/- spermatozoa with hairpin flagella harboring large cytoplasmic droplets (CDs) underwent capacitation, about 30% of large CDs were removed from spermatozoa, and the flagella became straight (capacitation test). The Odf4 ^-/- spermatozoa with straight flagella swam forward (movement test) and fertilized Odf4 ^+/+ oocytes, which eventually developed into zygotes (fertilization test).

Conclusions: By conventional IVF, spermatozoa from Odf4-deficient male mice can fertilize oocytes that then develop into zygotes. These findings can be translated to human males with infertility caused by ODF4 deficiency.

Purpose: This study aimed to evaluate the protective effects of edible bird nest (EBN) against the detrimental impact of Wi-Fi on male reproductive health. Specifically, it examines whether EBN can mitigate Wi-Fi-induced changes in male reproductive hormones, estrogen receptors (ER), spermatogenesis, and sperm parameters.

Methods: Thirty-six adult male rats were divided into six groups (n = 6): Control, Control EBN, Control E2, Wi-Fi, Wi-Fi+EBN, and Wi-Fi+E2. Control EBN and Wi-Fi+EBN groups received 250 mg/kg/day EBN, while Control E2 and Wi-Fi+E2 groups received 12 μg/kg/day E2 for 10 days. Wi-Fi exposure and EBN supplementation lasted eight weeks. Assessments included organ weight, hormone levels (FSH, LH, testosterone, and E2), ERα/ERβ mRNA and protein expression, spermatogenic markers (c-KIT and SCF), and sperm quality.

Results: Wi-Fi exposure led to decreased FSH, testosterone, ERα mRNA, and sperm quality (concentration, motility, and viability). EBN supplementation restored serum FSH and testosterone levels, increased serum LH levels, and the testosterone/E2 ratio, and normalized mRNA ERα expression. Additionally, EBN increased sperm concentration in Wi-Fi-exposed rats without affecting motility or viability.

Conclusions: EBN plays a crucial role in regulating male reproductive hormones and spermatogenesis, leading to improved sperm concentration. This could notably benefit men experiencing oligospermia due to excessive Wi-Fi exposure.

Purpose: Recently, noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) using cell-free deoxyribonucleic acid has been developed; however, there are few reports on this and the results are inconsistent. This study was conducted to optimize the cultural environment.

Methods: We used 35 blastocysts that had been discarded after in-vitro fertilization. The concordance rate of karyotype analysis results between whole embryos (WEs), spent culture mediums (SCMs), and trophectoderms after 8, 16, and 24 h of culture was examined. Next, zona pellucida (ZP)-free blastocysts and then early blastocysts were cultured for 24 h each.

Results: Regarding the optimal culture times, the concordance rate between WEs and SCMs was 20%, 60%, and 100% at 8, 16, and 24 h, respectively. Significant differences were found between 8 and 24 h. The concordance rate with ZP cultures was 40.0%, and no significant differences were found. The concordance rate of early blastocysts thawed and cultured for 24 h was 40.0%, which was significantly lower than that of day 5 blastocysts.

Conclusions: The optimal culture times for niPGT-A were 24 h, and the concordance rate with free ZP was higher. The concordance rate for early blastocysts was low, suggesting that optimization of the conditions may be necessary.