Reproductive Medicine and Biology最新文献

Background: Sperm motility and chemotaxis are important early steps in the interaction between sperm and oocytes during fertilization. Understanding these processes is essential for their basic biological and clinical applications. This review outlines advances in understanding the molecular mechanisms of sperm activation and chemotaxis over the past two decades.

Methods: The review focuses on the molecular pathways of Ca²⁺ signaling and the role of the CatSper channel involved in this signaling, and examines the comprehensive mechanisms that regulate sperm motility in aquatic invertebrates, fish, and mammals.

Main findings: Sperm are activated by environmental changes (e.g., pH and osmolality) and egg-derived factors. CatSper channels mediate Ca²⁺ influx and regulate cell motility and chemotaxis. In addition to Ca²⁺, cAMP and membrane potential are also involved in the regulation of sperm motility. Alternative pathways exist in species lacking CatSper, highlighting the diversity of sperm activation mechanisms.

Conclusion: There has been significant progress in understanding sperm motility regulation mediated by Ca²⁺, notably with CatSper, but the molecular mechanisms of other factors remain unclear. Future research should focus on species lacking CatSper to uncover commonalities and diversity in sperm motility regulation using genome editing and transcriptomic analyses.

Background: NR5A1 plays essential roles in the development of various tissues, including the ventromedial hypothalamus, pituitary gonadotrope, adrenal cortex, spleen, testis, and ovary. Additionally, NR5A1-positive cells in these tissues exhibit developmental and functional heterogeneity.

Methods: This review summarizes recent knowledge on the relationships between physiological functions and gene cascades regulated by NR5A1 in each tissue. In addition, we also present several intriguing examples of disparities in Nr5a1 gene regulation within the same tissues, which are relevant to developmentally and functionally heterogeneous cell populations.

Main findings: The adrenal cortex and testicular Leydig cells exhibit clear biphasic developmental processes, resulting in functionally distinct fetal and adult cell populations in which Nr5a1 is regulated by distinct enhancers. Similar heterogeneity of cell populations has been suggested in other tissues. However, functional differences in each cell population remain unclear, and Nr5a1 gene regulation disparities have not been reported.

Conclusion: Some steroidogenic tissues demonstrate biphasic development, with fetal and adult cell populations playing distinct and crucial physiological roles. Nr5a1 regulation varies across cell populations, and analyses of gene cascades centered on NR5A1 will aid in understanding the mechanisms underlying the development and maturation of reproductive capabilities.

Background: Macrophages are essential immune cells critical to reproductive physiology. They regulate key processes such as follicular development, ovulation, and luteinization in the ovaries. Macrophages are also involved in endometrial remodeling, immune tolerance, and placentation in the uterus.

Methods: This review examined the biological characteristics of macrophages and their role in ovarian, uterine, and fallopian tube physiology. It focused on findings from both animal and human studies to provide a comprehensive understanding of macrophage functions.

Main findings: In the ovaries, M1 macrophages play a role in folliculogenesis and ovulation through the inflammatory and angiogenic pathways. Macrophages also maintain the corpus luteum and vascular integrity. In the uterus, macrophages regulate tissue repair and remodeling during the menstrual cycle and play a critical role in implantation by maintaining immune tolerance and supporting decidualization. Dysregulation of the M1/M2 balance can cause implantation failure. In the fallopian tubes, macrophages mediate tissue repair and immune responses. Macrophage polarization dynamically adapts to physiological and pathological conditions in all reproductive organs highlighting the functional plasticity of these cells.

Conclusion: Macrophage polarization and functions are pivotal in maintaining reproductive health. Hence, understanding the role of macrophages in various reproductive organs provides a foundation for developing new therapies.

Background: Uterus transplantation is a groundbreaking solution for absolute uterine factor infertility, offering women the potential for full biological motherhood. Since the first human trial in 2012 and the birth of the first baby in 2014, over 140 procedures have been performed globally, resulting in more than 70 live births.

Methods: This review synthesizes data from foundational animal research, patient eligibility criteria, and advancements in surgical techniques for uterus transplantation. It examines live and deceased donor grafts, the role of assisted reproductive technologies, and obstetrical outcomes.

Main findings: Animal studies have been pivotal in transitioning uterus transplantation into clinical practice. Surgical advancements, including robotic-assisted live donor hysterectomy, have improved precision. Protocols for in vitro fertilization have evolved, optimizing treatment before and after transplantation and reducing the time between transplantation and embryo transfer. Obstetrical outcomes show increased risks, such as hypertensive disorders and preterm births, underscoring the importance of thorough monitoring during pregnancy.

Conclusion: Despite its complexities, uterus transplantation represents a transformative advance in reproductive medicine. It provides a viable path to biological motherhood for women with uterine infertility and marks significant progress in both transplantation and fertility treatments, paving the way for further refinement and broader application.

Background: Microdissection TESE has been considered the "gold standard" for retrieving testicular sperm in cases of non-obstructive azoospermia (NOA) despite limited scientific support. Here we compare all aspects of microdissection TESE with testis fine needle aspiration mapping (FNA Mapping) and directed TESE procedures for men with NOA.

Methods: We examine the history of testicular sperm extraction techniques and the rise of advanced technologies with a focus on microdissection TESE and FNA mapping. We summarize the published literature regarding the success rates, complications, and limitations of these two methods.

Main findings: As there are no randomized controlled trials, the best data come from the Cochrane Reviews, which include meta-analyses concluding that the simplest and safest methods of sperm retrieval should be chosen. Although microdissection TESE is popular, recent reports have questioned its value due to the significant hypogonadal consequences. Among alternative procedures, FNA Mapping is a viable and less invasive alternative to microdissection TESE in finding testicular sperm in NOA patients.

Conclusion: Alternatives to microdissection TESE procedures such as FNA Mapping offer several advantages that include similar sperm retrieval success rates, but also less invasiveness and improved understanding of the pathophysiology of NOA.

Purpose: To evaluate the impact of Endometrial Microbiome Metagenomic Analysis and Analysis of Infectious Chronic Endometritis (EMMA & ALICE) on pregnancy outcomes following recommended treatments in women with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL).

Methods: This prospective, multicenter cohort study included 527 women under 42 years old with RIF or RPL across 14 IVF centers in Japan. Endometrial samples were analyzed using EMMA & ALICE, and patients received antibiotics, probiotics, or no treatment based on test results. Pregnancy outcomes were assessed using Kaplan-Meier survival analysis and multivariate generalized linear models.

Results: Amongst participants, 43.4% had a normal Lactobacillus-dominated microbiota, 20.9% had dysbiosis, and 35.7% had mild dysbiosis or ultralow biomass. Kaplan-Meier analysis revealed significantly higher ongoing pregnancy rates in the dysbiosis group treated with antibiotics and probiotics compared to other groups (p = 0.031). Post-treatment, ongoing pregnancy rates in the dysbiosis and mild dysbiosis groups were comparable to the normal group.

Conclusions: EMMA & ALICE-guided antimicrobial and probiotic treatments improved pregnancy outcomes, enabling the dysbiosis group to achieve pregnancy earlier than the normal group. Addressing uterine dysbiosis may reduce the time to pregnancy in patients with RIF and RPL.

Trial registration: University Hospital Medical Information Network (UMIN), UMIN000036917.

Background: FIGLA is a transcription factor gene which plays a critical role in folliculogenesis. Consistent with this, FIGLA variants have been identified in females with non-syndromic primary ovarian insufficiency (POI) in both autosomal-dominant and autosomal-recessive forms.

Case description: We encountered two Japanese sisters who had secondary or primary amenorrhea at 15 years of age. They were diagnosed as having non-syndromic primary ovarian insufficiency (POI) with hypergonadotropic hypoestrogenism and markedly low serum anti-Müllerian hormone values.

Outcome: Whole genome sequencing revealed a novel homozygous missense variant, NM_001004311.3:c.338A>G:p.(Tyr113Cys), in FIGLA essential for folliculogenesis in the two sisters. The parents were heterozygous for this variant, and the heterozygous mother had regular menses at 51 years of age. This variant was extremely rare in public databases, and was invariably assessed as deleterious by six prediction tools. Furthermore, the p.(Tyr113Cys)-FIGLA protein was assessed as "pathogenic" or "likely pathogenic" by protein structural predictions, and was evaluated as "destabilizing" or "decrease stability" by protein stability predictions.

Conclusion: The results, in conjunction with the data reported in the literature, imply that FIGLA variants account for a small but certain fraction of non-syndromic POI, and pose a question as to the relevance of FIGLA variants to an autosomal dominant form of POI, although FIGLA variants have been identified in both autosomal dominant and autosomal recessive forms of non-syndromic POI.

Purpose: In vitro, oocyte development is susceptible to oxidative stress, which leads to endoplasmic reticulum (ER) stress. This study investigated whether the antioxidant melatonin attenuates ER stress and maintains oocyte-cumulus cell communication during the in vitro growth (IVG) of bovine oocytes.

Methods: Oocyte-granulosa cell complexes (OGCs) were harvested from slaughterhouse-derived ovaries and grown in vitro for 5 d at 38.5°C in 5% CO₂ humidified air. Melatonin (10^-7, 10^-9, or 10^-11 M) was added to the culture medium.

Results: Oocyte diameter increased on day 5 from its initial value in all groups. The antrum formation rate was significantly higher in the 10^-9 M melatonin-treated group than in the control. The melatonin-treated group showed reduced oxidative stress and increased gap junction communication compared with the control. ER stress-related genes in OGCs were significantly downregulated in the 10^-9 M melatonin-treated group compared with those in the control. No significant changes were found in subsequent maturation among groups; however, 10^-9 M melatonin treatment during IVG and IVM increased the maturation rate compared with that in the control.

Conclusions: Melatonin reduces oxidative stress, which attenuates ER stress in OGCs during IVG of bovine oocytes and may improve IVG efficiency in assisted reproductive technology.

Background: In vitro fertilization (IVF) and embryo transfer (ET) are widely used in reproductive biology. Despite the transfer of high-quality blastocysts, the implantation rate of IVF-derived blastocysts remains low after ET.

Methods: This article provides a comprehensive review of current research on embryo implantation regulators and their application to improve the implantation potential of IVF-derived blastocysts.

Main findings: The in vivo mouse model revealed selective proteolysis immediately after expression in activated blastocysts, that is, degradation of ERα expression in activated blastocysts regulated by the ubiquitin-proteasome pathway, followed by completion of blastocyst implantation. Treatment of blastocysts to induce appropriate protein expression during in vitro culture prior to ET is a useful approach for improving implantation rates. This approach showed that combined treatment with PRL, EGF, and 4-OH-E₂ (PEC) improved the blastocyst implantation rates. Furthermore, arginine and leucine drive reactive oxygen species (ROS)-mediated integrin α5β1 expression and promote blastocyst implantation.

Conclusion: Findings based on analysis of molecular and cellular regulators are useful for improving the implantation potential of IVF-derived blastocysts. These approaches may help to elucidate the mechanisms underlying the completion of the blastocyst implantation, although further investigation is required to improve the success of implantation and pregnancy.

Purpose: To compare risks of neonatal anomalies and obstetric complications among frozen-thawed embryo transfer (FET), fresh embryo transfer (FreshET), and non-assisted reproductive technology (non-ART) treatments in infertile women.

Methods: This retrospective cohort study analyzed 7378 singleton births (2643 non-ART, 4219 FET, 516 FreshET) from 2013 to 2022. Outcomes were compared using inverse probability weighting regression adjustment, with adjustment for maternal factors.

Results: After adjustment, the risk of neonatal anomalies did not differ significantly between FET and non-ART, or FreshET and non-ART. FET was associated with increased risks of obstetric complications compared with non-ART, including placenta accreta (adjusted risk difference [ARD] 3.61%, 95% CI 2.95-4.28), placenta previa (ARD 0.55%, 95% CI 0.14-0.96), postpartum hemorrhage (ARD 7.08%, 95% CI 6.03-8.13), gestational hypertension (ARD 3.57%, 95% CI 2.47-4.68), gestational diabetes (ARD 0.96%, 95% CI 0.17-1.75), and preterm birth (ARD 2.13%, 95% CI 1.23-3.02). FET also showed higher risk of high birth weight (ARD 0.97%, 95% CI 0.42-1.52). FreshET showed no significant differences in obstetric complications.

Conclusions: While the risk of neonatal anomalies did not differ among treatments, FET was associated with increased obstetric complication risks. These findings underscore the need for careful management of FET pregnancies and further research to improve treatment protocols.