Reproductive Medicine and Biology最新文献

Purpose: Testis is one of the most radiosensitive tissues. Interstitial stromal cells play a supportive role in male fertility, but radiation-induced damage to those cells has not yet been well understood. We aimed to investigate radiation-induced changes in interstitial stromal cells in the testis.

Methods: Adult male C57BL/6N mice (8 weeks) received a single pelvic exposure to a relatively high dose (1 Gy) or a very high dose (8 Gy) X-ray. We collected the testicular tissues for evaluation at 1, 9, and 60 days after irradiation.

Results: We detected a recoverable moderate degeneration of seminiferous tubules after 1 Gy exposure but an irreversible severe damage to the testis after 8 Gy exposure. Immunostaining results revealed that 1 Gy exposure induced DNA damage at day 1, upregulated intratubular GDNF at days 1 and 9, upregulated FGF at all time points, and upregulated CSF-1R at day 9. In contrast, 8 Gy exposure induced DNA damage at days 1 and 9, upregulated intratubular GDNF at days 1 and 9, downregulated CD105 at day 60, and upregulated FGF at all time points.

Conclusion: Radiation-induced dynamic changes to interstitial stromal cells in the testis. Upregulated interstitial CSF-1R and FGF2 may support spermatogenesis recovery after high-dose radiation.

[This corrects the article DOI: 10.1002/rmb2.12585.].

Background: The biological reproductive process requires the precise coordination of annual and daily signals to adapt to environmental shifts. Humans and animals have developed shared neuroendocrine systems that have adapted to process daily and seasonal light signals within the hypothalamic-pituitary -gonadal axis. However, the stability of circadian and seasonal biological processes is at risk due to industrialization and contemporary round-the-clock lifestyles. These threats include skipping breakfast, excessive artificial illumination during inappropriate hours because of irregular work schedules, nighttime urban lighting, and widespread environmental pollution from endocrine-disrupting chemicals. This review aimed to explore the interplay between lifestyle factors, circadian rhythms, and reproductive functions.

Methods: This review examined the reciprocal influences of circadian clocks on reproductive hormones, exploring the underlying mechanisms and their implications for fertility and reproductive health. We emphasized key findings regarding molecular clock components, endocrine pathways, and the critical importance of synchronizing circadian rhythms with hormonal cycles.

Main findings: The intersection of reproductive endocrinology and circadian biology reveals complex interactions between hormonal regulation and circadian rhythms. Circadian rhythm misalignments due to environmental factors, including late-night work and skipping breakfast, negatively impact endocrine and reproductive functions.

Conclusions: More strategies are needed to mitigate the effects of circadian disruption on reproductive functions.

Background: In vitro oocyte maturation (IVM) is not a novel concept; however, its wide-scale practice has been limited because of the lower clinical outcomes compared to conventional assisted reproductive technologies.

Methods: This comprehensive review addresses the significant advances made in oocyte in vitro maturation with the biphasic capacitation (CAPA)-IVM strategy applied to small ovarian antral follicles in humans over the last 10 years. CAPA-IVM consists of a prematuration phase wherein immature oocytes are temporarily meiotically arrested to gain competence before undergoing meiotic resumption.

Main findings: The integration of knowledge from basic research in animal models into clinical practice has led to a reevaluation of IVM for policystic ovary syndrome (PCOS) and onco-fertility patients. The introduction of meticulously conceived growth factors, hormonal supplements, and culture conditions led to an integrated biphasic CAPA-IVM system that promotes oocyte competence. A series of prospective randomized controlled studies validated the reproducible improvements in clinical outcomes and the safety of CAPA-IVM. So far, nearly 1000 babies have been born using this approach.

Conclusion: The use of CAPA-IVM in clinical studies has set the tone for major progress in the field and is achieving a safer, less expensive, and less emotionally loaded IVF experience, currently validated for PCOS patients.

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.