Reproduction & fertility最新文献

{"title":"Improving access to sexual and reproductive health services among adolescent women in Zimbabwe.","authors":"M Mhlanga, A Mangombe, J J Karumazondo, T Yohannes","doi":"10.1530/RAF-24-0008","DOIUrl":"10.1530/RAF-24-0008","url":null,"abstract":"<p><strong>Background: </strong>Unplanned pregnancies increased among adolescents in Zimbabwe, resulting in unsafe abortions, sexual and gender-based violence, and forced marriages. Access to Sexual and Reproductive Health and Rights (SRHR) has been scanty among pregnant adolescents and adolescent mothers owing to negative social norms, stigma and discrimination. This project specifically targeted pregnant adolescents and adolescent mothers through a differentiated and targeted care approach to improve uptake and sexual and reproductive health outcomes.</p><p><strong>Methods: </strong>Target-specific peer support groups for pregnant adolescents and adolescent mothers were established in Epworth district of Zimbabwe. The Champions of Change, a peer-based approach, was used to facilitate comprehensive sexuality education. Mentors were adolescent mothers trained on how to use a tailor-made manual to facilitate sessions. Two health centers, namely Epworth Clinic and Overspill Clinic, were purposively selected to participate in this study. A total of 60 participants were recruited into this study, 30 from each clinic. Knowledge and attitude were measured using a semi-structured questionnaire administered before and after the intervention. A scorecard was used to assess friendliness and quality of service provision. A Chi-square test of association was used to determine the significance of the change in outcomes.</p><p><strong>Results: </strong>A significant improvement in knowledge of SRHR, attitudes, and healthcare-seeking behaviors was noted. There was a significant improvement in attitudes and friendliness in service provision. Access to services significantly increased with improvements in relationships and trust.</p><p><strong>Conclusion: </strong>A targeted and differentiated care approach increases the uptake of services and health outcomes among adolescent women by addressing their unique needs and circumstances.</p><p><strong>Lay summary: </strong>Adolescent pregnancy and motherhood have significantly risen in Zimbabwe with the advent of the COVID-19 pandemic. The condition of these adolescent women has been worsened by poor access to and utilization of sexual and reproductive health services by this unique group, resulting in poor sexual health outcomes. Pregnant adolescents and adolescent mothers are less likely to access sexual and reproductive health services due to heightened stigma and discrimination by peers, communities and service providers themselves. We adopted a peer-based approach to increase the agency of adolescent women and empower them through comprehensive sexuality education, engaging healthcare service providers, and improving parent-child communication. With our intervention, we noted a significant improvement in the proportion of pregnant adolescents and adolescent mothers accessing services and reporting improvement in relationships with parents and healthcare providers. We encourage health providers to consider providi","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FERTILITY CARE IN LOW AND MIDDLE INCOME COUNTRIES: Implementing fertility care: insights from a participatory workshop in The Gambia.","authors":"Anna Afferri, Susan Dierickx, Mustapha Bittaye, Musa Marena, Sainey M Ceesay, Haddy Bittaye, Allan A Pacey, And Julie Balen","doi":"10.1530/RAF-24-0029","DOIUrl":"10.1530/RAF-24-0029","url":null,"abstract":"<p><strong>Introduction: </strong>The Gambia, West Africa, has made recent progress on infertility, a component of sexual and reproductive health that is lagging behind others. Since 2016, there is favourable policy environment stemming from infertility research and partnership building with national stakeholders and local civil society organisations focussing on infertility. Here, we report outcomes from a participatory workshop on infertility policy implementation in The Gambia and provide insights on setting national priorities for fertility care in resource-limited settings.</p><p><strong>Methods: </strong>We conducted a participatory workshop involving 29 participants from Gambia's public and private health sectors. Using selected participatory group work tools, stakeholders identified and prioritised key activities within the framework of five pre-defined areas of action, including (i) creating guidelines/regulations; (ii) recording/reporting data; (iii) building public-private partnerships; (iv) training health providers; and (v) raising awareness and health-seeking.</p><p><strong>Results: </strong>A total of 17 prioritised activities were proposed across the five action areas, according to short-, medium-, and long-term timeframes. Three were further prioritised from the overall pool, through group consensus. A group model building activity helped to envision the complexity by elucidating links, loops, and connections between each activity and their expected outcomes.</p><p><strong>Conclusions: </strong>The participatory workshop identified actionable interventions for fertility care in The Gambia, with stakeholders setting a clear path ahead. Despite challenges, the continued engagement of Gambian policymakers, practitioners, researchers, and activists in efforts to move beyond policy creation to its implementation is essential. Improving fertility care in The Gambia and other low- and middle-income countries is feasible with effective collaboration and financial support.</p><p><strong>Lay summary: </strong>In The Gambia, a partnership of stakeholders from various domains, including research, grassroots activism, clinicians, and policymakers, contributed to an increased awareness of infertility. This, in turn, led to the inclusion of infertility in the national reproductive health strategic plan. An in-country participatory workshop involving participants from both public and private health sectors was held in October 2023 with the objective of identifying priorities for moving beyond planning to implementation, within the context of resource constraints. The top three identified priorities were: (i) training about infertility for health providers; (ii) harmonisation of data collection; and (iii) the development of clinical guidelines for infertility management. It is important for the Gambian Ministry of Health to implement these proposed locally relevant fertility care activities. Despite current and future challenges, having a clear v","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MICROBIOME: The trials and errors of developing an experimental model to study the impact of maternal gut microbiome disruption on perinatal asphyxia.","authors":"Mara Ioana Ionescu, Ana Maria Catrina, Ioana Alexandra Dogaru, Didina Catalina Barbalata, Cristian Ciotei, Cerasela Haidoiu, Vladimir Suhaianu, Gratiela Gradisteanu Pircalabioru, Siobhain M O'Mahony, Ana-Maria Zagrean","doi":"10.1530/RAF-24-0050","DOIUrl":"10.1530/RAF-24-0050","url":null,"abstract":"<p><strong>Abstract: </strong>Maternal gut microbiome impairment has garnered attention for its potential role in influencing neurodevelopmental outcomes in offspring, especially in situations that increase brain vulnerability such as perinatal asphyxia (PA). Maternal microbiome and fetal brain interplay emerge as a critical link between maternal health and offspring neurodevelopment. This study aims to generate a model to assess the impact of maternal dysbiosis triggered by gestational antibiotic administration and PA on offspring neurodevelopment. Wistar rats were subjected to antibiotics in drinking water from the 11th gestational day until birth. On the 6th postnatal day, pups were subjected to PA/normoxia, resulting in four experimental groups: control-normoxia, antibiotics-normoxia, control-asphyxia, and antibiotics-asphyxia. Early-life behavioral tests were conducted between postnatal days 7 and 9. The initial antimicrobial cocktail (ampicillin, vancomycin, neomycin, clindamycin, amphotericin-B) led to an increased number of miscarriages, poor weight gain during pregnancy, reduced offspring weight, and changes in the maternal gut microbiome compared to control. Offspring presented impaired neurodevelopmental reflexes in both PA and antibiotic groups and increased hippocampal neuroinflammation. Due to these detrimental effects, a more pregnancy-safe antibiotic cocktail was used for a second experiment (ampicillin, vancomycin, neomycin, meropenem). This resulted in no miscarriages or pregnancy-weight loss but was still linked to gut microbiome disruption. PA impaired neurodevelopmental reflexes and increased neuroinflammation, effects amplified by antibiotic administration. These preliminary findings reveal the cumulative potential of maternal dysbiosis and PA on neurodevelopment impairment, emphasizing caution in gestational antimicrobial use. Further investigations should include offspring long-term follow-up and maternal behavior and integrate probiotics to counteract antibiotic effects.</p><p><strong>Graphical abstract: </strong></p><p><strong>Lay summary: </strong>This study investigates the impact of maternal gut microbiome disruptions caused by gestational antibiotic treatment and low oxygen exposure shortly after birth on the development of the rats' babies. We found that both antibiotic exposure and reduced oxygen levels led to changes in early behavior and increased inflammation of the nervous tissue in the baby rats. Although using a different, potentially safer antibiotic combination reduced pregnancy complications, it still changed the bacteria in the mother's gut and worsened early behavior. These findings show that antibiotics during pregnancy can affect the developing brain of baby rats and careful consideration should be used before prescribing them. Future research will explore longer-term effects and potential medicines.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142396604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy and functional consequences of interactions between human spermatozoa and seminal fluid extracellular vesicles.","authors":"Cottrell T Tamessar, Amanda L Anderson, Elizabeth G Bromfield, Natalie A Trigg, Shanmathi Parameswaran, Simone J Stanger, Judith Weidenhofer, Hui-Ming Zhang, Sarah A Robertson, David J Sharkey, Brett Nixon, John E Schjenken","doi":"10.1530/RAF-23-0088","DOIUrl":"10.1530/RAF-23-0088","url":null,"abstract":"<p><strong>Abstract: </strong>Seminal fluid extracellular vesicles (SFEVs) have previously been shown to interact with spermatozoa and influence their fertilisation capacity. Here, we sought to extend these studies by exploring the functional consequences of SFEV interactions with human spermatozoa. SFEVs were isolated from the seminal fluid of normozoospermic donors prior to assessing the kinetics of sperm-SFEV binding in vitro, as well as the effects of these interactions on sperm capacitation, acrosomal exocytosis, and motility profile. Biotin-labelled SFEV proteins were transferred primarily to the flagellum of spermatozoa within minutes of co-incubation, although additional foci of SFEV biotinylated proteins also labelled the mid-piece and head domain. Functional analyses of high-quality spermatozoa collected following liquefaction revealed that SFEVs did not influence sperm motility during incubation at pH 5, yet SFEVs induced subtle increases in total and progressive motility in sperm incubated with SFEVs at pH 7. Additional investigation of sperm motility kinematic parameters revealed that SFEVs significantly decreased beat cross frequency and increased distance straight line, linearity, straightness, straight line velocity, and wobble. SFEVs did not influence sperm capacitation status or the ability of sperm to undergo acrosomal exocytosis. Functional assessment of both high- and low-quality spermatozoa collected prior to liquefaction showed limited SFEV influence, with these vesicles inducing only subtle decreases in beat cross frequency in spermatozoa of both groups. These findings raise the prospect that, aside from subtle effects on sperm motility, the encapsulated SFEV cargo may be destined for physiological targets other than the male germline, notably the female reproductive tract.</p><p><strong>Lay summary: </strong>A male's influence over the biological processes of pregnancy extends beyond the provision of sperm. Molecular signals present in the ejaculate can influence the likelihood of pregnancy and healthy pregnancy progression, but the identity and function of these signals remain unclear. In this study, we wanted to understand if nano-sized particles present in the male ejaculate, called seminal fluid extracellular vesicles, can assist sperm in traversing the female reproductive tract to access the egg. To explore this, we isolated seminal fluid extracellular vesicles from human semen and incubated them with sperm. Our data showed that seminal fluid extracellular vesicles act to transfer molecular information to sperm, but this resulted in only subtle changes to the movement of sperm.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A low concentration of choline chloride alters the developmental program of the bovine preimplantation embryo.","authors":"McKenzie Lj Haimon, Eliab Estrada-Cortés, Thiago Fernandes Amaral, Jeremy Block, Surawich Jeensuk, Tatiane S Maia, Quinn A Hoorn, Masroor Sagheer, João H Bittar, Peter J Hansen","doi":"10.1530/RAF-24-0058","DOIUrl":"10.1530/RAF-24-0058","url":null,"abstract":"<p><p>Choline is a known developmental programming agent of the bovine preimplantation embryo. Culture of the embryo with 1.8 mmol/L choline, a concentration much higher than in blood, alters development to cause increased weaning weight and other changes during the postnatal period. It was hypothesized here that choline exerts similar effects on the developmental program of the embryo when added at concentrations similar to those in peripheral blood (i.e., 4 mol/L). Oocytes were collected via ovum pick up and embryos were produced in vitro. Embryos were cultured until day 7 after fertilization in medium with 4 mol/L choline chloride, or, as a vehicle control, with an additional 4 mol/L sodium chloride. Blastocysts were transferred into recipients and pregnancy was diagnosed at approximately 28 d of gestation. Subsequent calves (n=37 for vehicle and n=35 for choline) were weighed at birth and at weaning. Addition of choline to culture medium did not affect the proportion of embryos that became blastocysts or the proportion of transferred blastocysts that produced a pregnancy. Birth weight was unaffected by treatment but calves derived from choline-treated embryos were heavier at time of weaning and gained more per day from birth until weaning than calves derived from embryos treated with vehicle. Results demonstrate that choline can act on the preimplantation embryo at a physiologically-relevant concentration to alter postnatal phenotype. Observations are further evidence for the importance of the first days of embryonic development for the phenotype of the resulting calf.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landscape of assisted reproductive technology access in India.","authors":"Prathima Tholeti, Shubhashree Uppangala, Guruprasad Kalthur, Satish Kumar Adiga","doi":"10.1530/RAF-24-0079","DOIUrl":"10.1530/RAF-24-0079","url":null,"abstract":"<p><p>Historically, infertility has been stigmatized in the Indian society, primarily due to societal norms that equate marriage with procreation. In twentieth century, India focused primarily on over-fertility in its family planning programs, with little attention given to the complexities of infertility. The introduction of Assisted Reproductive Technology (ART) in the late 1970s made a global revolution, including in India, offering hope to infertile couples. Despite a significant rise in ART clinics offering a wide range of treatment options in the recent years, challenges remain, particularly regarding the affordability. In India, ART is typically dominated by the private sector as government support remains limited. Efforts to standardize ART practices, including the establishment of the National ART & Surrogacy Registry and ART act aim to regulate, improve outcomes and curb unethical practice. Despite these advancements, the high cost of treatment cycles and lack of insurance coverage limit many couples' ability to undergo fertility treatment. Addressing these issues requires a multifaceted approach, including policy reform, increased public awareness, and the development of affordable treatment options to ensure broader access to reproductive care across India.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new decision-support tool in a multi-center randomized trial for personalized, optimized, and simplified fertility treatment in non-PCOS patients.","authors":"Urmila Diwekar, Shyam Gupta, Anjali Gahlan, Sumitra Hota, Kshitiz Murdia, Nitiz Murdia, Vipin Chandra, Nihar Bhoi, Sanjay Joag","doi":"10.1530/RAF-24-0013","DOIUrl":"10.1530/RAF-24-0013","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>This study aimed to evaluate the effectiveness of a clinical decision support tool, Opt-IVF, in achieving the following outcomes: reducing the total cumulative dosage of Gonadotropins (Gns) used during controlled ovarian stimulation cycles and reducing the repeated ultrasonograms (USG) for monitoring follicular growth without compromising the number of good quality blastocysts obtained. The study design employed a multi-center randomized trial. The study enrolled 115 women aged 25-45 years undergoing IVF. Among the participants, 55 were randomly assigned to the intervention group (Opt-IVF), and 60 were randomly assigned to the control group. The intervention involved using a clinical decision support tool, Opt-IVF, to guide Gn dosing and trigger dates. The participants in the intervention group required significantly lower cumulative Gn dosage. The intervention group had higher numbers of oocytes retrieved and M2 retrieved than the control group. The number of good-quality blastocysts, the good-quality blastocyst rate, the ovarian sensitivity index (OSI), and the pregnancy rate in the intervention group were significantly higher than in the control group. The utilization of the clinical decision support tool led to several positive outcomes, including eliminating the need for ultrasound exams after day 5, reducing the dosage of Gn required, and yielding significantly higher numbers of high-quality blastocysts and higher pregnancy rates. Thus, Opt-IVF can successfully provide a personalized, optimized, and simplified approach to superovulation. Opt-IVF consistently outperformed the clinical teams in most of the outcomes. Clinical trials registration: ClinicalTrials.gov (ID - NCT05811065). Date of Registration: 15 March 2023. Date of enrollment of the first subject: 20 March 2023.</p><p><strong>Lay summary: </strong>The high cost of IVF is a result of costly drugs, fixed prices for infrastructure, extensive testing required, and labor costs for physicians and other healthcare personnel. Superovulation, which involves the drug-induced release of multiple eggs needed for IVF, accounts for a significant share of these costs. Current approaches to superovulation involve almost daily monitoring of follicle development using ultrasound and/or blood tests. The daily dosage of stimulatory hormones is then prescribed by physicians based on empirical data and clinical experience. However, the dose is not optimized for each patient, and overstimulation complications can occur. The cost of testing and drugs makes this stage very expensive. To overcome the shortcomings of this system, we have developed a decision support tool (Opt-IVF) that can provide a personalized model-optimized dosage profile for each patient. The clinical results show that Opt-IVF optimizes and personalizes dosage, reduces testing, and provides better outcomes for patients.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Influencing the Timing of Ovarian Tissue Cryopreservation in Young Girls.","authors":"Valentina Pampanini, Lena Sahlin, Elina Holopainen, Mervi Taskinen, Mikael Koskela, Kim Vettenranta, Jaana Vettenranta, Tiina Laine, Claudia Anderson, Kirsi Jahnukainen","doi":"10.1530/RAF-24-0032","DOIUrl":"10.1530/RAF-24-0032","url":null,"abstract":"<p><p>The aim of this study was to identify pitfalls in ovarian tissue cryopreservation protocol from referral to surgical procedure and to analyze factors associated with chemotherapy exposure of the cryopreserved tissue and decreased ovarian function in a cohort of young girls at high risk of infertility. The study population comprised 200 girls eligible for ovarian tissue cryopreservation between 2002 and 2020 at the Children's Hospital of the University Central Hospital of Helsinki (Finland). Analyses included evaluation of the proportion of patients who underwent ovarian tissue cryopreservation, factors associated with patient selection and timing of ovarian tissue cryopreservation, and ovarian function during long-term follow-up in relation to oncological treatments. Lack of counselling was identified as the major reason for not receiving ovarian tissue cryopreservation. A longer interval from scheduling gonadotoxic therapy to cryopreservation correlated with a higher exposure to alkylating agents of the ovarian tissue. The long-term ovarian function was mainly influenced by age at the time of gonadotoxic treatment. Current selection criteria for ovarian tissue cryopreservation should be implemented in order to stratify patients at risk of infertility and timely identify those at higher risk, especially in relation to age and pubertal stage. Efforts to increase healthcare providers' awareness and facilitate guided timing in relation to the treatment protocols are needed to guarantee early access to ovarian tissue cryopreservation for all patients at high risk of infertility.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Bench to Babies - Drug Development for Male Subfertility.","authors":"Shen Chuen Khaw, Sarah Martins da Silva","doi":"10.1530/RAF-24-0022","DOIUrl":"10.1530/RAF-24-0022","url":null,"abstract":"<p><p>Infertility is estimated to affect more than 50 million couples around the world, with male factor accounting for half of these cases, yet there is a notable absence of effective treatment options for men, other than in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). This review considers unlicensed and empirical treatments used for male subfertility, including hormonal therapy, phosphodiesterase inhibitors, and antioxidants. Compounds generally demonstrate variable improvements in sperm function but benefits for fertility are less clear. There is a pressing need for effective treatment options for subfertile men, however, our knowledge of sperm function is limited, restricting the identification of precise treatment targets. The traditional drug discovery pathway is also notorious for its extensive resource and time requirements, often extending over decades and demanding significant financial investment. Unfortunately, a substantial number of potential therapies fail before reaching the marketplace. Furthermore, reliance on mammalian models is not possible in the drug development process for male subfertility, due to significant variability between animals and man. We review recent breakthroughs and highlight novel methods aimed at improving the effectiveness and efficiency of drug discovery for male subfertility. High-throughput screening, combinatorial chemistry, and the repurposing of established medications have great potential. These strategies offer the promise of accelerating the pace of drug development, curbing the extensive demand for resources, and, in the case of drug repurposing, diminish the demand for comprehensive pharmacokinetic and pharmacodynamic studies. As these innovative approaches are adopted, the feasibility of addressing male subfertility through scientific advancements appears to be increasingly attainable.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression levels of the selenium-uptake receptor LRP8, the antioxidant selenoprotein GPX1 and steroidogenic enzymes correlate in granulosa cells.","authors":"Katja Hummitzsch, Jasmine E Kelly, Nicholas Hatzirodos, Wendy M Bonner, Feng Tang, Hugh H Harris, Raymond J Rodgers","doi":"10.1530/RAF-23-0074","DOIUrl":"10.1530/RAF-23-0074","url":null,"abstract":"<p><strong>Abstract: </strong>Reactive oxygen species (ROS) are a by-product of the activity of cytochrome P450 steroidogenic enzymes. Antioxidant enzymes protect against ROS damage. To identify if any particular antioxidant enzyme is used to protect against ROS produced by granulosa cells as follicles enlarge and produce oestradiol, we measured in the bovine granulosa cells the expression of two steroidogenic enzymes (CYP11A1, CYP19A1), important for progesterone and oestradiol production. We also measured the expression of the members (FDXR, FDX1, POR) of their electron transport chains (ETC). We measured antioxidant enzymes (GPXs 1-8, CAT, SODs 1 and 2, PRDXs 1-6, GSR, TXN, TXNRDs 1-3). Since selenium is an active component of GPXs, the selenium-uptake receptors (LRPs 2 and 8) were measured. Only the selenium-dependent GPX1 showed the same increase in expression as the steroidogenic enzymes did with increasing follicle size. GPX4 and PRDX2/6 decreased with follicle size, whereas SOD1/2, CAT, GSR, and TXNRD3 were lowest at the intermediate sizes. The other antioxidant enzymes were unchanged or expressed at low levels. The expression of the selenium-uptake receptor LRP8 also increased significantly with follicle size. Correlation analysis revealed statistically significant and strongly positive correlations of the steroidogenic enzymes and their ETCs with both GPX1 and LRP8. These results demonstrate a relationship between the expression of genes involved in steroidogenesis and selenium-containing antioxidant defence mechanisms. They suggest that during the late stages of folliculogenesis, granulosa cells are dependent on sufficient expression of GPX1 and the selenium transporter LRP8 to counteract increasing ROS levels caused by the production of steroid hormones.</p><p><strong>Lay summary: </strong>In the ovary, eggs are housed in follicles which contain the cells that produce oestrogen in the days leading up to ovulation of the egg. Oestrogen is produced by the action of enzymes. However, some of these enzymes also produce by-products called reactive oxygen species (ROS). These are harmful to eggs. Fortunately, cells have protective antioxidant enzymes that can neutralise ROS. This study was interested in which particular antioxidant enzyme(s) might be involved in neutralising the ROS in follicle cells. It was found that only one antioxidant enzyme, GPX1, appeared to be co-regulated with the enzymes that produce oestrogen and progesterone in the follicular cells. GPX1 contains the essential mineral selenium. In summary, this study has identified which antioxidant appears to be involved in neutralising ROS in the days leading to ovulation. It highlights the importance of selenium in the diet.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}