Tsafrir S Kolatt, Yoel Shufaro, Shlomo Mashiach, Bernard Czernobilsky, Sarit Aviel-Ronen, Liat Apel-Sarid, Mazal Dahan, Yuval Or
{"title":"Revealing the uterine blood vessel network via virtual pathology.","authors":"Tsafrir S Kolatt, Yoel Shufaro, Shlomo Mashiach, Bernard Czernobilsky, Sarit Aviel-Ronen, Liat Apel-Sarid, Mazal Dahan, Yuval Or","doi":"10.1530/RAF-22-0135","DOIUrl":"10.1530/RAF-22-0135","url":null,"abstract":"<p><strong>Background: </strong>The distribution of the blood vessel network at any point in time in any body tissue, may provide valuable information with regards to the tissue condition and its angiogenesis functionality. The blood vessel three-dimensional network of the endometrium goes through a process of change over a relatively short period of 4 weeks on average. It is well accepted that this angiogenesis is closely related to the success or failure of the implantation of the embryo Objective and rationale: Our study aims to present a method to follow the three-dimensional evolution of the superficial blood vessel distribution in the endometrium throughout the uterine cycle.</p><p><strong>Method: </strong>This method utilizes differences in the observed broadband colors of the blood vessels in order to assess their depth coordinate below the endometrial tissue surface. We implemented the method using microscopic images of fresh, ex-vivo, endometrial samples of different cycle days to obtain the statistical evolution track of the superficial blood vessel population in both human and animal (swine) samples.</p><p><strong>Outcomes: </strong>In human samples we observed a systematic and consistent trend in the BV diameter distribution at different tissue depths. We demonstrate that the magnitude of this trend evolves throughout the course of the female cycle.</p><p><strong>Wider implications: </strong>This method has the potential to further our understanding of the mechanisms of angiogenesis in tissues other than the endometrium. We propose that this method may also contribute to more precise endometrial dating and may assist in more accurate determination of embryo transfer timing within IVF treatments.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/90/RAF-22-0135.PMC10083648.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9634293","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}
Dareen Mattar, Warakorn Cheewasopit, Moafaq Samir, Philip G Knight
{"title":"Does kisspeptin exert a local modulatory effect on bovine ovarian steroidogenesis?","authors":"Dareen Mattar, Warakorn Cheewasopit, Moafaq Samir, Philip G Knight","doi":"10.1530/RAF-22-0088","DOIUrl":"10.1530/RAF-22-0088","url":null,"abstract":"<p><p>Kisspeptin, a hypothalamic neuropeptide encoded by the KISS1 gene, has a pivotal role in promoting GnRH secretion in mammals. Kisspeptin and its receptor (KISS1R) are also expressed in certain peripheral tissues including gonads, suggesting intra-gonadal roles. Such actions at the level of the bovine ovary have not been explored previously. The current aims were to determine whether KISS1 and its receptor (KISS1R) are expressed in the bovine ovary and whether kisspeptin or a kisspeptin antagonist can modulate ovarian steroid production by cultured ovarian cells. Granulosa (GC) and theca interna (TC) were collected from antral follicles (3-18 mm) categorized into five class sizes. Early, mid and regressing corpora lutea (CL) were also collected for RT-qPCR analysis of KISS1 and KISS1R expression. Bovine TC and GC cultured under both non-luteinizing (serum-free) and luteinizing (serum-supplemented) conditions were treated for 4 days with kisspeptin-10 (10-10-10-6M) or kisspeptin antagonist (p234; 10-10-10-6M), alone and in combination with either FSH (GC), LH (TC) or forskolin (luteinized GC/TC). Steroid secretion (GC: oestradiol, progesterone; TC: androstenedione, progesterone; luteinized GC/TC: progesterone) was measured by ELISA and viable cell number determined by neutral red uptake assay. KISS1 and KISS1R transcripts were detected in TC, GC and CL with significant differences between follicle categories and CL stages. However, neither kisspeptin-10 nor kisspeptin antagonist affected steroid secretion or viable cell number in any of the four ovarian cell culture models. As such, the hypothesis that kisspeptin has a direct intra-ovarian role to modulate follicular or luteal steroidogenesis, or cell proliferation/survival, is not supported.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10855649","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":"Sperm cryopreservation for impaired spermatogenesis.","authors":"George Hughes, Sarah Martins da Silva","doi":"10.1530/RAF-22-0106","DOIUrl":"10.1530/RAF-22-0106","url":null,"abstract":"<p><p>Sperm cryopreservation for men with severely impaired spermatogenesis is one of the commonest reasons for short-term sperm storage, usually in advance of fertility treatment. Cryopreservation is generally very effective, although not all spermatozoa survive the process of freezing and thawing. This review considers various aspects of freezing sperm, including an overview of methods, appropriate use of cryoprotectants and practical considerations, as well as oxidative stress and mechanisms of cell cryodamage.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9226197","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}
Noof Abdulrahman Alrabiah, Constantine A Simintiras, Alexander C O Evans, Patrick Lonergan, Trudee Fair
{"title":"Biochemical alterations in the follicular fluid of bovine peri-ovulatory follicles and association with final oocyte maturation.","authors":"Noof Abdulrahman Alrabiah, Constantine A Simintiras, Alexander C O Evans, Patrick Lonergan, Trudee Fair","doi":"10.1530/RAF-22-0090","DOIUrl":"10.1530/RAF-22-0090","url":null,"abstract":"<p><p>Follicular fluid (FF), a product of vascular transudate and granulosa and thecal cell secretions, is the milieu that has evolved to support oocyte growth and maturation which plays a central role in oocyte quality determination. Therefore, a suboptimal FF composition may be reflected in compromised oocyte progression through maturation, fertilization or embryo development. To date, the composition of bovine FF remains understudied. To address this, we comprehensively characterized the metabolomic constituency of bovine FF in the period during which the oocyte undergoes meiotic maturation. More specifically, FF from pre (-24 h) and peri (-2 h) -ovulatory follicles was profiled by high-throughput untargeted ultra-high-performance liquid chromatography tandem mass spectroscopy. A total of 634 metabolites were identified, comprising: lipids (37.1%), amino acids (30.0%), xenobiotics (11.5%), nucleotides (6.8%), carbohydrates (4.4%), cofactors and vitamins (4.4%), peptides (3.6%) and energy substrates (2.1%). The concentrations of 67 metabolites were significantly affected by stage of follicle development, 33.3% (n=21) were reduced (P≤0.05) by a mean of 9.0-fold, whereas 46 were elevated (P≤0.05) by a mean of 1.7-fold in peri vs. pre -ovulatory FF. The most pronounced individual metabolite concentration decreases were hypoxanthine (98.9-fold), xanthine (65.7-fold), 17β-oestradiol (12.4-fold), and inosine (4.6-fold). In contrast, the greatest increases were in retinal (4.9-fold), 1-methyl-5-imidazoleacetate (2.7-fold), and isovalerylcarnitine (2.7-fold). This global metabolomic analysis of bovine FF temporal dynamics provides new information for understanding the environment supporting oocyte maturation and facilitating ovulation, that has the potential for improving oocyte quality both in vivo and in vitro.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/e4/RAF-22-0090.PMC9874974.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10658776","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}
L C Morley, M Debant, H J Gaunt, N A B Simpson, D J Beech
{"title":"Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies.","authors":"L C Morley, M Debant, H J Gaunt, N A B Simpson, D J Beech","doi":"10.1530/RAF-22-0100","DOIUrl":"10.1530/RAF-22-0100","url":null,"abstract":"<p><strong>Lay summary: </strong>Friction caused by blood flowing across cells that line blood vessels (endothelial cells) activates sensors of mechanical force. This produces nitric oxide (NO) which widens placental blood vessels, enabling more blood flow to the baby. This study sought to determine whether the mechanical sensor, Piezo1, is important for NO production in fetoplacental endothelial cells (FpECs) and whether the steps in this pathway are different in small for gestational age (SGA) babies, where placental blood flow is often altered. We showed that in healthy FpECs, blood flow increased NO signalling. We suggest that in SGA babies, FpECs have an increase in baseline levels of NO signalling, suggestive of a compensatory drive. Treating healthy and SGA cells with a Piezo1 chemical activator, Yoda1, upregulated NO signalling. This shows that Piezo1 is linked to NO and that in SGA, FpECs have the capacity to further increase NO. Further research will establish whether Piezo1 enhancement leads to increased blood flow in the placenta. If so, Piezo1 could be a new target for developing treatments to prevent poor growth of babies in the womb.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9159851","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}
Bethany Chung, Charlotte Greene, Alice Pearson, Lisa M Starrs, W Colin Duncan
{"title":"The impact of COVID-19 on the assessment and management of ectopic pregnancies.","authors":"Bethany Chung, Charlotte Greene, Alice Pearson, Lisa M Starrs, W Colin Duncan","doi":"10.1530/RAF-22-0073","DOIUrl":"https://doi.org/10.1530/RAF-22-0073","url":null,"abstract":"<p><strong>Lay summary: </strong>During the COVID-19 pandemic, the public delayed seeking medical help, which may have affected the impact of having an ectopic pregnancy. An ectopic pregnancy is when pregnancy tissue grows outside its normal position in the womb, and it can be life-threatening. It can be treated by non-surgical or surgical options, and any delay in seeking help can reduce the options for treatment and increase the need for more urgent management. We wanted to assess whether there were differences in the presentation and management of ectopic pregnancies in a major teaching hospital between 2019 (pre-COVID-19) and 2021 (COVID-19 period). We found that the pandemic did not cause a delay in seeking medical help or cause worse outcomes. In fact, immediate surgical treatment and time in the hospital were less during COVID-19, perhaps because of a desire to avoid admission to hospital. One outcome of COVID-19 is reassurance that we can safely use more non-surgical treatments for ectopic pregnancies.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/5f/RAF-22-0073.PMC10083650.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9697200","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}
Bonnie Grant, Anjali Pradeep, Suks Minhas, Waljit S Dhillo, Richard Quinton, Channa N Jayasena
{"title":"Survey of endocrinologists managing recovery from anabolic androgenic steroid induced hypogonadism.","authors":"Bonnie Grant, Anjali Pradeep, Suks Minhas, Waljit S Dhillo, Richard Quinton, Channa N Jayasena","doi":"10.1530/RAF-22-0097","DOIUrl":"https://doi.org/10.1530/RAF-22-0097","url":null,"abstract":"<p><strong>Lay summary: </strong>Anabolic steroids (also known as 'steroids') are banned drugs like testosterone, which make muscles bigger in men. These drugs are dangerous because they stop the testes from making natural testosterone and can cause heart attacks. Men stopping steroids have very low testosterone, which makes them feel weak, depressed, suicidal, infertile, and unable to have erections. We surveyed over 100 doctors to find out how they treat men giving up steroids. We report that doctors differ widely in the way they treat these men. Most doctors simply advise men to wait for the natural recovery of testosterone levels to happen. But 20% of doctors give men drugs to boost testosterone and make men feel better. Unfortunately, many patients had not recovered by the time of our survey. In summary, our survey highlights differences and limitations in the treatment of men giving up steroids. The use of steroids is increasing rapidly among young men, so we recommend further work to improve the treatment of men who are motivated to give up steroids.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117192","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}
Jennifer Dabel, Florian Schneider, Joachim Wistuba, Sabine Kliesch, Stefan Schlatt, Nina Neuhaus
{"title":"New perspectives on fertility in transwomen with regard to spermatogonial stem cells.","authors":"Jennifer Dabel, Florian Schneider, Joachim Wistuba, Sabine Kliesch, Stefan Schlatt, Nina Neuhaus","doi":"10.1530/RAF-22-0022","DOIUrl":"https://doi.org/10.1530/RAF-22-0022","url":null,"abstract":"<p><strong>Objective: </strong>Germ cells of transwomen are affected by gender-affirming hormone therapy (GAHT). Fertility will be lost after surgical intervention; thereby, fertility preservation becomes an increasingly imortant topic. This study investigated if the absolute number of spermatogonia in transwomen is comparable at the time of gender-affirming surgery (GAS) to that in pre-pubertal boys.</p><p><strong>Methods: </strong>We carried out a retrospective study of testicular tissues from 25 selected subjects, which had undergone a comparable sex hormone therapy regimen using cyproterone acetate (10 or 12.5 mg) and estrogens. As controls, testicular biopsies of five cisgender adult men (aged 35-48 years) and five pre-/pubertal boys (5-14 years) were included. Testicular tissues were immunohistochemically stained for MAGE A4-positive cells, the most advanced germ cell type. The number of spermatogonia per area was assessed. Clinical values and serum hormone values for FSH, LH, testosterone, free testosterone, estradiol and prolactin were determined on the day of GAS for correlation analyses.</p><p><strong>Results: </strong>Round spermatids were the most advanced germ cell type in 3 subjects, 5 had an arrest at spermatocyte stage, while 17 showed a spermatogonial arrest. On average, testicular tissues of transwomen contained 25.15 spermatogonia/mm3, a number that was significantly reduced compared to the two control groups (P < 0.01, adult 80.65 spermatogonia/mm3 and pre-/pubertal boys 78.55 spermatogonia/mm3). Linear regression analysis revealed that testes with higher weight and high LH contained more spermatogonia.</p><p><strong>Conclusion: </strong>Irrespective of treatment dose or duration, spermatogenesis was impaired. Spermatogonial numbers were significantly reduced in transwomen compared to the control groups.</p><p><strong>Lay summary: </strong>When transwomen go through treatment to confirm their gender, their germ cells are affected. They lose their fertility after surgery, so fertility preservation becomes an important topic. We carried out a study looking at tissue from testes of 25 people who had been through the same sex hormone therapy until surgery. Blood samples were also taken. As controls, samples were taken from the testes of cisgender boys and adult men. On average, the samples from the testes of transwomen contained a smaller number of early sperm cells compared to the two control groups. Regardless of the dose or length of hormone treatment, the fertility of transwomen was significantly reduced so that counseling about fertility preservation should be offered before hormone therapy.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276261","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":"Extracellular vesicles from seminal plasma to improve fertilizing capacity of bulls.","authors":"Anna Lange-Consiglio, Emanuele Capra, Noemi Monferrini, Simone Canesi, Giampaolo Bosi, Marina Cretich, Roberto Frigerio, Valentina Galbiati, Federica Bertuzzo, Francesco Cobalchini, Fausto Cremonesi, Bianca Gasparrini","doi":"10.1530/RAF-22-0037","DOIUrl":"10.1530/RAF-22-0037","url":null,"abstract":"<p><p>Seminal plasma contains extracellular vesicles (EVs) that vehicle RNA, proteins, and other molecules able to influence the biological function of sperm. The aim of this study was to improve the fertilizing capacity of male gametes of low-fertility bulls using EVs isolated by ultracentrifugation from the seminal plasma of a bull of proven fertility. After dose-response curve, 10×106 sperm of low-fertility bulls were co-incubated for an hour with 400×106 EVs/ml. In addition, it has been verified that the incorporation of EVs, which takes place in the sperm midpiece, is maintained for 5 hours and even after cryopreservation. Subsequently, the spermatozoa of low-fertility bulls, with EVs incorporated, were used for the in vitro production of embryos. The rate of blastocyst at seventh day yield in vitro, with the use of sperm with EVs incorporated, increased by about twice the yield obtained with the same sperm in the absence of EVs: bulls having an average embryonic yield of 6.41±1.48%, 10.32±4.34% and 10.92±0.95% improved their yield to 21.21±1.99%, 22.17±6.09% and 19.99±5.78%, respectively (P<0.05). These encouraging results suggest that it might be possible to keep breeding bulls with poor fertility. Further studies will be needed to evaluate the in vivo fertility of sperm treated with EVs and understand how the content of EVs is involve in the sperm-vesicle interaction and in the improved sperm performance.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/ce/RAF-22-0037.PMC9782411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10472614","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}