Reproductive Sciences最新文献

{"title":"Fat Mass and Obesity-Associated Protein Regulates Granulosa Cell Aging by Targeting Matrix Metalloproteinase-2 Gene Via an N6-Methyladenosine-YT521-B Homology Domain Family Member 2-Dependent Pathway in Aged Mice.","authors":"Linshuang Li, Le Yang, Lin Shen, Yiqing Zhao, Lan Wang, Hanwang Zhang","doi":"10.1007/s43032-024-01632-6","DOIUrl":"10.1007/s43032-024-01632-6","url":null,"abstract":"<p><p>In this study, we aimed to investigate the molecular mechanisms of RNA N6-methyladenosine (m6A) modification and how its associated proteins affect granulosa cell aging. A granulosa cell senescence model was constructed to detect the differences in total RNA m6A modification levels and the expression of related enzymes. Changes in downstream molecular expression and the effects on the cellular senescence phenotype were explored by repeatedly knocking down and overexpressing the key genes fat mass and obesity-associated protein (FTO), YT521-B homology domain family member 2 (YTHDF2), and matrix metalloproteinase-2 (MMP2). There was an increased total RNA m6A modification and decreased expression of the demethylase FTO and target gene MMP2 in senescent granulosa cells. FTO and MMP2 knockdown promoted granulosa cell senescence, whereas FTO and MMP2 overexpression retarded it. YTHDF2 and FTO can bind to the messenger RNA of MMP2. The extracellular signal-regulated kinase (ERK) pathway, which is downstream of MMP2, retarded the process of granulosa cell senescence through ERK activators. In granulosa cells, FTO can regulate the expression of MMP2 in an m6A-YTHDF2-dependent manner, influencing the activation status of the ERK pathway and contributing to the aging process of granulosa cells.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3498-3511"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of L-Tartaric Acid on Ovarian Histostereological and Serum Hormonal Analysis in an Animal Model of Polycystic Ovary Syndrome.","authors":"Sina Vakili, Farhad Koohpeyma, Mohammad Samare-Najaf, Bahia Namavar Jahromi, Morteza Jafarinia, Ali Samareh, Mohammad Hashem Hashempur","doi":"10.1007/s43032-024-01699-1","DOIUrl":"10.1007/s43032-024-01699-1","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most common endocrine-related reproductive disorder in women of reproductive age, accompanied by both the impairment of female fecundity and a risk of metabolic disorders. PCOS is emphasized as a worldwide concern due to its unknown etiology and lack of specific medications. The current study aimed to evaluate the effects of L-tartaric acid, an abundantly occurring compound in fruits, on the histostereological and hormonal changes caused by PCOS. Forty adult Sprague Dawley rats were randomly divided into four groups including controls (no intervention), Tartaric acid (40mg/Kg/day from day 21 onwards for 39 days), PCOS (21 days letrozole and then normal saline orally for 39 days), and PCOS + Tartaric acid. After treatments, the ovarian histostereological analysis as well as the level of reproductive hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, and testosterone was measured. PCOS caused a significant decrease in the number of unilaminar, multilaminar, antral, and graafian follicles and increased follicular atresia (p-value < 0.001). Moreover, the weight and volume of ovarian tissue and related structures including cortex, medulla, and cysts increased significantly (p-value < 0.0001). However, corpus luteum volume was significantly decreased (p-value < 0.001). Although significant differences were found in some parameters with the control group (p-value < 0.05), the administration of tartaric acid restored the pathological effects of PCOS on the ovarian histostructure. Furthermore, tartaric acid improved the serum levels of LH, estradiol, progesterone, and testosterone (p-value < 0.05). The obtained findings may suggest tartaric acid as a novel strategy for PCOS management, although further studies are necessary.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3583-3594"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Dietary Habits and the Semen Quality of South Asian Men Attending Fertility Clinic: A Cross-sectional Study.","authors":"Joydeep Chakraborty, Mahasampath Gowri, Treasa Joseph, Manimegalai Babuji, K Kavitha, Aleyamma T Kunjummen, Mohan S Kamath","doi":"10.1007/s43032-024-01710-9","DOIUrl":"10.1007/s43032-024-01710-9","url":null,"abstract":"<p><p>The purpose of the study is to explore the impact of dietary habits, including daily intake of nutrients and dietary patterns, on the semen characteristics of South-Asian men. This cross-sectional study included 162 South-Asian men aged 21-40 years who were undergoing infertility evaluation. Based on semen analysis, men were grouped into categories of normal and abnormal semen characteristics. The participants' dietary habits were captured using '24-hour dietary recall' and 'Food Frequency Questionnaire (FFQ)'. Daily dietary intake of various nutrients and adherence to prevalent dietary patterns were compared between men with normal and abnormal semen characteristics. Six dietary patterns were identified following factor analysis of FFQ data. Men with normal semen characteristics showed significantly higher consumption of \"coastal diet\" rich in seafood, fish, cereals, beans, and coconut oil than those with abnormal semen characteristics. Further, the multivariable-adjusted model, adjusted for clinically relevant confounders, like age, body mass index (BMI), physical activity, smoking and sexual abstinence, also showed a lower risk of abnormal semen characteristics among men consuming \"coastal diet\" (odds ratio [OR] = 0.56, 95% confidence interval [CI] 0.37-0.82). In terms of daily nutrient intake, men with normal semen characteristics showed significantly lower consumption of monounsaturated fatty acids (MUFA) compared to men with abnormal semen characteristics (p = 0.008). Our findings suggest that higher consumption of \"coastal pattern diet\" lowers the risk of abnormal semen characteristics. Additionally, a negative association of MUFA consumption with semen quality was also identified, which needs cautious interpretation until replicated in future studies with biochemical validations.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3368-3378"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Imaging Characteristics of Herlyn-Werner-Wunderlich Syndrome: a Comprehensive Analysis.","authors":"Jiani Qi, Ping Zhou, Hong Peng, Jin Deng, Yang Shao, Lingjuan Ye, Shengjuan Luo","doi":"10.1007/s43032-024-01628-2","DOIUrl":"10.1007/s43032-024-01628-2","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the clinical and imaging characteristics of Herlyn-Werner-Wunderlich syndrome (HWWS).</p><p><strong>Methods: </strong>This study presented an observational case series involving consecutive patients diagnosed with HWWS, whose medical records were retrospectively reviewed. From June 2012 to December 2022, there were a total of 85 patients with HWWS enrolled in our study. We obtained the medical history, including demographic characteristics, clinical presentation, treatment, complications, and radiologic examinations performed. Patients > 18 years of age (n = 58) were recontacted.</p><p><strong>Result: </strong>In our analysis, 27 patients were categorised as having complete obstruction, and 58 were categorised as having incomplete obstruction. The mean age at the onset of symptoms and diagnosis of complete obstruction was significantly younger than incomplete obstruction (P < 0.05). For complete obstruction, the median time between menarche and the onset of symptoms was 2.1 years, while for incomplete obstruction, it was 5.3 years. There was a significantly lower incidence of intermittent mucopurulent discharge, irregular vaginal haemorrhage, and occasional examination findings of complete obstruction than incomplete obstruction (P < 0.05). Complete obstruction was significantly associated with dysmenorrhea and pelvic endometriosis compared with incomplete obstruction (P < 0.05).</p><p><strong>Conclusions: </strong>There are distinct clinical differences between patients with complete obstruction of the hemivagina and those with incomplete obstruction. HWWS can manifest as various combinations of uterine anomalies, communications anomalies, and renal anomalies. Early recognition and treatment can avoid complications and preserve fertility.</p><p><strong>Keyswords: </strong>Herlyn-Werner-Wunderlich syndrome (HWWS); complete obstruction; incomplete obstruction; obstructed hemivagina; congenital malformation.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3343-3350"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of HOTAIR rs7958904 Polymorphism with Cervical Cancer Risk.","authors":"Afsana Akther, Md Shalahuddin Millat, Md Aminul Islam, Md Mazharul Islam Chowdhury, Md Abdul Aziz, Md Abdul Barek, S M Naim Uddin, Firoz Ahmed, Mohammad Safiqul Islam","doi":"10.1007/s43032-024-01679-5","DOIUrl":"10.1007/s43032-024-01679-5","url":null,"abstract":"<p><p>Cervical cancer (CC) has been the prominent cause of cancer-associated fatalities among women in developing countries. In terms of occurrence and mortality, it is ranked second in Bangladesh. Although different genetic polymorphisms linked with this cancer have been investigated over time, the association between the HOTAIR rs7958904 variant and cervical cancer is being reported for the first time in Bangladeshi women. RT-PCR-based TaqMan assay was employed to perform this case-control study on 200 cervical cancer patients and 148 healthy volunteers. Both cases and controls had average ages of 57.5 and 52.5 years, respectively. According to Hardy-Weinberg equilibrium, the rs7958904 allele of HOTAIR gene pretended no deviation for both cases and control groups. The genotyping results showed that rs7958904 has a significant correlation to the development of cervical cancer in different genetic association models, such as co-dominant 1 (CC vs. GG: OR = 1.67, p = 0.0435), co-dominant 2 (CC vs. GG: OR = 3.13, p = 0.0006), co-dominant 3 (CC vs. CG: OR = 1.88, p = 0.0384), dominant (CG + CC vs. GG: OR = 1.98, p = 0.004), recessive (CC vs. GG + CG: OR = 2.25, p = 0.005), and allele model (C vs. G: OR = 1.70, p = 0.0006). In conclusion, the HOTAIR rs7958904 variant has a substantial role in cervical cancer development in Bangladeshi women. Further functional studies with a larger population size are required to support our findings.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3420-3427"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Holistic Approaches in Endometriosis - as an Effective Method of Supporting Traditional Treatment: A Systematic Search and Narrative Review.","authors":"Agnieszka Mazur-Bialy, Sabina Tim, Anna Pępek, Kamila Skotniczna, Gabriela Naprawa","doi":"10.1007/s43032-024-01660-2","DOIUrl":"10.1007/s43032-024-01660-2","url":null,"abstract":"<p><p>Endometriosis is one of the gynecological diseases where women suffer from pain, quality of life decreased. The aim of this review was to describe the most common non-medical methods used in the treatment of symptoms associated with endometriosis and to determine their effectiveness. The review was performed in PubMed, Embase and Web of Science databases. Randomized controlled trials, case studies, observational studies, retrospective studies, prospective studies, pilot studies, trails, publications in English or Polish were searched based on the Participant-Intervention-Comparator-Outcomes-Study design (PICOS) format. The criteria used to select studies were: women with endometriosis, no cancer, included any physiotherapeutic or non-medical intervention. 3706 articles were found, however only 26 met the inclusion criteria and were included in the review. Quality of the studies was assessed by Risk of Bias 2 tool and ROBINS-1 tool. The most holistic approach used in the treatment of symptoms of endometriosis include physical therapy, manual therapy, electrophysical agents acupuncture, diet and psychological interventions. Most research has focused on relieving pain and increasing quality of life. Non-medical methods showed reduction of symptoms of endometriosis. Physical activity, manual therapy, electrophysical agents, acupuncture, diet and cognitive behavioral therapy showed no negative side effects and reduced pain, what improved the quality of life and reduced the perceived stress.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3257-3274"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assisted Reproductive Technology During COVID-19: A Population-Based Study Of Pregnancy Outcomes.","authors":"Shu Qin Wei, Thuy Mai Luu, Aimina Ayoub, Antoine Lewin, Nathalie Auger","doi":"10.1007/s43032-024-01649-x","DOIUrl":"10.1007/s43032-024-01649-x","url":null,"abstract":"<p><p>We assessed the impact of the COVID-19 pandemic on the pregnancy outcomes of patients who used assisted reproductive technology. We conducted a population-based cohort study of 443,101 patients who conceived naturally or with assisted reproductive technology between December 2015 and July 2021 and had a delivery in hospitals of Quebec, Canada. The main exposure measure was use of assisted reproductive technology before or during the pandemic. Outcomes included preeclampsia, preterm birth, and other pregnancy complications. We used adjusted log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of assisted reproductive technology with adverse pregnancy outcomes compared with natural conception before vs. during the pandemic. In secondary analyses, we examined the association of COVID-19 infection with pregnancy outcomes among women who used assisted reproductive technology. Compared with natural conception, assisted reproductive technology was associated with an increased risk of preeclampsia (RR 1.43; 95% CI 1.21-1.68), preterm birth (RR 2.07; 95% CI 1.84-2.33), and low birth weight (RR 1.94; 95% CI 1.72-2.20) during the pandemic. However, the same risks were also present before the pandemic. Compared with no infection, COVID-19 infection was not associated with adverse outcomes among women who conceived with assisted reproductive technology. This study suggests that the COVID-19 pandemic did not significantly impact the pregnancy outcomes of women who underwent assisted reproductive procedures in Quebec. The findings are reassuring for patients concerned about the potential reproductive effects of the pandemic.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3334-3342"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avanafil Mitigates Testicular Ischemia/Reperfusion Injury via NLRP3 Pathway Modulation in Rats.","authors":"Muhammet Celik, Pelin Aydin, Maide Sena Civelek, Nurullah Akgun, Zeynep Karakoy, Cihad Ozcelik, Gulcin Tanriverdiyeva, Erdem Toktay","doi":"10.1007/s43032-024-01696-4","DOIUrl":"10.1007/s43032-024-01696-4","url":null,"abstract":"<p><strong>Objective: </strong>In our study, the effectiveness of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on testicular torsion (TT) related ischemia/reperfusion injury via NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), which triggers inflammatory response, are studied molecularly, biochemically and histopathologically.</p><p><strong>Material and method: </strong>This study was performed on 24 male Wistar albino rats randomized into four groups. Testicular ischemia/reperfusion (I/R) model was created for groups 2, 3 and 4. Groups 3 and 4, respectively, were administered a dose of 5 and 10 mg/kg avanafil before reperfusion by gavage. The testicles which were left in ischemia for two hours, were detorsioned for four hours. All animals were sacrificed after reperfusion. Testicular tissues were examined molecularly, biochemically and histopathologically.</p><p><strong>Results: </strong>The NLRP3, Interleukin-1β (IL-1β) and Tumor Necrosis alpha (TNF-α) mRNA expression levels were observed to be significantly increased in the I/R group compared to the healthy group (p < 0.001). After both doses of avanafil, NLRP3, IL-1β and TNF-α mRNA expression levels, which increased as a result of I/R, decreased in both avanafil groups. (p < 0.001). The greatest decrease was seen at the dose of 10 mg/kg (p < 0.001). Increased Malondialdehyde (MDA) levels due to I/R were statistically significantly decreased in both doses of avanafil (p < 0.001). Decreased Superoxide Dismutase (SOD) levels due to I/R damage increased statistically significantly in both doses of avanafil (p < 0.001).</p><p><strong>Conclusion: </strong>It was found that avanafil can reduce the damage caused by testicular I/R and that it will find new applications in the future with the support of advanced experimental and clinical studies.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3391-3399"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Amniotic Fluid Ureaplasma Species from Pregnancies Complicated by Preterm Prelabor Rupture of Membranes.","authors":"Antonin Libra, Radka Bolehovska, Rudolf Kukla, Ivana Musilova, Ramkumar Menon, Bo Jacobsson, Marian Kacerovsky","doi":"10.1007/s43032-024-01697-3","DOIUrl":"10.1007/s43032-024-01697-3","url":null,"abstract":"<p><p>The main aim of this study was to determine expanded sequence types (eSTs) of Ureaplasma species (U. spp.). DNA isolated from the amniotic fluid of pregnancies complicated by preterm prelabor rupture of membranes (PPROM) using an expanded multilocus sequence typing scheme. Additionally, the study sought to examine whether phylogenetic subgroups of U. spp. DNA differ with respect to maternal demographic and clinical parameters and selected aspects of short-term neonatal morbidity. This retrospective cohort study was focused on singleton pregnancies complicated by PPROM occurring between the gestational ages of 24+0 and 36+6 weeks, where amniocentesis was conducted to assess the intra-amniotic environment and the presence of U. spp. DNA in the amniotic fluid samples was confirmed. The stored aliquots of U. spp. DNA were used to assess differences in nucleotide sequences in six U. spp. genes (ftsH, rpL22, valS, thrS,ureG, and mba-np1) using the eMLST scheme. The expanded multilocus sequence typing scheme was performed in 73 samples of U. spp. DNA isolated from pregnancies complicated by PPROM. In total, 33 different U. spp. DNA eSTs were revealed, 21 (#20, 233-244, 248-251, 253, 255, 259, and 262) of which were novel. The most frequently identified eST was #41, identified in 18% (13/73) of the aliquots. Based on their genetic relationships, the U. spp. DNA was divided into two clusters and four subgroups [cluster I (U. parvum): A, 43% (n = 31); B, 15% (n = 11); and C, 26% (n = 19); cluster II (U. urealyticum): 1; 16% (n = 12)]. Cluster II had a higher rate of polymicrobial findings than cluster I (58% vs 16%; p = 0.005), while subgroup A had the highest rate of concomitant Mycoplasma hominis in the amniotic fluid samples (66%; p = 0.04). In conclusion, Ureaplasma spp. DNA obtained from PPROM consisted of 33 different eSTs of U. spp. DNA. No differences in maternal and neonatal characteristics were found among the phylogenetical subgroups of U. spp. DNA, except for a higher rate of polymicrobial amniotic fluid findings in those with U. urealyticumand the concomitant presence of M. hominis in the amniotic fluid in those with the presence of U. parvum.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3440-3451"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinoic Acid Regulates Spermiogenesis Via Hoxb1 and Shh Signaling in Testicular Germ Cells.","authors":"Saini Pallavi, Simran Jain, Sujit Kumar Mohanty, Syed Waseem Andrabi, Singh Rajender","doi":"10.1007/s43032-024-01648-y","DOIUrl":"10.1007/s43032-024-01648-y","url":null,"abstract":"<p><p>Retinoic acid (RA) regulates all four major events in spermatogenesis; spermatogonial differentiation, meiotic entry, spermiogenesis, and spermiation. For the pre-meiotic phase, Sertoli cells are the source of RA and for the post-meiotic phase, pachytene spermatocytes are the source of RA. While the entire spermatogenic process is regulated by RA, how each of these phases is regulated by RA remains completely unknown. Homeobox B1 (Hoxb1) has two retinoic acid response elements (RARE) upstream and downstream of the gene. In this study, we investigated if RA facilitates spermatogenesis by its action on Hoxb1. The expressions of the Hoxb1 and Sonic hedgehog (Shh) genes were analyzed in the post-natal mouse testes and the testicular localizations of Hoxb1, Shh and Gli1 were analyzed by immunohistochemistry in the adult rat testis. To delineate the signaling mechanisms, Hoxb1 expression was altered in vitro and in vivo using retinoic acid and miR-361-3p. Finally, the levels of miR-361-3p and HOXB1 were analyzed in infertile human sperm samples. Hoxb1 and Shh gene expressions were found to be low in the testis of post-natal Swiss mice of 7, 14, 28, 35, and 60 days, after which the expressions of both spiked. Immunohistochemistry in the adult mouse testis showed the expressions of Hoxb1, Shh, and Gli1 in the elongating spermatids. Exposure of GC2 cells to RA and in vivo IP RA injection upregulated Hoxb1 and Shh signaling in the testis with increased expressions of Shh, Gli1, and Hdac1. Retinoic acid administration in Swiss mice compromised sperm production and reduced epididymal sperm count. The analysis of infertile human semen samples revealed an increased level of HOXB1 and a decreased level of miR-361-3p as compared to fertile controls. We conclude that retinoic acid regulates late stage of spermatogenesis (spermiogenesis) by affecting Hoxb1 and Shh signaling.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"3400-3412"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}