Systems Biology in Reproductive Medicine最新文献

{"title":"High throughput deep proteomic analysis of seminal plasma from stallions with contrasting semen quality","authors":"T. Talluri, A. Kumaresan, N. Paul, M. Sinha, John Peter Ebenezer Samuel King, K. Elango, Ankur Sharma, Kathan Raval, R. Legha, Y. Pal","doi":"10.1080/19396368.2022.2057257","DOIUrl":"https://doi.org/10.1080/19396368.2022.2057257","url":null,"abstract":"Abstract Seminal plasma proteins and pathways associated with sperm motility have not been elucidated in stallions. Therefore, in the current study, using the high throughput LC/MS-MS approach, we profiled stallion seminal plasma proteins and identified the proteins and pathways associated with sperm motility. Seminal plasma from six stallions producing semen with contrasting sperm motility (n = 3 each high-and low-motile group) was utilized for proteomic analysis. We identified a total of 1687 proteins in stallion seminal plasma, of which 1627 and 1496 proteins were expressed in high- (HM) and low- motile (LM) sperm of stallions, respectively. A total number of 1436 proteins were co-expressed in both the groups; 191 (11%) and 60 (3.5%) proteins were exclusively detected in HM and LM groups, respectively. A total of 220 proteins were upregulated (>1-fold change) and 386 proteins were downregulated in SP from LM group stallions as compared to HM group stallions, while 830 proteins were neutrally expressed in both the groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed dysregulation of the important proteins related to mitochondrial function, acrosome, and sperm cytoskeleton in the seminal plasma of stallions producing ejaculates with low sperm motility. High abundance of peroxiredoxins and low abundance of seminal Chaperonin Containing TCP1 Complex (CCT) complex and Annexins indicate dysregulated oxidative metabolism, which might be the underlying etiology for poor sperm motility in LM group stallions. In conclusion, the current study identified the seminal plasma proteomic alterations associated with poor sperm motility in stallions; the results indicate that poor sperm motility in stallions could be associated with altered expression of seminal plasma proteins involved in oxidative metabolism.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41247287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of preovulatory estradiol concentrations on subsequent luteal function in beef cattle","authors":"M. K. McLean, T. Geary, A. Zezeski, M. Smith, T. Spencer, K. Pohler, S. Reese, G. Perry","doi":"10.1080/19396368.2022.2038717","DOIUrl":"https://doi.org/10.1080/19396368.2022.2038717","url":null,"abstract":"Abstract It has been hypothesized that circulating concentrations of estradiol during the preovulatory period, can impact subsequent progesterone concentrations. Ovulation was synchronized in nonlactating beef cows (n = 53). Cows that exhibited estrus before gonadotrophin-releasing hormone (GnRH)-induced ovulation (d 0) had greater (p<.01) peak concentrations of estradiol compared with cows that did not express estrus (11.5 ± 0.8 vs. 6.2 ± 0.6 pg/mL), respectively, but there was no difference in ovulatory follicle size (p= .80) or interval from GnRH2 to ovulation (p=.23). Circulating concentrations of progesterone during luteal formation (d 3–7; p=.70 and p=.77) or mid-luteal phase (d 8–14; p=.39 and p=.12) were not affected by elevated periovulatory estradiol or an interaction with day. To investigate the direct influence of estradiol on luteal function, ovulation (d 0) was synchronized in nonlactating beef cows and cows were allocated to three groups (control, n = 5; vehicle injection, n = 4; or an estradiol antagonist (Fulvestrant; ICI 182,780), n = 4. Intrafollicular injection of vehicle (100 µL) or an estradiol antagonist (25 μg Fulvestrant in 100 µL) into the largest follicle occurred on d –2. Concentrations of estradiol increased (p<.0001) from d –2 to 0 but did not differ among groups (p>.50). Furthermore, plasma concentrations of progesterone on d 0 through 20 were not affected by treatment (p=.86). These results indicate that elevated preovulatory estradiol before ovulation was not required to prepare granulosa cells for luteinization or subsequent luteal progesterone secretion but did tend to impact luteal lifespan.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43737967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic reprogramming in cloned mouse embryos following treatment with DNA methyltransferase and histone deacetylase inhibitors","authors":"Maryam Zarei, Boshra Shamaghdari, Zeinab Vahabi, A. Dalman, P. Eftekhari Yazdi","doi":"10.1080/19396368.2022.2036868","DOIUrl":"https://doi.org/10.1080/19396368.2022.2036868","url":null,"abstract":"Abstract We examined the effects of DNA methyltransferase inhibitor – RG108, and histone deacetylase inhibitor – SAHA, on the reprogramming parameters of cloned mouse embryos produced by somatic cell nuclear transfer into oocytes. The programming parameters studied included dynamics of histone reacetylation, developmental rate, DNA methylation, and transcript levels of genes, all of which are pivotal to lineage specification and blastocyst formation. At the pronuclear stage, somatic nucleus-transplanted oocytes treated with 5 µM SAHA presented higher histone acetylation at H3K9, H3K14, H4K16 and H4K12, compared to untreated clones (p < 0.05). At the morula stage, cloned embryos treated with 5 μM RG108 or 5 μM SAHA presented lower DNA methylation intensity compared to untreated clones (p < 0.05), resembling the intensity levels of fertilized embryos. However, these effects were not observed when RG108 and SAHA were used in combination. The rate of morula formation was significantly higher in cloned embryos treated with 5 µM SAHA than in untreated clones, whereas treatment with RG108 resulted in no obvious effects on morula formation rates. On the other hand, the combined treatment with RG108 and SAHA resulted in inferior rates of cloned morula formation, compared to untreated clones. At the blastocyst stage, the aberrant expression levels of key developmental genes Oct4 and Cdx2, but not Nanog, were corrected in cloned embryos by the treatment with RG108. This is similar to the intensity levels seen in fertilized embryos. The expression of Rpl7l1 gene was significantly higher in embryos treated with both RG108 and SAHA than in untreated and in control groups. In summary, the present study showed that SAHA and RG108, when applied separately, improve the rate and quality of cloned mouse embryos.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42659812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioethics in human embryology: the double-edged sword of embryo research","authors":"G. Anifandis, P. Sutovsky, P. Turek, S. Chavez, T. Kunej, C. Messini, S. Schon, A. Mavroforou, E. Adashi, S. Krawetz","doi":"10.1080/19396368.2022.2052771","DOIUrl":"https://doi.org/10.1080/19396368.2022.2052771","url":null,"abstract":"Abstract There has been a significant increase in the use of assisted reproductive therapies (ARTs) over the past several decades, allowing many couples with infertility to conceive. Despite the achievements in this field, a mounting body of evidence concerning the epigenetic risks associated with ART interventions such as ovarian hormonal stimulation, intracytoplasmic sperm injection (ICSI), and in vitro culture (IVC) of oocytes and embryos has also emerged. Induced development of multiple follicles, the IVC media itself, and extended culture may alter the epigenome of both gametes and embryos, resulting in yet to be fully understood developmental, postnatal, and adult life health consequences. Investigators have attempted to decipher the molecular mechanisms mediating ART-induced epigenetic changes using either human samples or animal models with some success. As research in this field continues to expand, the ethical responsibilities of embryologists and researchers have become critically important. Here, we briefly discuss the ethical aspects of ART research, concentrating on the constraints arising from the perceived 'unnaturalness' of many of these procedures. Secondly, we focus on the bioethics and morality of human embryo research in general and how ethically acceptable model systems may be used to mimic early human embryogenesis. Lastly, we review the 14-day culture limit of human embryos and the notion that this rule could be considered of taken into account using new technologies and cues from animal models. The ‘black box’ of early post-implantation embryogenesis might be revealed using embryo models. As long as this distinct moral line has been drawn and closely followed, we should not fear scientific growth in embryo research. Although in vitro fertilization (IVF) is ethically acceptable, research with human embryos to improve its success raises serious ethical concerns that are in need of constant revisiting. Glossary index: Moral status: the ascription of obligations and rights to embryos on the basis of sentience; Sentience: the capacity of the developing embryo to experience feelings and sensations, such as the awareness of pain; Ectogenesis: the growth of the embryo in an artificial environment outside the mother's body.","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42319531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The vitrification system may affect preterm and cesarean delivery rates after single vitrified blastocyst transfer.","authors":"Yunhong Lin,&nbsp;Lincui Da,&nbsp;Shengrong Du,&nbsp;Qingfen Chen,&nbsp;Suzhu Chen,&nbsp;Beihong Zheng","doi":"10.1080/19396368.2021.2005717","DOIUrl":"https://doi.org/10.1080/19396368.2021.2005717","url":null,"abstract":"<p><p>The purpose of this study was to investigate the possible effects of different vitrification systems on single vitrified blastocyst transfer cycles. The clinical and birth outcomes of 412 patients who underwent single vitrified blastocyst transfer between January 2018 and June 2020 were retrospectively analyzed and compared between patients who underwent blastocyst vitrification with kit A (group A, 196 patients) and those who underwent blastocyst vitrification with kit B (group B, 216 patients). Clinical outcomes, including the clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate, late miscarriage rate, ectopic pregnancy rate, twin pregnancy rate, and induced labor rate due to fetal malformation, were not significantly different between the two groups (P > 0.05). The preterm delivery rate among singleton newborns (11.57% vs. 3.23%, P < 0.05) and the cesarean delivery rate were significantly higher in group B than in group A (70.25% vs. 57.26%, P < 0.05). Birth outcomes, including the male-to-female ratio, low-birth-weight rate, macrosomia rate, birth defect rate, newborn gestational age, neonatal body weight, and singleton neonatal body length, were not significantly different (P > 0.05). Our findings suggest that different vitrification systems might differentially affect birth outcomes. Such disparity could reflect differences in kit composition and/or protocol.<b>ABBREVIATIONS</b>: DMSO: dimethyl sulfoxide; ES: equilibration solution; VS: vitrification solution; BMI: body mass index; ICSI: intracytoplasmic sperm injection; OR: odds ratio; CI: confidence interval.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39709711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the role of thiol / disulfide homeostasis in the etiology of idiopathic male infertility with a novel and automated assay.","authors":"Uygar Micoogullari,&nbsp;Mehmet Caglar Cakici,&nbsp;Furkan Umut Kilic,&nbsp;Erdem Kisa,&nbsp;Burak Ozcift,&nbsp;Alper Caglayan,&nbsp;Salim Neselioglu,&nbsp;Omer Faruk Karatas,&nbsp;Ozcan Erel","doi":"10.1080/19396368.2021.2003481","DOIUrl":"https://doi.org/10.1080/19396368.2021.2003481","url":null,"abstract":"<p><p>Idiopathic male infertility (IMI) is the absence of a reason to explain a patient's infertility, and it occurs at a frequency of %31. In this study we aimed to investigate the oxidant/antioxidant status of patients with IMI and compare their results to those of healthy controls.A total of 79 patients with IMI (group 1) and 90 healthy individuals (group 2) were included in the study. We used Erel & Neşelioğlu's thiol/disulfide homeostasis test. Collective and individual measurements of oxidative/antioxidative balance components were carried out by this novel thiol/disulfide homeostasis test. Serum antioxidant (total thiol (toSH), native thiol (SH)) and oxidant (disulfide (SS)) levels of all study participants were measured. The results from both groups were compared and analyzed statistically. After toSH, SH, and SS levels were determined, SS/toSH% and SS/SH% levels for each group were analyzed separately and compared statistically.The toSH, SH levels, and SS/SH%, SS/toSH% ratios were significantly different between the groups (p < 0.05).While antioxidant parameters (toSH and SH values) decreased in group1, oxidant parameters (SS/SH%, SS/toSH%) increased significantly. Although SS values were higher in group 1, the difference was not significant (p = 0.214). The SH cutoff value of 507.15 µmol/L predicted the probability of IMI development with 72.2% sensitivity and 74.4% specificity and toSH cutoff value of 545.45 µmol/L predicted IMI development with 70.9% sensitivity and 73.3 specificity (p < 0.001). Multivariate logistic regression analysis showed that the only independent risk factor for the development of IMI is SH. Patients with IMI had a significant change in their thiol/disulfide homeostasis, which suggests the involvement of this imbalance in the pathophysiology of IMI. Furthermore, these results also support the notion of the involvement of oxidative stress in sperm dysfunction. It also points to the possibility of using antioxidants in IMI treatment.<b>Abbreviations:</b> IMI: idiopathic male infertility; toSH: total thiol; SH: native thiol; SS: disulfide; OS: oxidative stress; ROS: reactive oxygen species; DCF: dichlorofluorescein; MiOXSYS: male infertility oxidative system; MOSI: male oxidative stress infertility; LC: L-carnitine; LAC: L-acetylcarnitine; Vit: vitamin; OAT: oligoasthenozoospermia; TMSC: total motile sperm count; WHO: World Health Organization; BMI: body mass index; DTNB: 5,5'-dithiobis-2-nitrobenzoic acid; CV: coefficient variation; ROC: receiver operating characteristic; PR: progressive, NP: non-progressive.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant and anti-inflammatory protective effects of rutin and kolaviron against busulfan-induced testicular injuries in rats.","authors":"Sunny O Abarikwu,&nbsp;Rex-Clovis C Njoku,&nbsp;Ifeoma G John,&nbsp;Benjamin A Amadi,&nbsp;Chidimma J Mgbudom-Okah,&nbsp;Chigozie L Onuah","doi":"10.1080/19396368.2021.1989727","DOIUrl":"https://doi.org/10.1080/19396368.2021.1989727","url":null,"abstract":"<p><p>There are few treatment options, including the use of natural phenolics-based combination therapy for mitigating male infertility conditions associated with chemotherapy. Busulfan is an anti-cancer drug that leads to testicular problems in humans. Here, we studied the effect of co-treatment of rutin and kolaviron against busulfan-induced testis damage. Young adult male Wistar rats were intraperitoneally injected busulfan (4 mg/kg b.w), and then orally administered rutin (30 mg/kg b.w), and kolaviron (50 mg/kg b.w) alone and combined for 60 days. Results revealed that rutin and kolaviron alone or in combination reversed busulfan-induced increase in oxidative stress along with sperm quality of treated animals. However, kolaviron and rutin separately improved the concentrations of MDA and GSH and sperm quality more than when they were combined. Similarly, rutin and kolaviron separately or in combination preserved spermatogenesis and relieved busulfan-induced increase in nitric oxide concentration, myeloperoxidase and 3β-hydroxysteroid dehydrogenase activities. Co-supplementation with kolaviron but not rutin nor when rutin was combined with kolaviron also improved the testicular level of tumor necrosis-alpha. Finally, the histological features in the testes caused by busulfan were reversed by rutin, whereas treatment with kolaviron alone or in combination with rutin partially protected the testis from busulfan-induced injury as demonstrated by the appearance of few germ cells, damaged tubules, loss of round spermatids and defoliation of the seminiferous epithelium. Thus, the combined treatment regimen of rutin and kolaviron sparingly prevented busulfan-induced testicular injuries in rats.<b>Abbreviations:</b> CAT: Catalase; GSH: Glutathione; 3β-HSD: 3β- hydroxysteroid Dehydrogenase; MDA: Malondialdehyde; TNF-α: Tumor necrosis-alpha; BUS: Busulfan; RUT: Rutin; KV: Kolaviron; TBARS: Thiobarbituric Acid Reactive Substances; MPO: Myeloperoxidase; ELISA: Enzyme-Linked Immunoassay; NAD: Nicotinamide Adenine Dinucleotide (oxidized); ROS: Reactive Oxygen Species.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39603813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein affects gonadotrophin-releasing hormone secretion in GT1-7 cells via modulating kisspeptin receptor and key regulators.","authors":"Jingyuan Xiong,&nbsp;Ye Tian,&nbsp;Aru Ling,&nbsp;Zhenmi Liu,&nbsp;Li Zhao,&nbsp;Guo Cheng","doi":"10.1080/19396368.2021.2003910","DOIUrl":"https://doi.org/10.1080/19396368.2021.2003910","url":null,"abstract":"<p><p>Epidemiological studies have shown that genistein, an isoflavonoid phytoestrogen from soybean, affects endocrine and reproductive systems and alters pubertal onset. Administration of genistein in mice could impact the electrophysiology of hypothalamic neurons associated with the secretion of gonadotropin-releasing hormone (GnRH), a key component of hypothalamic-pituitary-gonadal (HPG) axis that governs hormone release and reproductive maturation. However, whether genistein could directly influence GnRH secretion in GnRH-specific neurons requires further investigation. Here, mouse hypothalamic GT1-7 neurons were recruited as a GnRH-expressing model to directly evaluate the effect and mechanisms of genistein on GnRH release. Results from this study demonstrated that genistein treatment decreased cell viability, impacted cell cycle distribution, and induced apoptosis of GT1-7 cells. A high concentration of genistein (20 μM) significantly increased GnRH secretion by 122.4% compared to the control. Since GnRH release is regulated by components of the kisspeptin-neurokinin-dynorphin (KNDy) system and regulators including SIRT1, PKC_γ, and MKRN3, their transcription and translation were examined. Significant increases were observed for the mRNA and protein levels of the KNDy component kisspeptin receptor (<i>Gpr54</i>/Kissr). Compared to the control, genistein treatment upregulated the level of <i>Sirt1</i> mRNA level, while it downregulated <i>Prkcg</i> and <i>Mkrn3</i> expression. Therefore, this study provided direct evidence that genistein treatment could affect GnRH secretion by modulating kisspeptin receptors, SIRT1, PKC_γ and MKRN3 in GT1-7 cells.<b>Abbreviations:</b> GnRH: gonadotropin-releasing hormone; HPG: hypothalamic-pituitary-gonadal; KNDy: kisspeptin-neurokinin-dynorphin; LH: luteinizing hormone; FSH: follicle-stimulating hormone; ARC: arcuate nucleus; ER: estrogen receptor; SIRT1: silent information regulator 1; PKCγ: protein kinase c γ: MKRN3: makorin ring finger protein 3; LC: lethal concentration; PI: propidium iodide; ECL: chemiluminescence; BCA: bicinchoninic acid assay; PBS: phosphate-buffered saline; CT: fluorescence reached threshold; PVDF: polyvinylidene difluoride.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39787034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FSHR antagonists can trigger a PCOS-like state.","authors":"Faiza Hanif Waghu,&nbsp;Karishma Desai,&nbsp;Sumana Srinivasan,&nbsp;Kaushiki S Prabhudesai,&nbsp;Vikas Dighe,&nbsp;Kareenhalli V Venkatesh,&nbsp;Susan Idicula-Thomas","doi":"10.1080/19396368.2021.2010837","DOIUrl":"https://doi.org/10.1080/19396368.2021.2010837","url":null,"abstract":"<p><p>Over the recent years, FSHR has become an important target for development of fertility regulating agents, as impairment of FSH-FSHR interaction can lead to subfertility or infertility. In our previous study, we identified a 9-mer peptide (FSHβ (89-97)) that exhibited FSHR antagonist activity. The histopathological and biochemical observations indicated, in addition to FSHR antagonism, a striking resemblance to a PCOS-like state. These observations led us to hypothesize that use of FSHR antagonists can trigger a PCOS-like state. In the present study, to validate this hypothesis, we performed qRT-PCR validation using ovarian tissue samples from our previous study. Expression of three genes known to be differentially expressed in PCOS was evaluated and found to be similar to the PCOS state. To further test the hypothesis, theoretical simulations were carried out by using the human menstrual cycle model available in the literature. Model simulations for FSHR antagonism were indicative of increased testosterone levels, increased ratio of luteinizing hormone/follicle stimulating hormone, and stockpiling of secondary follicles, which are typical characteristics of PCOS. The findings of this study will be relevant while reviewing the utility of FSHR antagonists for fertility regulation and reproductive medicine.<b>Abbreviations:</b> FSH: Follicle-stimulating hormone; FSHR: Follicle-stimulating hormone receptor; cAMP: Cyclic adenosine 3'5' monophosphate; PKA: Protein kinase A; PI3K: Phosphoinositide 3-kinase; PKB: protein kinase B; ERK1/2: Extracellular signal-regulated protein kinase 1/2; MAPK: Mitogen-activated protein kinases; T: testosterone; E2: estradiol; PCOS: Polycystic ovarian syndrome; LH: luteinizing hormone; Lhcgr: luteinizing hormone/choriogonadotropin receptor; CYP17A1: cytochrome P450 family 17 subfamily A member 1; Inhba: inhibin subunit beta A; qRT-PCR: Real-Time quantitative reverse transcription polymerase chain reaction; FSHβ: Follicle-stimulating hormone β subunit; Ct: Cycle threshold; Rn18s: Rattus norvegicus 18S ribosomal RNA.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39772912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letrozole promotes the expression of integrin αvβ3 and HOXA10 in endometrium of endometriosis.","authors":"Jing Zhang,&nbsp;Lihui Wang,&nbsp;Chunyan Li,&nbsp;Hui Zhang,&nbsp;Rui Li,&nbsp;Mingjiang Li","doi":"10.1080/19396368.2021.2013577","DOIUrl":"https://doi.org/10.1080/19396368.2021.2013577","url":null,"abstract":"<p><p>Endometriosis is a common estrogen-dependent chronic inflammatory disease that leads to infertility in women of reproductive age. Perhaps infertility reflects the reduced expression of integrin αvβ3 and HOXA10 in endometriosis. Previous studies have shown that administration of letrozole, a non-steroidal aromatase inhibitor for cancer treatment, increased the clinical pregnancy rate in women with endometriosis, but the mechanisms remain to be determined. In this communication, a rat model of endometriosis was established. Animals were treated with letrozole at 2ug/kg of body weight, intragastric administration for 15 consecutive days. Letrozole increased the expression of αvβ3 and HOXA10 in the endometriosis model and endometrial receptivity.<b>Abbreviations:</b> WOI: window of implantation; RGD: Arg-Gly-Asp; HOX: homeobox; E2: estradiol; SPF: specific pathogen-free.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39630380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}