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19 pages, 14791 KiB

Open AccessArticle

Assessing the Efficacy of Acanthoic Acid Isolated from Acanthopanax koreanum Nakai in Male Infertility: An In Vivo and In Silico Approach

by Nguyen Viet Phong, Hyo-Sung Kim, Hyun-Jung Park, Eunbyul Yeom and Seo Young Yang

Curr. Issues Mol. Biol. 2024, 46(7), 7411-7429; https://doi.org/10.3390/cimb46070440 - 13 Jul 2024

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Abstract

Acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum Nakai, possesses diverse pharmacological activities, including anti-inflammatory, anti-diabetic, gastrointestinal protection, and cardiovascular protection. This study is the first to investigate the egg-hatching rates of Drosophila melanogaster affected by acanthoic acid. Notably, [...] Read more.

Acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum Nakai, possesses diverse pharmacological activities, including anti-inflammatory, anti-diabetic, gastrointestinal protection, and cardiovascular protection. This study is the first to investigate the egg-hatching rates of Drosophila melanogaster affected by acanthoic acid. Notably, male flies supplemented with 10 μM acanthoic acid exhibited a strong increase in hatching rates compared with controls under adverse temperature conditions, suggesting a potential protective effect against environmental stressors. Molecular docking simulations revealed the binding affinities and specific interactions between acanthoic acid and proteins related to male infertility, including SHBG, ADAM17, and DNase I, with binding affinity values of −10.2, −6.8, and −5.8 kcal/mol, respectively. Following the docking studies, molecular dynamic simulations were conducted for a duration of 100 ns to examine the stability of these interactions. Additionally, a total binding energy analysis and decomposition analysis offered insights into the underlying energetic components and identified key contributing residues. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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11 pages, 569 KiB

Open AccessArticle

Genetic Insights into Azoospermia and Severe Oligozoospermia: Discovering Seven SNPs through GWAS and In Silico Analysis

by Alexia Chatziparasidou, Maria-Anna Kyrgiafini, Theologia Sarafidou, Katerina A. Moutou and Zissis Mamuris

Curr. Issues Mol. Biol. 2024, 46(7), 6522-6532; https://doi.org/10.3390/cimb46070389 - 27 Jun 2024

Cited by 1 | Viewed by 1198

Abstract

Azoospermia and severe oligozoospermia represent the most extreme forms of male infertility. Despite their prevalence, the genetic foundations of these conditions are not well understood, with only a limited number of genetic factors identified so far. This study aimed to identify single-nucleotide polymorphisms [...] Read more.

Azoospermia and severe oligozoospermia represent the most extreme forms of male infertility. Despite their prevalence, the genetic foundations of these conditions are not well understood, with only a limited number of genetic factors identified so far. This study aimed to identify single-nucleotide polymorphisms (SNPs) linked to both azoospermia and severe oligozoospermia. We conducted a genome-wide association study (GWAS) involving 280 Greek males with normal semen parameters and 85 Greek males diagnosed with either azoospermia or severe oligozoospermia. Following rigorous quality control measures, our analysis identified seven SNPs associated with azoospermia/severe oligozoospermia. An in silico functional annotation was subsequently used to further investigate their role. These SNPs, found in regions not previously associated with male reproductive disorders, suggest novel genetic pathways that may contribute to these forms of infertility and pave the way for future studies. Additionally, this study sheds light on the significant role of noncoding RNAs in the pathogenesis of male infertility, with three of the identified SNPs situated in long intergenic non-coding RNAs (lincRNAs). Our findings highlight the intricate genetic landscape of azoospermia and severe oligozoospermia, underlining the necessity for more detailed studies to fully grasp the underlying mechanisms and their potential for informing diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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11 pages, 1508 KiB

Open AccessArticle

Follow-Up Study of 17-β Estradiol, Prolactin and Progesterone with the Kinetics and Prevalence of T. gondii Infection in Pregnant Women

by Yithzel Guadalupe Luna Rojas, Eva Elizabet Camarena Pulido, Laura Rocío Rodríguez-Pérez and María de la Luz Galván-Ramírez

Curr. Issues Mol. Biol. 2024, 46(6), 5701-5711; https://doi.org/10.3390/cimb46060341 - 7 Jun 2024

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Abstract

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world’s population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In [...] Read more.

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world’s population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-β estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies’ kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-β estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-β estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-β estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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17 pages, 13213 KiB

Open AccessArticle

Combining RNAscope, Immunohistochemistry (IHC) and Digital Image Analysis to Assess Podoplanin (PDPN) Protein and PDPN_mRNA Expression on Formalin-Fixed Paraffin-Embedded Normal Human Placenta Tissues

by Larisa Cristina Tomescu, Andrei Alexandru Cosma, Mihaela Pasca Fenesan, Eugen Melnic, Vergil Petrovici, Simona Sarb, Monica Chis, Ioan Sas, Domenico Ribatti, Anca Maria Cimpean and Florica Ramona Dorobantu

Curr. Issues Mol. Biol. 2024, 46(6), 5161-5177; https://doi.org/10.3390/cimb46060310 - 24 May 2024

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Abstract

The expression and function of podoplanin (PDPN) in the normal human placenta has been debated in placental evaluation. This study emphasizes the importance of a multimodal approach of PDPN expression in normal human placentas. A complete examination is performed using immunohistochemistry, RNAscope and [...] Read more.

The expression and function of podoplanin (PDPN) in the normal human placenta has been debated in placental evaluation. This study emphasizes the importance of a multimodal approach of PDPN expression in normal human placentas. A complete examination is performed using immunohistochemistry, RNAscope and automated Digital Image examination (DIA) interpretation. QuPath DIA-based analysis automatically generated the stromal and histological scores of PDPN expression for immunohistochemistry and RNAscope stains. The umbilical cord’s isolated fibroblasts and luminal structures expressed PDPN protein and PDPN_mRNA. RNAscope detected PDPN_mRNA upregulation in syncytial placental knots trophoblastic cells, but immunohistochemistry did not certify this at the protein level. The study found a significant correlation between the IHC and RNAscope H-Score (p = 0.033) and Allred Score (p = 0.05). A successful multimodal strategy for PDPN assessment in human placentas confirmed PDPN expression heterogeneity in the full-term human normal placenta and umbilical cord at the protein and mRNA level. In placental syncytial knots trophoblastic cells, PDPN showed mRNA overexpression, suggesting a potential role in placenta maturation. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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14 pages, 3905 KiB

Open AccessArticle

The Ggcx^K325Q Mutation Does Not Affect the Calcium Homeostasis of the Epididymis and Male Fertility in Mice

by Mingxiang Xiong, Pang Cheng, Bo Liu, Yanqiu Zhao, Ting Gao and Zhen Li

Curr. Issues Mol. Biol. 2024, 46(6), 5052-5065; https://doi.org/10.3390/cimb46060303 - 22 May 2024

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Abstract

A low-calcium microenvironment is imperative for spermatozoa maturation within the epididymis. Our previous work has shown that γ-glutamyl carboxylase (GGCX), the carboxylation enzyme of the matrix Gla protein (MGP), plays an essential role in epididymal calcium homeostasis and sperm maturation in rats and [...] Read more.

A low-calcium microenvironment is imperative for spermatozoa maturation within the epididymis. Our previous work has shown that γ-glutamyl carboxylase (GGCX), the carboxylation enzyme of the matrix Gla protein (MGP), plays an essential role in epididymal calcium homeostasis and sperm maturation in rats and that the GGCX SNP mutation rs699664 was associated with asthenozoospermia (AZS) in humans. Here, we investigated the expression patterns of GGCX and MGP in the mouse epididymis and generated Ggcx^K325Q knock-in (KI) mice. We also tested the effects of this mutation on epididymal calcium homeostasis, sperm function, and male fertility in Ggcx^K325Q−/− mice. The results showed that both GGCX and MGP were enriched in all regions of the mouse epididymis, especially in the initial segment of the epididymis. Double immunofluorescence staining revealed that GGCX colocalized with MGP in the epithelial cells of the initial segment and caput regions as well as in the lumen of the corpus and cauda regions of the mouse epididymis. However, the Ggcx^K325Q−/− mice were fertile with normal epididymal morphology, sperm functions, and epididymal calcium concentration. Overall, our findings revealed that the Ggcx^K325Q mutation does not exert any discernible effect on male fertility in mice. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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16 pages, 2785 KiB

Open AccessArticle

Association between KRAS and PIK3CA Mutations and Progesterone Resistance in Endometriotic Epithelial Cell Line

by Kosuke Kanno, Kentaro Nakayama, Sultana Razia, Sohel Hasibul Islam, Zahan Umme Farzana, Shahataj Begum Sonia, Hitomi Yamashita, Masako Ishikawa, Tomoka Ishibashi, Kayo Imamura, Tohru Kiyono and Satoru Kyo

Curr. Issues Mol. Biol. 2024, 46(4), 3579-3594; https://doi.org/10.3390/cimb46040224 - 19 Apr 2024

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Abstract

Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations [...] Read more.

Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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10 pages, 1591 KiB

Open AccessCommunication

Frequency of Gene Polymorphisms in Admixed Venezuelan Women with Recurrent Pregnancy Loss: Microsomal Epoxy Hydroxylase (rs1051740) and Enos (rs1799983)

by María Johanna Peña, Claudia Valentina De Sanctis, Juan Bautista De Sanctis and Jenny Valentina Garmendia

Curr. Issues Mol. Biol. 2024, 46(4), 3460-3469; https://doi.org/10.3390/cimb46040217 - 17 Apr 2024

Cited by 1 | Viewed by 1361

Abstract

Recurrent pregnancy loss (RPL) affects around 2% of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, [...] Read more.

Recurrent pregnancy loss (RPL) affects around 2% of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene single nucleotide polymorphisms (SNPs) have been associated with RPL. The frequency of some SNPs is increased in women suffering from RLP from Asian or Caucasian races; however, in admixed populations, the information on possible genetic links is scarce and contradictory. This study aimed to assess the frequency of two SNPs present in two different enzymes involved in medical conditions observed during pregnancy. It is a case–control study. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics, is present in the ovaries, and is hormonally regulated. The endothelial nitric oxide synthase (NOS3) that forms nitric is involved in vascular tone. Two SNPs, rs1051740 (mEPH) and rs1799983 (NOS3), were assessed. The study included 50 controls and 63 primary RPL patients. The frequency of mutated alleles in both SNPs was significantly higher in patients (p < 0.05). Double-mutated homozygotes were encountered only in RPL patients (p < 0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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19 pages, 85340 KiB

Open AccessArticle

Unveiling the Ovarian Cell Characteristics and Molecular Mechanism of Prolificacy in Goats via Single-Nucleus Transcriptomics Data Analysis

by Sanbao Zhang, Yirong Wei, Xiaotong Gao, Ying Song, Yanna Huang and Qinyang Jiang

Curr. Issues Mol. Biol. 2024, 46(3), 2301-2319; https://doi.org/10.3390/cimb46030147 - 11 Mar 2024

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Abstract

Increases in litter size, which are influenced by ovulation, are responsible for between 74% and 96% of the economic value of genetic progress, which influences selection. For the selection and breeding of highly prolific goats, genetic mechanisms underlying variations in litter size should [...] Read more.

Increases in litter size, which are influenced by ovulation, are responsible for between 74% and 96% of the economic value of genetic progress, which influences selection. For the selection and breeding of highly prolific goats, genetic mechanisms underlying variations in litter size should be elucidated. Here, we used single-nucleus RNA sequencing to analyze 44,605 single nuclei from the ovaries of polytocous and monotocous goats during the follicular phase. Utilizing known reference marker genes, we identified 10 ovarian cell types characterized by distinct gene expression profiles, transcription factor networks, and reciprocal interaction signatures. An in-depth analysis of the granulosa cells revealed three subtypes exhibiting distinct gene expression patterns and dynamic regulatory mechanisms. Further investigation of cell-type-specific prolificacy-associated transcriptional changes elucidated that “downregulation of apoptosis”, “increased anabolism”, and “upstream responsiveness to hormonal stimulation” are associated with prolificacy. This study provides a comprehensive understanding of the cell-type-specific mechanisms and regulatory networks in the goat ovary, providing insights into the molecular mechanisms underlying goat prolificacy. These findings establish a vital foundation for furthering understanding of the molecular mechanisms governing folliculogenesis and for improving the litter size in goats via molecular design breeding. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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