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18 pages, 19397 KiB

Open AccessArticle

Myofibroblast-like Cells and Junctional Complex Development Play a Role in Mouse Pubic Symphysis Remodeling During Pregnancy and Postpartum

by Viviane Souza Rosa, Bianca Gazieri Castelucci, Monica Moreira, Paulo Pinto Joazeiro and Sílvio Roberto Consonni

Int. J. Mol. Sci. 2025, 26(11), 5307; https://doi.org/10.3390/ijms26115307 - 31 May 2025

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Abstract

During mouse pregnancy, the pubic symphysis (PS) undergoes a gradual transitioning into an interpubic ligament (IpL) for a successful delivery. After birth, this IpL is rapidly remodeled, returning to the non-pregnant morphology. The PS fibrocartilaginous cells acquire a myofibroblast-like phenotype, characterized by extracellular [...] Read more.

During mouse pregnancy, the pubic symphysis (PS) undergoes a gradual transitioning into an interpubic ligament (IpL) for a successful delivery. After birth, this IpL is rapidly remodeled, returning to the non-pregnant morphology. The PS fibrocartilaginous cells acquire a myofibroblast-like phenotype, characterized by extracellular matrix (ECM) secretion, expression of α-smooth muscle actin (α-SMA), and vimentin. While the presence of myofibroblast-like cells during the IpL remodeling is well described, cell–cell interactions and how this might contribute to the delivery remains poorly understood. This study uses ultrastructure and molecular approaches to investigate cell–cell and cell–ECM junctions during mouse pregnancy and postpartum. Our findings reveal that the intercellular contacts between adjacent IpL myofibroblast-like cells, particularly at late pregnancy stages, are characterized as adherens and GAP junctions. The acquisition of contractile elements by IpL cells, coupled with neighboring cells and the surrounding ECM via junctional complexes, suggests an important role in supporting changes in the mechanical forces generated by pubic bone movements during mouse pregnancy and also in tying the pelvic bones together, which may help the birth canal closure after delivery. Further studies in PS biology may investigate fibroblast to myofibroblast differentiation signaling cascades, which regulate the expression of pro-fibrotic proteins and may provide new insights for preterm labor. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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15 pages, 1351 KiB

Open AccessArticle

Assessing the Viability of Segmental Aneuploid Embryos: A Chromosomal Concordance Study of 175 Human Blastocysts

by En-Hui Cheng, Hui-Hsin Shih, Tsung-Hsien Lee, Pin-Yao Lin, Tzu-Ning Yu, Chun-Chia Huang, Maw-Sheng Lee and Chun-I Lee

Int. J. Mol. Sci. 2025, 26(11), 5284; https://doi.org/10.3390/ijms26115284 - 30 May 2025

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Abstract

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to select euploid embryos for in vitro fertilization (IVF), but its accuracy in predicting the implantation potential for full segmental aneuploid (Seg-A) embryos remains unclear. In this study, we investigated chromosomal concordance between clinically [...] Read more.

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to select euploid embryos for in vitro fertilization (IVF), but its accuracy in predicting the implantation potential for full segmental aneuploid (Seg-A) embryos remains unclear. In this study, we investigated chromosomal concordance between clinically biopsied trophectoderm (TE) and inner cell mass (ICM) in 175 donated blastocysts, which comprised those clinically diagnosed as euploid (13), Seg-A (36), segmental mosaicism (Seg-M) (60), whole-chromosome aneuploid (Who-A) (52), and whole-chromosome mosaicism (14). Using next-generation sequencing (NGS), we found that TE–ICM concordance rates were higher for euploid (85%) and Who-A (94%) embryos but significantly lower for Seg-A (25%) and Seg-M embryos (33%). For Seg-A, the euploidy rate in the ICM was 19% and the euploidy rate in the ICM was 63% for Seg-M. These low concordance rates may be due to technical and biological artifacts of PGT-A for Seg-A. Despite the significant discordance between TE and ICM, a subset of Seg-A embryos demonstrated euploidy. While clinically diagnosed euploid embryos remain the preferred choice, Seg-A embryos should be considered as having implantation potential. In particular, Seg-A results should be clearly distinguished from Who-A results and not routinely categorically discarded. Further research is required to refine the selection criteria, aided by parental karyotyping or re-biopsy, and to develop more reliable embryo assessment methods to ensure the accurate evaluation of reproductive potential and support shared decision making between doctors and patients. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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18 pages, 4652 KiB

Open AccessArticle

The Temperature of the First Cleavage Impacts Preimplantation Development and Newborn Viability

by Aliya Stanova, Galina Kontsevaya, Alexander Romashchenko, Daniil Zuev, Elizaveta Silvanovich, Yuri Moshkin, Ludmila Gerlinskaya and Mikhail Moshkin

Int. J. Mol. Sci. 2025, 26(8), 3745; https://doi.org/10.3390/ijms26083745 - 16 Apr 2025

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Abstract

At the early developmental stage, embryos are susceptible to environmental factors, which modulate development trajectories. In our study, we examined how different incubation temperatures (35 °C, 37 °C, and 39 °C) in vitro during the first embryonic cleavage affect the morphology, cell division [...] Read more.

At the early developmental stage, embryos are susceptible to environmental factors, which modulate development trajectories. In our study, we examined how different incubation temperatures (35 °C, 37 °C, and 39 °C) in vitro during the first embryonic cleavage affect the morphology, cell division rate, and DNA methylation in two-, four-, and eight-cell embryos and the viability of these two-cell embryos transferred to recipient females. Embryos kept at 35 °C for the first 24 h after in vitro fertilization in two- and four-cell embryos at 37 °C showed enhanced variability in the size of blastomeres and DNA 5mC level among blastomeres, as compared to the groups kept at 37 °C and 39 °C. This was associated with the highest rate of embryo death in four- and eight-cell embryos and the highest viability of newborns. In contrast, incubation at 39 °C did not significantly impact developmental dynamics and viability in vitro but led to a notably higher rate of gestation failure compared to other groups. The indicators of the 37 °C group fell within an intermediate range. Therefore, we conclude that a decrease in temperature during zygotic genome activation (ZGA) highlights the adaptive potential of embryos during their initial cleavages, while an increase in temperature does not show clear effects on their fate. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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12 pages, 2184 KiB

Open AccessArticle

Microtubule Integrity Is Associated with Mitochondrial Function and Quality of Murine Preimplantation Embryos

by Yu-Ha Shim, Min-Jeong Cho, Min-Hee Kang, Yu-Jin Kim, Seung-A Oh, Ji-Soo Ryu, Byeong-Jun Mun, Jin-Young An and Jae-Ho Lee

Int. J. Mol. Sci. 2025, 26(7), 3268; https://doi.org/10.3390/ijms26073268 - 1 Apr 2025

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Abstract

Poor embryo quality is a major cause of poor clinical outcomes in assisted reproductive medicine, and there are no currently available interventions that can improve embryo quality. Mitochondria dysfunction is linked to low-quality female gametes and zygotes. Previously, microtubule integrity was also associated [...] Read more.

Poor embryo quality is a major cause of poor clinical outcomes in assisted reproductive medicine, and there are no currently available interventions that can improve embryo quality. Mitochondria dysfunction is linked to low-quality female gametes and zygotes. Previously, microtubule integrity was also associated with mitochondrial function in oocytes. In the present study, we investigated the effects of the microtubule stabilizers (MTS) Taxol and Epothilone D (EpD) and the microtubule disturber (MTD) vinorelbine on mouse preimplantation embryo quality and pregnancy outcome compared with non-treatment controls. We prepared young BDF1 mice (7~9 weeks old) and cultured preimplantation embryos with MTS or MTD. Mitochondrial functional activity and embryo development ratios including pregnancy ratios were then assessed. MTS-treated embryos showed significantly increased mitochondrial membrane potentials and motility. Blastocyst formation was significantly higher in MTS-treated embryos than in MTD-treated embryos. Especially, MTS-treated embryos exhibited higher hatched blastocyte formation than untreated embryos. The number of offspring was significantly higher in surrogate mice transplanted with MTS-treated embryos. These findings demonstrated that the treatment of mouse preimplantation embryos with Taxol or EpD increased embryo development competence, which was associated with increased mitochondrial functional activity. Consistently, delivery ratios were significantly higher after transplantation with MTS-treated embryos than after transplantation with untreated embryos. These findings suggest that MTS could be used to supplement in vitro culture media to promote the recovery of poor-quality embryos. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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17 pages, 5954 KiB

Open AccessArticle

Is There a Relationship Between Prenatal Dexamethasone and Postnatal Fructose Overexposure and Testicular Development, Function, and Oxidative Stress Parameters in Rats?

by Nataša Ristić, Slavica Borković-Mitić, Milica Manojlović-Stojanoski, Nataša Nestorović, Branko Filipović, Branka Šošić-Jurjević, Svetlana Trifunović, Bojan Mitić, Jovana Čukuranović-Kokoris and Slađan Pavlović

Int. J. Mol. Sci. 2024, 25(23), 13112; https://doi.org/10.3390/ijms252313112 - 6 Dec 2024

Cited by 1 | Viewed by 1049

Abstract

Prenatal glucocorticoid overexposure alters the developmental program of fetal reproductive organs and results in numerous changes that can lead to various disorders later in life. Moderate fructose consumption during childhood and adolescence may impair the development and function of reproductive organs. The aim [...] Read more.

Prenatal glucocorticoid overexposure alters the developmental program of fetal reproductive organs and results in numerous changes that can lead to various disorders later in life. Moderate fructose consumption during childhood and adolescence may impair the development and function of reproductive organs. The aim of this study was to investigate the effects of prenatal dexamethasone (Dx) exposure in combination with postnatal fructose overconsumption on testicular development and function in fetal and adult male rat offspring. Pregnant female rats were treated with a subcutaneous injection of Dx at a dose of 0.5 mg/kg/day on gestation days 16, 17, and 18, and the effects on fetal growth and testicular development were analyzed. Spontaneously born male offspring were fed 10% fructose in drinking water until the age of 3 months. Prenatal exposure to Dx led to a reduction in fetal weight and testicular volume. However, testicular development normalized by adulthood, with testosterone levels decreasing. After moderate fructose consumption, impaired redox homeostasis and structural changes in the testicles and decreased testosterone levels were observed, indicating reduced testicular function. The results suggest that the synergistic effect of prenatal Dx exposure and moderate postnatal fructose consumption leads to more deleterious changes in testicular tissue. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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12 pages, 1533 KiB

Open AccessArticle

Oocyte Competence, Embryological Outcomes and miRNA Signature of Different Sized Follicles from Poor Responder Patients

by Roberto Yagüe-Serrano, Andrea Palomar, Alicia Quiñonero, Víctor Hugo Gómez, Maria José de los Santos, Carmen Vidal and Francisco Dominguez

Int. J. Mol. Sci. 2024, 25(19), 10237; https://doi.org/10.3390/ijms251910237 - 24 Sep 2024

Cited by 1 | Viewed by 1519

Abstract

Poor ovarian response (POR) patients often face the risk of not having enough competent oocytes. Then, aspirating small follicles could serve as a strategy to increase their number. Many efforts have been addressed to associate follicular size with oocyte competence, but results are [...] Read more.

Poor ovarian response (POR) patients often face the risk of not having enough competent oocytes. Then, aspirating small follicles could serve as a strategy to increase their number. Many efforts have been addressed to associate follicular size with oocyte competence, but results are controversial. Therefore, our study aimed to evaluate oocyte maturation and developmental competence, along with a non-invasive oocyte-maturation-related miRNA signature in oocytes retrieved from both large and small follicles. A total of 178 follicles, from 31 POR patients, were aspirated and measured on the day of ovarian puncture. Follicular diameters, oocyte collection, oocyte maturation, fertilization, blastocysts, and good-quality blastocyst rates were recorded. Simultaneously, follicular fluids were collected to quantify their miRNA expression. The efficacy of oocyte retrieval along with oocyte maturation, fertilization, and blastulation rates tended to increase with follicular size, but few significant differences were found. Despite there being significantly more collected oocytes from follicles > 11.5 mm compared to follicles ≤ 11.5 mm (p < 0.05), oocytes from the latter were also mature, with no significant differences in the miRNA signature, but only those > 13.5 mm demonstrated developmental competence. In conclusion, 11.5 mm follicles can produce mature oocytes, but only those larger than 13.5 mm yielded transferable embryos. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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14 pages, 1953 KiB

Open AccessArticle

Navigating the Intersection of Glycemic Control and Fertility: A Network Perspective

by Carlo Di Carlo, Costanza Cimini, Ramses Belda-Perez, Luca Valbonetti, Nicola Bernabò and Barbara Barboni

Int. J. Mol. Sci. 2024, 25(18), 9967; https://doi.org/10.3390/ijms25189967 - 16 Sep 2024

Cited by 1 | Viewed by 1386

Abstract

The rising incidence of metabolic diseases is linked to elevated blood glucose levels, contributing to conditions such as diabetes and promoting the accumulation of advanced glycation end products (AGEs). AGEs, formed by non-enzymatic reactions between sugars and proteins, build up in tissues and [...] Read more.

The rising incidence of metabolic diseases is linked to elevated blood glucose levels, contributing to conditions such as diabetes and promoting the accumulation of advanced glycation end products (AGEs). AGEs, formed by non-enzymatic reactions between sugars and proteins, build up in tissues and are implicated in various diseases. This article explores the relationship between glycemic control and AGE accumulation, focusing on fertility implications. A computational model using network theory was developed, featuring a molecular database and a network with 145 nodes and 262 links, categorized as a Barabasi–Albert scale-free network. Three main subsets of nodes emerged, centered on glycemic control, fertility, and immunity, with AGEs playing a critical role. The transient receptor potential vanilloid 1 (TRPV1), a receptor expressed in several tissues including sperm, was identified as a key hub, suggesting that the modulation of TRPV1 in sperm by AGEs may influence fertility. Additionally, a novel link between glycemic control and immunity was found, indicating that immune cells may play a role in endocytosing specific AGEs. This discovery underscores the complex interplay between glycemic control and immune function, with significant implications for metabolic, immune health, and fertility. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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8 pages, 1570 KiB

Open AccessBrief Report

Association Between Activated Loci of HML-2 Primate-Specific Endogenous Retrovirus and Newly Formed Chromatin Contacts in Human Primordial Germ Cell-like Cells

by Bianca Cordazzo Vargas and Toshihiro Shioda

Int. J. Mol. Sci. 2024, 25(24), 13639; https://doi.org/10.3390/ijms252413639 - 20 Dec 2024

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Abstract

The pluripotent stem cell (PSC)-derived human primordial germ cell-like cells (PGCLCs) are a cell culture-derived surrogate model of embryonic primordial germ cells. Upon differentiation of PSCs to PGCLCs, multiple loci of HML-2, the hominoid-specific human endogenous retrovirus (HERV), are strongly activated, which is [...] Read more.

The pluripotent stem cell (PSC)-derived human primordial germ cell-like cells (PGCLCs) are a cell culture-derived surrogate model of embryonic primordial germ cells. Upon differentiation of PSCs to PGCLCs, multiple loci of HML-2, the hominoid-specific human endogenous retrovirus (HERV), are strongly activated, which is necessary for PSC differentiation to PGCLCs. In PSCs, strongly activated loci of HERV-H family HERVs create chromatin contacts, which are required for the pluripotency. Chromatin contacts in the genome of human PSCs and PGCLCs were determined by Hi-C sequencing, and their locations were compared with those of HML-2 loci strongly activated in PGCLCs but silenced in the precursor naïve iPSCs. In both iPSCs and PGCLCs, the size of chromatin contacts were found to be around one megabase, which corresponds to the Topologically Associated Domains in the human genome but is slightly larger in PGCLCs than iPSCs. The number of small-sized chromatin contacts diminished while numbers of larger-sized contacts increased. The distances between chromatin contacts newly formed in PGCLCs and the degrees of activation of the closest HML-2 loci showed significant inverse correlation. Our study provides evidence that strong activation of HML-2 provirus loci may be associated with newly formed chromatin contacts in their vicinity, potentially contributing to PSC differentiation to the germ cell lineage. Full article

(This article belongs to the Special Issue Latest Advances in Reproduction Biology)

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