Molecular Reproduction and Development最新文献

Recurrent spontaneous abortions (RSA) are defined as a loss of two or more consecutive clinically recognized pregnancies before the 20th week of gestation. In RSA, several causative factors are known, but still, 50% of the cases remain unexplained. Two large clusters of microRNAs (miRNAs), namely C14MC (Chromosome 14 microRNA cluster) and C19MC (Chromosome 19 microRNA cluster), are imprinted and expressed in the placenta. Hence, we studied the expression of miRNAs coded by these clusters and their mRNA targets in RSA cases in order to elucidate the involvement of these two clusters in the pathogenesis of RSA. Upon miRNA sequencing, we found a total of seven miRNAs to be differentially expressed in RSA group. Further, using bioinformatics tools such as TargetScan and DAVID pathway analysis, we found that the mRNA targets were involved in the functionally relevant processes of the placenta such as cell migration, cell–cell adhesion, and angiogenesis. Upon validation of sequencing data, we found differential expression of five miRNAs from C14MC and C19MC clusters and differential expression of genes regulating processes such as cell migration, cell adhesion, and angiogenesis in RSA cases which are targeted by these miRNAs.

The synthesis and degradation of Cyclins are critical for cell cycle progression. Cyclin K (CCNK), a member of the Cyclin family, is known to regulate transcriptional elongation and the MAPK signaling pathway by binding to CDK12/13. While CCNK has been extensively studied in cancers, its roles in oocyte maturation remains unclear. In this study, we found that overexpression of CCNK accelerates the resumption of meiosis in oocytes. This effect is primarily attributed to the early nuclear entry of Cyclin B1 (CCNB1) and the premature activation of maturation promoting factor. These findings suggest that CCNK plays a vital role in the process of oocyte maturation, and its dysregulation could disrupt the normal progression of meiosis.

Diabetes-associated spermatogenic dysfunction remains mechanistically unclear despite its clinical significance. We aimed to elucidate the effect and molecular mechanism of sperm damage induced by type 2 diabetes mellitus (T2DM). In a mouse model of T2DM, transcriptome sequencing identified Art1 as a differentially expressed gene. T2DM induced structural damage to the seminiferous tubules, deregulated sperm parameters, and suppressed Art1 expression in mice and caused reproductive damage in their offspring. Danshensu administration rescued these pathologies. In vitro, high-glucose/high-lipid exposure induced GC-2 cell damage, while Art1 overexpression reduced oxidative stress and apoptosis. Art1-knockout mice exhibited impaired sperm motility and tubule structural defects, confirming Art1's critical role in spermatogenesis maintenance. This study demonstrated that T2DM triggers testicular oxidative stress, apoptosis, and Art1 suppression, leading to transgenerational reproductive dysfunction. Experiments have shown that the overexpression of Danshensu or Art1 can rescue these pathological damages. The results from the Art1-knockout mice confirm the indispensable regulatory role of Art1 in spermatogenesis maintenance. We speculate that T2DM may impair male reproductive ability by inhibiting the expression of Art1, which will provide a new molecular target and theoretical basis for further investigation into the interaction mechanism between T2DM and the reproductive system.

The search for male-biased genes that may drive sexual differentiation in sturgeon gonadal tissue has remained largely fruitless until now. This study explored the presence, expression, and sexual steroid regulation of gonadal soma-derived factor (Gsdf) in Siberian sturgeon (Acipenser baerii). Three sequences compatible with the protein-coding gene gsdf were identified in a Siberian sturgeon gonadal transcriptome database. The phylogenetic analysis shows the presence of two paralogues gsdfa and gsdfb, and two clearly identifiable gsdfa isoforms (gsdfa1 and gsdfa2). gsdfa was expressed in sex-undifferentiated gonads, brain, hypophysis, heart, interrenal, intestine, liver, stomach, embryos and larvae, while gsdfb was specific to the gonads. gsdfb showed significantly higher expression in genetically sexed males during late stage of sex differentiation. In contrast, gsdfa1 and gsdfa2 showed similar gonadal expression levels in both sexes. In terms of sensitivity to sexual steroids, only gsdfb was repressed significantly and in a dose-dependent manner by estrogens. Taken together, these results indicate both that gsdfb is part of the male gonadal differentiation pathway in sturgeon and that its repression by estrogens is fundamental for female development.

Yellowish myotis presented four reproductive stages and long-term sperm storage in cauda epididymis. Aiming to investigate the morphofunctional aspects of the epididymis and spermatozoa of yellowish myotis, 48 adult male bats were captured in Santuário do Caraça, Minas Gerais, Brazil, for histomorphometric evaluations of the epididymis and sperm analysis. Yellowish myotis spermatozoa were observed in the caput and corpus epididymis only during the Mature and Regressed stages, coinciding with increased epithelial height in these stages, indicating their possible role in sperm maturation. In contrast, spermatozoa were found in the cauda epididymis during all reproductive stages, with the epithelium maintaining a consistent height, which suggests that this region is adapted for long-term sperm storage. The spermatozoa remained alive and motile for up to 25 days during the Regressed and Early Rest stages. Mating period in yellowish myotis occurs during the Rest stage, when spermatozoa in the cauda epididymis exhibit reduced DNA fragmentation and minimal chromatin abnormalities. During this period, sperm with wider heads and longer midpieces dominate, reflecting selection for traits that would enhance fertilization success. These results reinforced the importance of cauda epididymis physiology for sperm survival and future events of capacitation and fertilization.

FOXR1 belongs to the large conserved F-box family of DNA binding transcription factors that are involved in various developmental processes and diseases. The gene is important for embryogenesis in a fish model, brain development in mammals, and human FOXR1 was shown to possess oncogenic properties when it is abnormally expressed as a fusion gene. Earlier work on Foxr1 expression in mouse and human suggested roles for the protein in embryogenesis and sexual reproduction. We generated a mouse gene deletion model that revealed an embryonic lethal phenotype with partial penetrance and normal fertility in persistent homozygous male mutants. The results suggest that Foxr1 is functionally redundant in adult male gonads but needed for normal early embryo development and post-natal viability. We discuss our results in the context of publicly available human and rodent genomic and genetic data.

This study aimed to assess differences in the immunostaining intensity of follicle-stimulating hormone receptor (FSHr) and leutenizing hormone receptor (LHr) receptors in the ovarian follicles of Bos indicus cows with high or low antral follicle counts (AFCs). Ovaries from cyclic Nelore cows (N = 20) were obtained from a local slaughterhouse and classified based on AFC (≥ 3 mm) into high- (≥ 30 follicles, N = 10) and low- (≤ 15 follicles, N = 10) AFC groups. Immunohistochemical studies were performed for FSHr and LHr. Immunostaining intensity was measured using ImageJ software with the IHC Profiler plugin, and pixel intensity was measured on a scale of 0 (darkest) to 255 (lightest). An interaction was observed between the AFC group and follicular developmental stage for FSHr immunostaining intensity, with preantral follicles from the low-AFC group showing highest immunostaining intensity (p < 0.0001). The FSHr immunostaining intensity of antral follicles from the low-AFC group was higher than that of the high-AFC group (p = 0.03). LHr immunostaining intensity also was higher in the low-AFC group than in the high-AFC group (p = 0.002). These findings suggest that ovarian follicle characteristics of low-AFC cows have distinct characteristics that could affect their response to reproductive treatments.