Reproduction最新文献

Endometrial stromal cell decidualization is required for pregnancy success. Although this process is integral to fertility, many of the intricate molecular mechanisms contributing to decidualization remain undefined. One pathway that has been implicated in endometrial stromal cell decidualization in humans in vitro, is the Hippo signaling pathway. Two previously conducted studies showed that the effectors of the Hippo signaling pathway, YAP1 and WWTR1, are required for decidualization of primary endometrial stromal cells in vitro. To investigate the in vivo role of YAP1 and WWTR1 in decidualization and pregnancy initiation, we generated Progesterone receptor Cre mediated mutation of a combination of Yap1 and Wwtr1 alleles. Female Yap1 and Wwtr1 triple allele mutants exhibited subfertility, a compromised decidualization response, decreased endometrial receptivity, delayed embryonic development, and a unique transcriptional profile at 7.5 days post coitus. Bulk mRNA sequencing revealed aberrant maternal remodeling evidenced by significant alterations in extracellular matrix encoding genes at 7.5 days post-coitus in mutant dams and enrichment for terms associated with fertility-compromising diseases like pre-eclampsia and endometriosis. In addition, differentially expressed genes overlapped directionally with Estrogen receptor and Epidermal growth factor receptor regulated genes as identified by microarray. Our results indicate that Yap1 and Wwtr1 are necessary for successful mammalian pregnancy initiation.

Spatial genome organization refers to the conformation of the chromosomes and their relative positioning within the nucleus. In mammals, fertilization entails intense chromatin remodeling of parental genomes, as well as large-scale structural changes in nuclear organization of the newly formed zygote over the first two cell cleavages. The molecular characteristics, mechanisms and functionality of spatial genome organization during the early steps of development in mouse have been extensively studied and will be presented in this review, with a specific focus on heterochromatin. Concomitantly to maturation of genomic architecture, the embryonic genome activation occurs in transient waves of transcription. Here, we will also discuss the putative link between heterochromatin organization and the regulation of genome expression.

Granulosa cells in the ovaries of livestock are crucial for secreting steroid hormones that regulate follicular development, with lipid synthesis and metabolism playing key roles in this process. The molecular mechanisms behind steroid hormone secretion regulated by fatty acid metabolism in goat granulosa cells have been unclear. Our previous transcriptome analysis of Yunshang black goat ovaries revealed that miR-novel-216, which had lower expression in high-fertility goats, might regulate granulosa cell function. We further investigated the role of miR-novel-216 by isolating and culturing goat granulosa cells in vitro, and found that it inhibits cell proliferation, lipid accumulation, and progesterone synthesis in goat granulosa cells. The qTar and miRanda analyses predicted TPD52 as a target of miR-novel-216, confirmed by dual luciferase and transfection assays. Previous studies have shown that progesterone synthesis in granulosa cells is closely related to free fatty acid composition. We investigated the effect of in vitro construction of TPD52 overexpression and interference plasmids on the free fatty acid content of goat granulosa cells using mass spectrometry sequencing. The results showed that overexpression of TPD52 in goat granulosa cells significantly increased free fatty acid content and promoted granulosa cell proliferation, lipid accumulation, and progesterone synthesis, whereas the opposite was true for inhibition of TPD52. It was shown that miR-novel-216 affects granulosa cell proliferation and free fatty acid levels by regulating the expression of TPD52, which increases reproductive hormone secretion and promotes polytocous trait in goats. This provides a foundation for developing breeding strategies to improve goat fertility.

Metabolic syndrome (MS) is increasingly associated with impaired reproductive health. This study aimed to assess the endometrial characteristics and reproductive outcomes of a female MS mouse model and evaluate metformin's therapeutic effects. Twenty-one-day-old female C57BL/6 mice were randomly divided into a high-fat diet group (N = 50) and a control group (N = 30) that received standard chow. After 11 weeks, a subset of HF mice (N = 25) was given oral metformin at 300 mg/kg/day, while the other ones continued on HF diet. After 15 weeks, mice were either sacrificed during estrus or mated and euthanized on day 7.5 of pregnancy (N = 15 per group). The estrous cycle, progesterone and estradiol levels, uterine morphology, endometrial cell proliferation, reproductive performance, and metformin's treatment effects were assessed. Mice on a high-fat diet developed MS, which was characterized by moderate glycemic dysregulation, increased cholesterol, insulin resistance, and central obesity. Experimental MS caused estrous cycle disruptions and increased serum progesterone levels, which were normalized by metformin. MS also affected endometrial histology, producing hyperplasia and altering cell proliferation, while metformin restored normal endometrial architecture by inhibiting cell proliferation. Additionally, MS impaired reproductive success by delaying coitus and reducing the ratio of implantation sites to corpora lutea, both of which were rectified by metformin. In conclusion, MS adversely affects reproductive function, but metformin offers improvement. Our findings highlight the need for further research on the impact of MS on reproduction and the exploration of treatments to enhance reproductive health in women with MS.

Bisphenol-A (BPA), an environmental endocrine disruptor (EED), is used widely in the manufacturing of various plastics. While BPA can have detrimental effects on fertility and reproductive health, the effects of BPA on early ovarian differentiation in mammals remains unclear. Marsupials have undifferentiated gonads at birth, so this study investigated the gross morphology, protein localisation of FOXL2 and FST and the expression profile of key ovarian differentiating genes FOXL2, WNT4,FST, ESR1 and ESR2 every 2 days from the day of birth to day 10 post partum (pp) in the marsupial tammar wallaby. A second group of newborn female pouch young were treated with 50 µg/kg of BPA daily from day 0-10 pp and the morphology and gene expression were examined at day 10 pp. Ovigerous cords in tammar ovaries were first formed between days 2 to 4 pp. FOXL2 localisation became nuclear by day 4 in pre-granulosa cells. FST was initially in the cytoplasm of pre-granulosa cells at day 2 pp, but was then secreted into the extracellular matrix in ovaries by day 10 pp. FOXL2, FST, ESR1 and ESR2 mRNA were upregulated in ovaries around day 2-4 pp, indicating that ovarian differentiation in the tammar begins from day 2-4 pp. Interestingly, BPA treatment from day 0-10 pp blocked the morphological differentiation of the cortex and medulla as well as ovigerous cord formation and downregulated the expression of FST and FOXL2 at day 10 pp.

The morphological diversity and functional role of the organs of the female reproductive system across tetrapods (limbed vertebrates) are relatively poorly understood. Though some features are morphologically similar, species-specific modification makes comparisons between species and inference about evolutionary origins challenging. In combination with the study of morphological changes, studying differences in gene expression in the adult reproductive system in diverse species can clarify the function of each organ. Here, we use the brown anole, Anolis sagrei, to study gene expression differences within the reproductive tract of the adult female. We generated gene expression profiles of four biological replicates of the three regions of the female reproductive tract, the infundibulum, glandular uterus, and nonglandular uterus by RNA-sequencing. We aligned read to the recently published Anolis sagrei genome and identified significantly differentially expressed genes between the regions using DEseq2. Each organ expressed approximately 14600 genes and comparison of gene expression profiles between organs revealed between 367-883 differentially expressed genes. We identify shared and region-specific transcriptional signatures for the three regions and compare gene expression in the brown anole reproductive tract to known gene expression patterns in other tetrapods. We find that genes in the Hox cluster have an anterior-posterior, colinear expression pattern as has been described in mammals. We also define a secretome for the glandular uterus. These data provide fundamental information for functional studies of the reproductive tract organs in the brown anole as well as an important phylogenetic anchor for comparative study of the evolution of the female reproductive tract.

Extensive research indicates that fertilization outcomes are shaped by individual female and male traits that reflect their intrinsic quality. Yet, surprisingly little is known about the influence of interactions between the sexes and their adaptive significance in either externally or internally fertilizing species. Here, we review empirical evidence on how female-male interactions influence each stage of the fertilization process, including sperm transfer, transport, storage, chemoattraction and fertilization. We also address the challenges of examining female-male interaction effects within a realistic biological context and why research in this area lags behind understanding the role of individual sex-specific traits. While relatively little data are currently available to address interactive effects between the sexes and their impact on the fertilization process, what is presently known suggests these effects are likely to be more common across the animal tree of life than appreciated. Future research will help to not only identify these interactions, but their understanding can also help to explain the maintenance of genetic variation and inform applied studies of fertility.

This review article summarizes the experimental findings in rodents published between 2014 and 2024 concerning phthalates exposure and reproductive outcomes. Rodents were chosen for this review since most studies that have developmental aspects in different phases of exposure and that address more in-depth reproductive mechanisms have been carried out in mice and rats. The evidence of adverse effects of phthalates on fetal development and human and animal reproduction is extensive, with impacts ranging from gene expression to physiological alterations. Despite the large volume of scientific papers pointing out the harmful effects of exposure to phthalates, isolated or in mixtures, at different developmental periods, most of them are associated with the maternal exposure and long-term effects in the offspring. Regular vegetables, fruits, fish, dairy products, and whole grains intake rich in bioactive compounds can mitigate the adverse effects of EDCs in humans and animals at different developmental periods. Various food bioactive compounds (FBCs) such as genistein, resveratrol, lycopene, vitamin E, curcumin, selenium, and plant secondary metabolites (PSMs) present antioxidant, anti-inflammatory, anti-tumor, and other biological properties with the potential to reduce of deleterious effects of phthalates on the reproductive tract. In this review, we aimed to summarize the main studies produced in the last decade about phthalate exposure and reproductive disorders in males and females (at different developmental critical windows). Additionally, we proposed some FBCs and PSMs that could attenuate the main adverse effects caused by phthalate exposure on male reproduction since there is a lack of studies with females.

Daily exposure to a mixture of phthalates is unavoidable in humans and poses a risk to reproductive health because they are known endocrine-disrupting chemicals. Specific to female reproductive health, the literature has linked phthalate exposure to impairments in ovarian function, uterine function, pregnancy outcomes, and endocrine signaling in the hypothalamus-pituitary-ovarian axis. However, limitations to these studies are that they primarily focus on single phthalate exposures in animal models. Thus, the effects of real life exposures to mixtures of phthalates and the clinical and translational impacts on reproductive function in women are largely unknown. This review summarizes recent literature specifically investigating associations between phthalate mixture exposures and clinical reproductive outcomes and reproductive disease states in women. Because these studies are scarce, they are supplemented with literature utilizing single phthalate analyses in women and mechanistic basic science studies using phthalate mixture exposures. Main findings from the literature suggest that elevated phthalate exposure is associated with altered menstrual cyclicity, altered pubertal timing, disrupted ovarian folliculogenesis and steroidogenesis, ovarian disorders including primary ovarian insufficiency and polycystic ovary syndrome, uterine disorders including endometriosis and leiomyomas, poor in vitro fertilization outcomes, and poor pregnancy outcomes. There is an urgent need to better incorporate phthalate mixtures in epidemiology (mixture analyses) and basic science (direct exposures) study designs. Further, as exposure to multiple phthalates is ubiquitous, elucidating the mechanism of phthalate mixture toxicities is paramount for improving women's reproductive health.

In brief: Alpha-ketoglutarate is a common metabolite in the tricarboxylic acid cycle and is central in modulating the reproductive potential in animal models. The present scoping review systematically covers the spectrum of a wide range of evidence from different viewpoints, focusing on the underlying processes and mechanisms of the developmental framework, aiming to fill the gaps within the existing literature.

Abstract: Alpha-ketoglutarate is an important intermediate molecule in the tricarboxylic acid cycle with a prominent role in distinct biological processes such as cellular energy metabolism, epigenetic regulation, and signaling pathways. We conducted a registered scoping review (OSF: osf.io/b8nyt) to explore the impact of exogenous supplementation on reproductive capabilities. Our strategy included evaluating the main research literature from different databases like PubMed-MEDLINE, Web of ScienceTM, Scopus, and Excerpta Medica dataBASE using a specific systematic layout to encompass all investigations based on experimental models and critically compare the results. Twenty-one studies were included in the main body of this manuscript, which revealed that exogenous supplementation induced dose- and sex-dependent modifications. This metabolite modulates the expression of pluripotency genes, thus controlling stem cells' self-renewal, differentiation, and reprogramming dynamics, while also alleviating structural transformations induced by exposure to heavy metals and other inhibitors. This significantly demonstrated a direct influence of alpha-ketoglutarate in mitigating oxidative stress and prolonging the lifespan, consequently supporting metabolic and endocrine adjustments. It influences oocyte quality and quantity, delays reproductive aging, and establishes an optimal competence framework for development with minimal risk of failure. Therefore, alpha-ketoglutarate is linked to improving reproductive performance, but further studies are needed due to a lack of studies on humans.