Fertilization induces reproductive changes in male mouse offspring and has multigenerational effects.

fertilization (IVF) is a non-coital method of conception used to treat human infertility. Although IVF is viewed as largely safe, it is associated with adverse outcomes in the fetus, placenta, and adult offspring life. Because studies focusing on the effect of IVF on the male reproductive system are limited, we used a mouse model to assess the morphological and molecular effects of IVF on male offspring.

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival.

The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGO) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the ovarian reserve.

Kick-starting the zygotic genome: licensors, specifiers, and beyond.

Zygotic genome activation (ZGA), the first transcription event following fertilization, kickstarts the embryonic program that takes over the control of early development from the maternal products. How ZGA occurs, especially in mammals, is poorly understood due to the limited amount of research materials. With the rapid development of single-cell and low-input technologies, remarkable progress made in the past decade has unveiled dramatic transitions of the epigenomes, transcriptomes, proteomes, and metabolomes associated with ZGA.

Trophectoderm biopsy of blastocysts following IVF and embryo culture increases epigenetic dysregulation in a mouse model.

Study Question: Does trophectoderm biopsy (TEBx) of blastocysts for preimplantation genetic testing in the clinic affect normal placental and embryo development and offspring metabolic outcomes in a mouse model?

Summary Answer: TEBx impacts placental and embryonic health during early development, with some alterations resolving and others worsening later in development and triggering metabolic changes in adult offspring.

What Is Known Already: Previous studies have not assessed the epigenetic and morphological impacts of TEBx either in human populations or in animal models.

Study Design, Size, Duration: We employed a mouse model to identify the effects of TEBx during IVF.

KRAB-zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution.

As transposable elements (TEs) coevolved with the host genome, the host genome exploited TEs as functional regulatory elements. What remains largely unknown are how the activity of TEs, namely, endogenous retroviruses (ERVs), are regulated and how TEs evolved in the germline. Here we show that KRAB domain-containing zinc-finger proteins (KZFPs), which are highly expressed in mitotically dividing spermatogonia, bind to suppressed ERVs that function following entry into meiosis as active enhancers.

CHK1-CDC25A-CDK1 regulate cell cycle progression and protect genome integrity in early mouse embryos.

After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated and transcriptionally quiescent cells into early cleavage-stage blastomeres that are transcriptionally active and totipotent. This developmental transition is accompanied by cell cycle adaptation, such as lengthening or shortening of the gap phases G1 and G2. However, regulation of these cell cycle changes is poorly understood, especially in mammals.

New twists of a TAIL: novel insights into the histone binding properties of a highly conserved PHD finger cluster within the MLR family of H3K4 mono-methyltransferases.

Enhancer activation by the MLR family of H3K4 mono-methyltransferases requires proper recognition of histones for the deposition of the mono-methyl mark. MLR proteins contain two clusters of PHD zinc finger domains implicated in chromatin regulation. The second cluster is the most highly conserved, preserved as an ancient three finger functional unit throughout evolution.

OBOX regulates mouse zygotic genome activation and early development.

Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition. However, the identity of transcription factors that underlie mammalian ZGA in vivo remains elusive. Here we show that OBOX, a PRD-like homeobox domain transcription factor family (OBOX1-OBOX8), are key regulators of mouse ZGA.

Epigenetic programming in the ovarian reserve.

The ovarian reserve defines female reproductive lifespan, which in humans spans decades. The ovarian reserve consists of oocytes residing in primordial follicles arrested in meiotic prophase I and is maintained independent of DNA replication and cell proliferation, thereby lacking stem cell-based maintenance. Largely unknown is how cellular states of the ovarian reserve are established and maintained for decades.

Histone remodeling reflects conserved mechanisms of bovine and human preimplantation development.

How histone modifications regulate changes in gene expression during preimplantation development in any species remains poorly understood. Using CUT&Tag to overcome limiting amounts of biological material, we profiled two activating (H3K4me3 and H3K27ac) and two repressive (H3K9me3 and H3K27me3) marks in bovine oocytes, 2-, 4-, and 8-cell embryos, morula, blastocysts, inner cell mass, and trophectoderm. In oocytes, broad bivalent domains mark developmental genes, and prior to embryonic genome activation (EGA), H3K9me3 and H3K27me3 co-occupy gene bodies, suggesting a global mechanism for transcription repression.

Embryonic microRNAs are essential for bovine preimplantation embryo development.

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression after transcription. miRNAs are present in transcriptionally quiescent full-grown oocytes and preimplantation embryos that display a low level of transcription prior to embryonic genome activation. The role of miRNAs, if any, in preimplantation development is not known.

PRC1-mediated epigenetic programming is required to generate the ovarian reserve.

The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest.

Placental Abnormalities are Associated With Specific Windows of Embryo Culture in a Mouse Model.

Assisted Reproductive Technologies (ART) employ gamete/embryo handling and culture to produce offspring. ART pregnancies have an increased risk of low birth weight, abnormal placentation, pregnancy complications, and imprinting disorders. Embryo culture induces low birth weight, abnormal placental morphology, and lower levels of DNA methylation in placentas in a mouse model of ART.

CDC25B is required for the metaphase I-metaphase II transition in mouse oocytes.

Mammalian oocytes are arrested at meiotic prophase I. The dual-specificity phosphatase CDC25B is essential for cyclin-dependent kinase 1 (CDK1) activation that drives resumption of meiosis. CDC25B reverses the inhibitory effect of the protein kinases WEE1 and MYT1 on CDK1 activation.

Understanding stream bank erosion and deposition in Iowa, USA: A seven year study along streams in different regions with different riparian land-uses.

Agricultural activities such as row-cropping and grazing, have accelerated stream bank erosion. Accelerated stream bank erosion increases nonpoint source pollutants in aquatic ecosystems, significantly degrading them. Mitigating stream bank erosion is a priority worldwide, especially in agricultural watersheds.

Sex-specific effects of in vitro fertilization on adult metabolic outcomes and hepatic transcriptome and proteome in mouse.

Although in vitro fertilization (IVF) is associated with adverse perinatal outcomes, there is increasing concern about the long-term and sex-specific health implications. Augmenting our IVF mouse model to longitudinally investigate metabolic outcomes in offspring from optimal neonatal litter sizes, we found sex-specific metabolic outcomes in IVF offspring. IVF-conceived females had higher body weight and cholesterol levels compared to naturally conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition.

Unscrambling the oocyte and the egg: clarifying terminology of the female gamete in mammals.

Most reproductive biologists who study female gametes will agree with the 16th century anatomist William Harvey's doctrine: 'Ex Ovo Omnia'. This phrase, which literally translates to 'everything from the egg', recognizes the centrality of the egg in animal development. Eggs are most impressive cells, capable of supporting development of an entirely new organism following fertilization or parthenogenetic activation.

Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation.

The shift from maternal to embryonic control is a critical developmental milestone in preimplantation development. Widespread transcriptomic and epigenetic remodeling facilitate this transition from terminally differentiated gametes to totipotent blastomeres, but the identity of transcription factors (TF) and genomic elements regulating embryonic genome activation (EGA) are poorly defined. The timing of EGA is species-specific, e.

Long-term nitrate removal in three riparian buffers: 21 years of data from the Bear Creek watershed in central Iowa, USA.

Riparian buffers are a conservation practice that increases vegetation diversity on the agricultural landscape while providing environmental benefits. This study specifically focused on the ability of riparian buffers to remove nitrate from shallow groundwater. There are many studies that assessed nitrate removal within buffers, but not many have a long-term, continuous data set that can analyze for variation in nitrate removal rates over time.

Assisted reproductive technologies induce temporally specific placental defects and the preeclampsia risk marker sFLT1 in mouse.

Although widely used, assisted reproductive technologies (ARTs) are associated with adverse perinatal outcomes. To elucidate their underlying causes, we have conducted a longitudinal analysis of placental development and fetal growth using a mouse model to investigate the effects of individual ART procedures: hormone stimulation, fertilization (IVF), embryo culture and embryo transfer. We demonstrate that transfer of blastocysts naturally conceived without hormone stimulation and developed prior to transfer can impair early placentation and fetal growth, but this effect normalizes by term.

Transcript profiling of bovine embryos implicates specific transcription factors in the maternal-to-embryo transition.

Full-grown oocytes are transcriptionally quiescent. Following maturation and fertilization, the early stages of embryonic development occur in the absence (or low levels) of transcription that results in a period of development relying on maternally derived products (e.g.

Characterization of Historical Methane Occurrence Frequencies from U.S. Underground Natural Gas Storage Facilities with Implications for Risk Management, Operations, and Regulatory Policy.

Defining a baseline for the frequency of occurrences at underground natural gas storage facilities is critical to maintaining safe operation and to the development of appropriate risk management plans and regulatory approaches. Currently used frequency-estimation methods are reviewed and broadened in this article to include critical factors of cause, severity, and uncertainty that contribute to risk. A Bayesian probabilistic analysis characterizes the aleatoric historical occurrence frequencies given imperfect sampling.

Anthropogenic litter cleanups in Iowa riparian areas reveal the importance of near-stream and watershed scale land use.

Volunteer cleanup operations collect large datasets on anthropogenic litter that are seldom analyzed. Here we assess the influence of land use in both near-stream and watershed scale source domains on anthropogenic litter concentration (standing stock, kg km) in riparian zones of Iowa, USA. We utilized riparian litter concentration data on four classes of anthropogenic litter (metal, recyclable, garbage, and tires) from volunteer cleanup operations.