The severity of meiotic aneuploidy is associated with altered morphokinetic variables of mouse oocyte maturation.

Study Question: Is there an association between morphokinetic variables of meiotic maturation and the severity of aneuploidy following maturation (IVM) in the mouse?

Summary Answer: The severity of meiotic aneuploidy correlates with an extended time to first polar body extrusion (tPB1) and duration of meiosis I (dMI).

What Is Known Already: Morphokinetic variables measured using time-lapse technology allow for the non-invasive evaluation of preimplantation embryo development within clinical assisted reproductive technology (ART). We recently applied this technology to monitor meiotic progression during IVM of mouse gametes.

A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.

To accurately phenocopy human biology , researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur . However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows.

Morphokinetic parameters of mouse oocyte meiotic maturation and cumulus expansion are not affected by reproductive age or ploidy status.

Introduction: Morphokinetic analysis using a closed time-lapse monitoring system (EmbryoScope + ™) provides quantitative metrics of meiotic progression and cumulus expansion. The goal of this study was to use a physiologic aging mouse model, in which egg aneuploidy levels increase, to determine whether there are age-dependent differences in morphokinetic parameters of oocyte maturation.

Methods: Denuded oocytes and intact cumulus-oocyte complexes (COCs) were isolated from reproductively young and old mice and in vitro matured in the EmbryoScope + ™.

Quantitative morphokinetic parameters identify novel dynamics of oocyte meiotic maturation and cumulus expansion†.

Meiotic maturation and cumulus expansion are essential for the generation of a developmentally competent gamete, and both processes can be recapitulated in vitro. We used a closed time-lapse incubator (EmbryoScope+™) to establish morphokinetic parameters of meiotic progression and cumulus expansion in mice and correlated these outcomes with egg ploidy. The average time to germinal vesicle breakdown (GVBD), time to first polar body extrusion (PBE), and duration of meiosis I were 0.

SPERM FACTORS AND EGG ACTIVATION: ICSI and the discovery of the sperm factor and PLCZ1.

The discovery of PLCZ1 nearly 20 years ago as the primary Ca2+ oscillation-inducing factor in the sperm of mammals represented a significant breakthrough in our quest to elucidate the molecules and pathways that promote egg activation during fertilization. The advent of the intracytoplasmic sperm injection (ICSI) technique, which made fertilization possible without sperm capacitation, acrosome reaction, and gamete fusion, strengthened the research that led to the discovery of PLCZ1 and became an essential clinical tool for humans. The use of ICSI combined with the detection of PLCZ1 expression and mutations in infertile patients established the fundamental role of PLCZ1 in human fertility while leading to the discovery of novel components of the perinuclear theca, the site of the residence of PLCZ1 in sperm before fertilization.

A decellularized oocyte-derived scaffold provides a "sperm safe" to preserve mammalian spermatozoa.

Background: Although only one spermatozoon is needed to create a zygote, a significant challenge is the storage and recovery of germ cells when sperm counts are extremely low.

Objectives: We engineered an oocyte-derived biomaterial-the zona pellucida (ZP)-as a "sperm safe" for storing spermatozoon. The ZP is a glycoprotein matrix that surrounds the mammalian oocyte.

Prospects of Rescuing Young Eggs for Oncofertility.

Childhood cancer patients undergoing cancer therapy can be rendered infertile during adulthood. With more girls surviving cancer, fertility preservation in young cancer patients is a major clinical challenge. Advances in egg culture may offer benefits for the fertility of these patients in the future.

Association between dental caries and adverse pregnancy outcomes.

Poor oral health is not only associated with diabetes and cardiovascular disease but adverse pregnancy outcomes. However the influence of dental caries on pregnancy is unknown. The aim of this study was to evaluate the association between dental caries and adverse pregnancy outcomes and the effect of treatment for dental caries on adverse pregnancy outcomes.

Zinc exocytosis is sensitive to myosin light chain kinase inhibition in mouse and human eggs.

Zinc dynamics are essential for oocyte meiotic maturation, egg activation, and preimplantation embryo development. During fertilisation and egg activation, the egg releases billions of zinc atoms (Zn2+) in an exocytotic event termed the 'zinc spark'. We hypothesised that this zinc transport and exocytosis is dependent upon the intracellular trafficking of cortical granules (CG) which requires myosin-actin-dependent motors.

Poorly-Controlled Type 1 Diabetes Mellitus Impairs LH-LHCGR Signaling in the Ovaries and Decreases Female Fertility in Mice.

Purpose: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development.

Materials And Methods: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone).

Risk of Adverse Obstetric Outcomes and the Abnormal Growth of Offspring in Women with a History of Thyroid Cancer.

It is unclear whether a history of thyroid cancer is associated with an increased risk of adverse pregnancy outcomes in subsequent pregnancies. This study aimed to evaluate the risk of adverse obstetric outcomes and the abnormal growth of offspring in women with a history of thyroid cancer. This retrospective observational study used nationwide data from between 2006 and 2014 to compare pregnancy outcomes of women with a history of thyroid cancer and those with no such history.

Retrievable hydrogels for ovarian follicle transplantation and oocyte collection.

Cancer survivorship rates have drastically increased due to improved efficacy of oncologic treatments. Consequently, clinical concerns have shifted from solely focusing on survival to quality of life, with fertility preservation as an important consideration. Among fertility preservation strategies for female patients, ovarian tissue cryopreservation and subsequent reimplantation has been the only clinical option available to cancer survivors with cryopreserved tissue.

Defective sperm head decondensation undermines the success of ICSI in the bovine.

The efficiency of intracytoplasmic sperm injection (ICSI) in the bovine is low compared to other species. It is unknown whether defective oocyte activation and/or sperm head decondensation limit the success of this technique in this species. To elucidate where the main obstacle lies, we used homologous and heterologous ICSI and parthenogenetic activation procedures.

PLCζ is the physiological trigger of the Ca oscillations that induce embryogenesis in mammals but conception can occur in its absence.

Activation of the egg by the sperm is the first, vital stage of embryogenesis. The sperm protein PLCζ has been proposed as the physiological agent that triggers the Ca oscillations that normally initiate embryogenesis. Consistent with this, recombinant PLCζ induces Ca oscillations in eggs and debilitating mutations in the gene are associated with infertility in men.

TRPM7-like channels are functionally expressed in oocytes and modulate post-fertilization embryo development in mouse.

The Transient Receptor Potential (TRP) channels are a family of cationic ion channels widely distributed in mammalian tissues. In general, the global genetic disruption of individual TRP channels result in phenotypes associated with impairment of a particular tissue and/or organ function. An exception is the genetic ablation of the TRP channel TRPM7, which results in early embryonic lethality.

Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models.

Mammalian sperm acquire fertilizing capacity in the female tract in a process called capacitation. At the molecular level, capacitation requires protein kinase A activation, changes in membrane potential and an increase in intracellular calcium. Inhibition of these pathways results in loss of fertilizing ability in vivo and in vitro.

TRPV3 channels mediate Ca²⁺ influx induced by 2-APB in mouse eggs.

Fertilization in mammals is initiated when a sperm fuses with a mature MII oocyte, also known as egg, and triggers a plethora of finely controlled processes identified as egg activation. The completion of all events of egg activation is driven by and depends on a series of repetitive calcium (Ca(2+)) increases (Ca(2+) oscillations), which rely on Ca(2+) influx from the extracellular media. Ca(2+) channels on the egg plasma membrane (PM) are thought to mediate this influx.

Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report.

Purpose: The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca(2+)) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro.

Methods: An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC- ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca(2+) release.

Dpy19l2-deficient globozoospermic sperm display altered genome packaging and DNA damage that compromises the initiation of embryo development.

We recently identified the DPY19L2 gene as the main genetic cause of human globozoospermia. Non-genetically characterized cases of globozoospermia were associated with DNA alterations, suggesting that DPY19L2-dependent globozoospermia may be associated with poor DNA quality. However the origins of such defects have not yet been characterized and the consequences on the quality of embryos generated with globozoospermic sperm remain to be determined.

Protein phospholipase C Zeta1 expression in patients with failed ICSI but with normal sperm parameters.

Purpose: This study was conducted to determine if expression of the testis-specific phospholipase C Zeta1 (PLCZ1) correlated with low success or fertilization failure after ICSI in patients with normal parameters after standard semen analysis (SA).

Methods: Couples <43 years with one or two failed or low fertilization ICSI cycles. Standard Semen Analysis (SA) was performed to determine sperm parameters in male partners, whereas females were evaluated for antral follicle counts (AFC), day 3 FSH levels and peak Estradiol (E2) levels.

TRPV3 channels mediate strontium-induced mouse-egg activation.

In mammals, calcium influx is required for oocyte maturation and egg activation. The molecular identities of the calcium-permeant channels that underlie the initiation of embryonic development are not established. Here, we describe a transient receptor potential (TRP) ion channel current activated by TRP agonists that is absent in TrpV3(-/-) eggs.

Metabolic activation of CaMKII by coenzyme A.

Active metabolism regulates oocyte cell death via calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated phosphorylation of caspase-2, but the link between metabolic activity and CaMKII is poorly understood. Here we identify coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte apoptosis by directly activating CaMKII. We found that CoA directly binds to the CaMKII regulatory domain in the absence of Ca(2+) to activate CaMKII in a calmodulin-dependent manner.