Comparison of clinical artificial oocyte activation protocols on mouse egg activation and embryo development.

Artificial oocyte activation (AOA) with Ca2+ ionophores is an experimental procedure that benefits patients who fail to obtain fertilized eggs. However, the impact of non-physiological Ca2+ increases on cellular events involved in egg-embryo transition and early development remains poorly understood. Using the mouse model, this study compares common Ca2+ ionophore protocols applied in clinical practice - one or two exposures to A23187 or a single exposure to ionomycin - focusing on embryonic development and cellular events associated with egg activation.

Could probiotics be used as a novel therapeutic approach to alleviate the reproductive and neurobehavioral side effects of sertraline? A study in male mice.

There are still few studies that have investigated the impact of sertraline (SE) on fertility, as well as adjuvant treatments that alleviate its side effects. Thus, the present study aimed to investigate the impact of SE on reproductive and neurobehavior parameters and verify whether the probiotic Lactobacillus rhamnosus alleviates the side effects of SE. After carrying out a dose-response study with SE, experiment II was conducted.

Physiological and pathological aspects of epididymal sperm maturation.

In mammals, sperm that leave the testes are nonfunctional and require a complex post-testicular maturation process to acquire their ability to recognize and fertilize the egg. The crucial maturation changes that provide sperm their fertilizing capability occur while passing through the epididymis. Due to the widespread use of assisted reproductive technologies to address male infertility, there has been a significant decrease in research focusing on the mechanisms underlying the maturation process over the past decades.

Elucidating metformin action on the ovary and fertility in healthy mice.

In Brief: The hypoglycemic drug metformin has shown reproductive effects in women, although its mechanism of action is not fully understood. In this study, we demonstrate the direct effects of metformin on the ovary of healthy mice, with no alterations in fertility.

Abstract: Metformin is a hypoglycemic drug widely used in type-2 diabetes (T2D) patients.

A side-by-side comparison of different capacitation media in developing mouse sperm fertilizing ability.

To acquire the ability to fertilize the egg, mammalian spermatozoa must undergo a series of changes occurring within the highly synchronized and specialized environment of the female reproductive tract, collectively known as capacitation. In an attempt to replicate this process in vitro, various culture media for mouse sperm were formulated over the past decades, sharing a similar overall composition but differing mainly in ion concentrations and metabolic substrates. The widespread use of the different media to study the mechanisms of capacitation might hinder a comprehensive understanding of this process, as the medium could become a confounding variable in the analysis.

Membrane potential hyperpolarization: a critical factor in acrosomal exocytosis and fertilization in sperm within the female reproductive tract.

Hyperpolarization of the membrane potential (Em), a phenomenon regulated by SLO3 channels, stands as a central feature in sperm capacitation-a crucial process conferring upon sperm the ability to fertilize the oocyte. studies demonstrated that Em hyperpolarization plays a pivotal role in facilitating the mechanisms necessary for the development of hyperactivated motility (HA) and acrosomal exocytosis (AE) occurrence. Nevertheless, the physiological significance of sperm Em within the female reproductive tract remains unexplored.

Beneficial effects of metformin on mice female fertility after a high-fat diet intake.

Female fertility is highly dependent on energy balance. High fat diet (HFD) intake entails a risk of infertility and ovulatory disorders. Considering the increase in the prevalence of overweight and obesity over the last decades, it is crucial to understand the mechanisms involved in overweight-associated infertility.

Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility.

Mammalian fertilization is a complex process involving a series of successive sperm-egg interaction steps mediated by different molecules and mechanisms. Studies carried out during the past 30 years, using a group of proteins named CRISP (Cysteine-RIch Secretory Proteins), have significantly contributed to elucidating the molecular mechanisms underlying mammalian gamete interaction. The CRISP family is composed of four members (i.

Capacitation-Induced Mitochondrial Activity Is Required for Sperm Fertilizing Ability in Mice by Modulating Hyperactivation.

To become fully competent to fertilize an egg, mammalian sperm undergo a series of functional changes within the female tract, known as capacitation, that require an adequate supply and management of energy. However, the contribution of each ATP generating pathway to sustain the capacitation-associated changes remains unclear. Based on this, we investigated the role of mitochondrial activity in the acquisition of sperm fertilizing ability during capacitation in mice.

Effect of ulipristal acetate on gene expression profile in endometrial cells in culture and upon post-ovulatory administration in fertile women.

Purpose: To analyse the effect of ulipristal acetate (UPA) as emergency contraception (EC) on the gene expression of human endometrial cell line (HEC-1A) and endometrium from fertile women treated with UPA after ovulation.

Materials And Methods: HEC-1A cells were treated with UPA, and endometrial tissue from four healthy women was collected in cycles before, during and 2 months after post-ovulation pill intake. Ovulation and luteal phase were monitored, and endometrial biopsies were obtained at day LH + 7 in each cycle.

Pharmacological Inactivation of CatSper Blocks Sperm Fertilizing Ability Independently of the Capacitation Status of the Cells: Implications for Non-hormonal Contraception.

Cation channel of sperm (CatSper), the main sperm-specific Ca channel, plays a key role in mammalian fertilization, and it is essential for male fertility, becoming an attractive target for contraception. Based on this, in the present work, we investigated the effects of CatSper inactivation on and sperm fertilizing ability and the mechanisms underlying such effects. Exposure of cauda epididymal mouse sperm to different concentrations (1-20 μM) of the potent CatSper inhibitor HC-056456 (HC) during capacitation showed no effects on sperm viability but significantly affected Ca entry into the cells, progressive motility, protein tyrosine phosphorylation, induced acrosome reaction, and hyperactivation, as well as the sperm's ability to fertilize cumulus oocyte complexes and zona-free eggs.

Metabolic syndrome and male fertility disorders: Is there a causal link?

Infertility is a global health problem affecting 10-15% of couples in reproductive age. Recent studies have provided growing evidence supporting that lifestyle factors can affect male fertility through alterations in endocrine profiles, spermatogenesis and/or sperm function. One of these critical factors could be the change in the food intake behavior in modern societies that produces metabolic alterations.

Functional redundancy and compensation: Deletion of multiple murine Crisp genes reveals their essential role for male fertility.

Mammalian Cysteine-RIch Secretory Protein (CRISP) family includes four members present in sperm and reported to regulate Ca channels and fertilization. Based on our previous observations using single knockouts models and suggesting the existence of functional compensation among CRISP proteins, we investigated their relevance for male fertility by generating multiple Crisp gene mutants by CRISPR/Cas9 technology. Whereas targeting of Crisp1 and Crisp3 yielded subfertile males with early embryo developmental defects, the same deletion in zygotes from fertile Crisp2 .

Evolutionary analysis of genes coding for Cysteine-RIch Secretory Proteins (CRISPs) in mammals.

Background: Cysteine-RIch Secretory Proteins (CRISP) are expressed in the reproductive tract of mammalian males and are involved in fertilization and related processes. Due to their important role in sperm performance and sperm-egg interaction, these genes are likely to be exposed to strong selective pressures, including postcopulatory sexual selection and/or male-female coevolution. We here perform a comparative evolutionary analysis of Crisp genes in mammals.

Association between high-fat diet feeding and male fertility in high reproductive performance mice.

The increasing worldwide prevalence of metabolic syndrome (MetS), especially in younger populations, is a risk factor for fertility disorders. However, a direct correlation of MetS with male infertility still remains unclear. In this work, we evaluated whether MetS has a negative impact on fertility of hybrid male mice with high reproductive performance.

Mechanisms involved in the contraceptive effects of ulipristal acetate.

The use of emergency contraception (EC) methods is increasing worldwide as it constitutes an effective way to prevent unplanned pregnancy after unprotected sexual intercourse. During the last decade, ulipristal acetate (UPA), a selective progesterone receptor modulator, has emerged as the most effective EC pill, and it is now recommended as first-line hormonal treatment for EC in several countries. Its principal mechanism of action involves inhibition or delay of follicular rupture, but only when administered during the follicular phase before the luteinizing hormone (LH) peak.

Compensatory endocytosis occurs after cortical granule exocytosis in mouse eggs.

Compensatory endocytosis (CE) is one of the primary mechanisms through which cells maintain their surface area after exocytosis. Considering that in eggs massive exocytosis of cortical granules (CG) takes place after fertilization, the aim of this study was to evaluate the occurrence of CE following cortical exocytosis in mouse eggs. For this purpose, we developed a pulse-chase assay to detect CG membrane internalization.

Relevance of CRISP proteins for epididymal physiology, fertilization, and fertility.

Background: The molecular mechanisms involved in the acquisition of mammalian sperm fertilizing ability are still poorly understood, reflecting the complexity of this process.

Objectives: In this review, we describe the role of Cysteine RIch Secretory Proteins (CRISP1-4) in different steps of the sperm journey to the egg as well as their relevance for fertilization and fertility.

Materials And Methods: We analyze bibliography reporting the phenotypes of CRISP KO mice models and combine this search with recent findings from our team.

A single post-ovulatory dose of ulipristal acetate impairs post-fertilization events in mice.

Ulipristal acetate (UPA) is a selective progesterone receptor modulator used for emergency contraception that has proven to be highly effective in preventing pregnancy when taken up to 120 h after unprotected sexual intercourse. Even though it may act mainly by delaying or inhibiting ovulation, additional effects of UPA on post-fertilization events cannot be excluded. Therefore, the aim of this study was to determine whether a single post-ovulatory dose of UPA could prevent pregnancy using the mouse as a pre-clinical model.

Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4.

Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with sperm during maturation and play different roles in fertilization. However, males lacking each of these molecules individually are fertile, suggesting compensatory mechanisms between these homologous proteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO) mice and examined their reproductive phenotype.

Tyrosine phosphorylation signaling regulates Ca entry by affecting intracellular pH during human sperm capacitation.

Capacitation is a mandatory process for the acquisition of mammalian sperm fertilization competence and involves the activation of a complex and still not fully understood system of signaling pathways. Under in vitro conditions, there is an increase in both protein tyrosine phosphorylation (pTyr) and intracellular Ca levels in several species. In human sperm, results from our group revealed that pTyr signaling can be blocked by inhibiting proline-rich tyrosine kinase 2 (PYK2).

Ceramide-1-phosphate has protective properties against cyclophosphamide-induced ovarian damage in a mice model of premature ovarian failure.

Study Question: Is ceramide-1-phosphate (C1P) an ovarian protective agent during alkylating chemotherapy?

Summary Answer: Local administration of C1P drastically reduces ovarian damage induced by cyclophosphamide (Cy) via protection of follicular reserve, restoration of hormone levels, inhibition of apoptosis and improvement of stromal vasculature, while protecting fertility, oocyte quality and uterine morphology.

What Is Known Already: Cancer-directed therapies cause accelerated loss of ovarian reserve and lead to premature ovarian failure (POF). Previous studies have demonstrated that C1P regulates different cellular processes including cell proliferation, cell migration, angiogenesis and apoptosis.