The cGAS-STING pathway is an modifier of genomic instability syndromes.

Mutations in genes involved in DNA damage repair (DDR) often lead to premature aging syndromes. While recent evidence suggests that inflammation, alongside mutation accumulation and cell death, may drive disease phenotypes, its precise contribution to pathophysiology remains unclear. Here, by modeling Ataxia Telangiectasia (A-T) and Bloom Syndrome in the African turquoise killifish ( ), we replicate key phenotypes of DDR syndromes, including infertility, cytoplasmic DNA fragments, and reduced lifespan.

The direct effect of SARS-CoV-2 virus vaccination on human ovarian granulosa cells explains menstrual irregularities.

Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital sign", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality.

Pigment epithelium-derived factor expression and role in follicular development.

Research Question: What is the involvement of pigment epithelium-derived factor (PEDF), expressed in granulosa cells, in folliculogenesis?

Design: mRNA expression of PEDF and other key factors [Cyp19, anti-Müllerian hormone receptor (AMHR) and vascular endothelial growth factor (VEGF)] in mice follicles was examined in order to typify the expression of PEDF in growing follicles and in human primary granulosa cells (hpGC), and to follow the interplay between PEDF and the other main players in folliculogenesis: FSH and AMH.

Results: mRNA expression of PEDF increased through folliculogenesis, although the pattern differed from that of the other examined genes, affecting the follicular angiogenic and oxidative balance. In hpGC, prolonged exposure to FSH stimulated the up-regulation of PEDF mRNA.

Planned oocyte cryopreservation: a systematic review and meta-regression analysis.

Background: Awareness of the age-related decline in fertility potential has increased the popularity of planned oocyte cryopreservation (POC). However, data regarding outcomes of POC, including rates of women returning to thaw oocytes, as well as pregnancy and live birth rates, are scarce and based mostly on small case series.

Objective And Rationale: POC was defined as cryopreservation exclusively for prevention of future age-related fertility loss.

IVF outcomes pre- and post-anti-COVID-19 vaccination - Are there any differences?

Since the beginning of the SARS-CoV-2 pandemic, there have been rising concerns about the virus's possible ability to affect male and female fertility. Although effective vaccines were introduced and the vaccination rate of the general population is high, some reproductive-age individuals are still hesitant to receive the vaccine, because of an unestablished belief that the vaccine might impair fertility. In this single-center retrospective study, encompassing data from 387 medical files of in-vitro fertilization (IVF) patients we compared IVF cycle outcomes and sperm characteristics in vaccinated couples before and after vaccination, as well as between vaccinated patients and a control group of individuals who were neither vaccinated nor infected with COVID-19 before or during the cycles.

Stain-Free Sperm Analysis and Selection for Intracytoplasmic Sperm Injection Complying with WHO Strict Normal Criteria.

This multi-center study evaluated a novel microscope system capable of quantitative phase microscopy (QPM) for label-free sperm-cell selection for intracytoplasmic sperm injection (ICSI). Seventy-three patients were enrolled in four in vitro fertilization (IVF) units, where senior embryologists were asked to select 11 apparently normal and 11 overtly abnormal sperm cells, in accordance with current clinical practice, using a micromanipulator and 60× bright field microscopy. Following sperm selection and imaging via QPM, the individual sperm cell was chemically stained per World Health Organization (WHO) 2021 protocols and imaged via bright field microscopy for subsequent manual measurements by embryologists who were blinded to the QPM measurements.

Impact of pre-treatment in GnRH-antagonist cycles triggered with GnRH agonist on reproductive outcomes.

Objective: Pre-treatment (PT) therapies in IVF are known to be used as pre-stimulation modality to improve cycle outcomes. This study aims to assess whether PT in GnRH antagonist cycles triggered with GnRH-agonist impact oocyte maturation response.

Methods: Data were retrospectively collected for patients who underwent GnRH antagonist cycle with agonist triggering with and without PT.

PGT pregnancies have a similar risk for post-partum complications as naturally conceived pregnancies.

Research Question: Do preimplantation genetic testing (PGT) pregnancies have higher post-partum complications compared with naturally conceived pregnancies?

Design: Retrospective cohort study conducted in 2008-2020 at the Shaare Zedek Medical Center (SZMC), including all patients aged 18-45 years old who conceived following PGT with a singleton live birth >24 weeks. Data were collected from computerized hospital databases and patient files. There were two control groups: (i) pregnancies following IVF-ICSI (intracytoplasmic sperm injection); (ii) four neighbourhood controls for each case delivery (two women delivered before and two after) of women with naturally conceived pregnancies.

Clinical outcome of planned oocyte cryopreservation at advanced age.

Purpose: To report outcome of planned oocyte cryopreservation (POC) in the first 8 years of this treatment in our center.

Methods: A retrospective study in a university-affiliated medical center.

Results: A total of 446 women underwent POC during 2011-2018.

The Role of PEDF in Reproductive Aging of the Ovary.

Reproductive aging is characterized by a decline in ovarian function and in oocytes' quantity and quality. Pigment epithelium-derived factor (PEDF), a pivotal player in ovarian angiogenic and oxidative balance, was evaluated for its involvement in reproductive aging. Our work examines the initial stage of reproductive aging in women and mice, and the involvement of PEDF in the process.

Loss of heterochromatin and retrotransposon silencing as determinants in oocyte aging.

Mammalian oocyte quality reduces with age. We show that prior to the occurrence of significant aneuploidy (9M in mouse), heterochromatin histone marks are lost, and oocyte maturation is impaired. This loss occurs in both constitutive and facultative heterochromatin marks but not in euchromatic active marks.

GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch.

Background: G protein-coupled receptors (GPCRs) usually regulate cellular processes via activation of intracellular signaling pathways. However, we have previously shown that in several cell lines, GqPCRs induce immediate inactivation of the AKT pathway, which leads to JNK-dependent apoptosis. This apoptosis-inducing AKT inactivation is essential for physiological functions of several GqPCRs, including those for PGF2α and GnRH.

Pigment epithelium-derived factor negates oxidative stress in mouse oocytes.

Molecular changes, caused by various environmental factors, affect the quality and developmental potential of oocytes. Oxidative stress (OS) is a major factor involved in various gynecologic disorders and/or in aging. Recent studies suggest that elevated reactive oxygen species (ROS) hamper oocyte quality and future embryonic development.

Expanded clinical validation of Haploseek for comprehensive preimplantation genetic testing.

Purpose: We previously developed Haploseek, a method for comprehensive preimplantation genetic testing (PGT). However, some key features were missing, and the method has not yet been systematically validated.

Methods: We extended Haploseek to incorporate DNA from embryo grandparents and to allow testing of variants on chromosome X or in regions where parents share common haplotypes.

Pigment epithelium derived factor as a novel multi-target treatment for uterine fibroids.

Research Question: Does recombinant pigment epithelium derived factor (PEDF) have potential in treating uterine fibroids?

Design: In-vitro models that used human leiomyoma and Eker rat uterine leiomyoma (ELT-3) cell lines. The ELT-3 cell line was used to examine cellular targets after adding recombinant PEDF to the culture media. Athymic nude female mice were used as an in-vivo model.

Pigment epithelium-derived factor (PEDF) negates hyperandrogenic PCOS features.

Polycystic ovary syndrome (PCOS), one of the most common female endocrine disorder, is a prevalent cause of infertility. Hyperandrogenism is a key feature in PCOS and is correlated with increased expression of VEGF and cytokines in the ovaries. We have previously shown that pigment epithelium-derived factor (PEDF), an endogenous protein, presents potent anti-angiogenic and anti-inflammatory activities in the ovary and negates the effects of cytokines and VEGF.

Elucidating the role of pigment epithelium-derived factor (PEDF) in metabolic PCOS models.

PCOS is the most common endocrinopathy in women; associated with obesity and insulin resistance (IR). IR leads to accumulation of advanced-glycation-end-products (AGEs) and their receptor, RAGE. PCOS patients have increased levels of vascular endothelial growth factor (VEGF), interleukin 6/8 (IL-6/8) and anti-Mϋllerian-hormone (AMH).

Gq-Induced Apoptosis is Mediated by AKT Inhibition That Leads to PKC-Induced JNK Activation.

Background/aims: Gq protein-coupled receptors (GqPCRs) regulate various cellular processes including mainly proliferation and differentiation. In a previous study, we found that in prostate cancer cells, the GqPCR of GnRH induces apoptosis by reducing the PKC-dependent AKT activity and elevating JNK phosphorylation. Since it was thought that GqPCR induces mainly activation of AKT, we undertook to examine how general is this phenomenon and understand its signaling.

Hysteroscopic removal of retained products of conception following first trimester medical abortion.

Study Objective: To investigate the use of operative hysteroscopy instead of traditional curettage in women with retained products of conception (RPOC) following first trimester medical abortion, with the aim of reducing post-operative intrauterine adhesions.

Design: Retrospective study.

Setting: Gynecology department in a University affiliated hospital.