Use of model systems to understand the etiology of fragile X-associated primary ovarian insufficiency (FXPOI)

Fragile X-associated primary ovarian insufficiency (FXPOI) is among the family of disorders caused by the expansion of a CGG repeat sequence in the 5' untranslated region of the X-linked gene FMR1. About 20% of women who carry the premutation allele (55 to 200 unmethylated CGG repeats) develop hypergonadotropic hypogonadism and cease menstruating before age 40. Some proportion of those who are still cycling show hormonal profiles indicative of ovarian dysfunction. FXPOI leads to subfertility and an increased risk of medical conditions associated with early estrogen deficiency. Little progress has been made in understanding the etiology of this clinically significant disorder. Understanding the molecular mechanisms of FXPOI requires a detailed knowledge of ovarian FMR1 mRNA and FMRP's function. In humans, non-invasive methods to discriminate the mechanisms of the premutation on ovarian function are not available, thus necessitating the development of model systems. Vertebrate (mouse and rat) and invertebrate (Drosophila melanogaster) animal studies for the FMR1 premutation and ovarian function exist and have been instrumental in advancing our understanding of the disease phenotype. For example, rodent models have shown that FMRP is highly expressed in oocytes where it is important for folliculogenesis. The two premutation mouse models studied to date show evidence of ovarian dysfunction and, together, suggest that the long repeat in the transcript itself may have some pathological effect quite apart from any effect of the toxic protein. Further, ovarian morphology in young animals appears normal and the primordial follicle pool size does not differ from that of wild-type animals. However, there is a progressive premature decline in the levels of most follicle classes. Observations also include granulosa cell abnormalities and altered gene expression patterns. Further comparisons of these models are now needed to gain insight into the etiology of the ovarian dysfunction. Premutation model systems in non-human primates and those based on induced pluripotent stem cells show particular promise and will complement current models. Here, we review the characterization of the current models and describe the development and potential of the new models. Finally, we will discuss some of the molecular mechanisms that might be responsible for FXPOI

COVID-19 and human reproduction: A pandemic that packs a serious punch

The COVID-19 pandemic has led to a worldwide health emergency that has impacted 188 countries at last count. The rapid community transmission and relatively high mortality rates with COVID-19 in modern times are relatively unique features of this flu pandemic and have resulted in an unparalleled global health crisis. SARS-CoV-2, being a respiratory virus, mainly affects the lungs, but is capable of infecting other vital organs, such as brain, heart and kidney. Emerging evidence suggests that the virus also targets male and female reproductive organs that express its main receptor ACE2, although it is as yet unclear if this has any implications for human fertility. Furthermore, professional bodies have recommended discontinuing fertility services during the pandemic such that reproductive services have also been affected. Although increased safety measures have helped to mitigate the propagation of COVID-19 in a number of countries, it seems that there is no predictable timeline to containment of the virus, a goal likely to remain elusive until an effective vaccine becomes available  and widely distributed across the globe. In parallel, research on reproduction has been postponed for obvious reasons, while diagnostic tests that detect the virus or antibodies against it are of vital importance to support public health policies, such as social distancing and our obligation to wear masks in public spaces. This review aims to provide an overview of critical research and ethics issues that have been continuously emerging in the field of reproductive medicine as the COVID-19 pandemic tragically unfolds. Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: Assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CCR9: C-C Motif Chemokine Receptor 9; CDC: Centers for Disease Control and Prevention; COVID-19: Coronavirus disease 2019; Ct: Cycle threshold; CXCR6: C-X-C Motif Chemokine Receptor 6; ELISA: enzyme-linked immunosorbent assay; ESHRE: European Society of Human Reproduction and Embryology; ET: Embryo transfer; FSH: Follicle Stimulating Hormone; FFPE: formalin fixed paraffin embedded; FYCO1: FYVE And Coiled-Coil Domain Autophagy Adaptor 1; IFFS: International Federation of Fertility Societies; IUI: Intrauterine insemination; IVF: In vitro fertilization; LH: Luteinizing Hormone; LZTFL1: Leucine Zipper Transcription Factor Like 1; MAR: medically assisted reproduction services; MERS: Middle East Respiratory syndrome; NGS: Next Generation Sequencing; ORF: Open Reading Frame; PPE: personal protective equipment; RE: RNA Element; REDa: RNA Element Discovery algorithm; RT-PCR: Reverse=trascriptase transcriptase-polymerase chain reaction; SARS: Severe acute respiratory syndrome; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SLC6A20: Solute Carrier Family 6 Member 20; SMS: Single Molecule Sequencing; T: Testosterone; TMPRSS2: transmembrane serine protease 2; WHO: World Health Organization; XCR1: X-C Motif Chemokine Receptor. © 2021 Informa UK Limited, trading as Taylor & Francis Group

Efeito da temperatura e do fotoperíodo sobre o desenvolvimento do aparelho reprodutor de rã-touro (Rana catesbeiana Shaw, 1802) Effect of the temperature and the photoperiod on the development of bullfrog (Rana catesbeiana Shaw, 1802) reproduction apparel

Foram avaliados os efeitos da temperatura e do fotoperíodo sobre a maturação sexual de rãs-touro pesando 94,22 g ± 12,03, mantidas durante trinta dias em temperaturas de 20, 23, 26, 29, 32 e 35°C, com fotoperíodo de 12/12 horas de luz/horas de escuridão (h L/E). A temperatura afetou os pesos do corpo gorduroso e do fígado, os quais variaram de acordo com modelos quadráticos, estimando-se maiores pesos de corpo gorduroso a 27,27°C e de fígado a 26,81°C. Estimaram-se ovários mais pesados a 28,36°C e ovidutos mais pesados a 28,77°C. Temperatura afetou a maturação sexual das rãs, avaliada por índices numéricos. Num experimento mais longo, rãs com peso médio inicial de 95,31 ± 8,46 g foram submetidas à combinação das temperaturas de 26 e 29°C com os fotoperíodos de 8/16, 12/12 e 16/8 h L/E, até atingirem a maturidade gonadal. Temperatura interagiu com fotoperíodo em seus efeitos sobre o desenvolvimento dos órgãos reprodutivos de rã-touro. Temperatura afetou a relação diâmetro do abdômen/distância entre os olhos, com maiores valores calculados para 26°C. Verificou-se que os maiores diâmetros dos ovócitos são obtidos a uma temperatura de 26°C, com fotoperíodo de 12,6/11,4 h L/E.<br>The effects of the temperature and of the photoperiod on the bull frog sexual maturation of frogs weighing 94.22 g ± 12.03, maintained for thirty days under temperatures of 20, 23, 26, 29, 32 and 35°C, with photoperiod of 12/12 hours of light/hours of darkness (h L/D), were evaluated. Temperature affected the weights of the fat body and liver, that varied according to quadratic models, and higher weights of fat body at 27.27°C and of liver at 26.81°C were considered. The ovaries heavier than 28.36°C and oviducts heavier than 28.77°C were estimated. Temperature affected the sexual maturation of the frogs, evaluated by numeric indexes. In a longer experiment, frogs with initial weight of 95.31 g ± 8.46, were submitted to the combination of the temperatures of 26.0 and 29.0°C with photoperiods of 8/16, 12/12 and 16/8 h L/D, until they reach the gonadal maturity. Temperature interacted with photoperiod in its effects on the development of the reproductive organs of bullfrog. Temperature affected the diameter of the abdomen/distance relation between the eyes, with higher values calculated for 26°C. It was considered that the highest ovocites diameters are obtained under a temperature of 26.0°C, with photoperiod of 12.6/11.4 h L/D