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Natália Teixeira Wnuk Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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André Felipe Almeida Figueiredo Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Talita de Oliveira Farias Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Marcos Rocha Gouvêa Brener Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Samyra Maria dos Santos Nassif Lacerda Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Vidyleison Neves Camargos Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Paulo Henrique Amaral Department of Physics, Institute of Exact Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Lídia Maria Andrade Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Maria Ivonete Nogueira Silva Department of Physics, Institute of Exact Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Roberta Araujo Lopes Department of Physiology and Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

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Raphael Escorsim Szawka Department of Physiology and Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

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Juan Carlos González Department of Physics, Institute of Exact Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Mauro Martins Teixeira Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Danielle da Glória de Souza Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Vivian Vasconcelos Costa Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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Guilherme Mattos Jardim Costa Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais – UFMG, Belo Horizonte, MG, Brazil

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In brief

Congenital ZIKV infection promotes alarming effects on male offspring's reproductive biology. This study showed the presence of the ZIKV antigen in the testis parenchyma, decreased testosterone levels, and sperm abnormalities in male offspring born to infected mothers.

Abstract

Infection with ZIKV during pregnancy is associated with fetal developmental problems. Although neurological issues are being explored more in experimental studies, limited research has focused on the reproductive health consequences for offspring born to infected mothers. In this context, this study aimed to assess the impact of ZIKV infection during pregnancy on the testes and sperm of adult male offspring. Female mice were intraperitoneally inoculated with a Brazil strain of ZIKV during the 5.5th day of embryonic gestation. The offspring were evaluated 12 weeks after birth to analyze cellular and molecular changes in the testes and sperm. A novel approach combining variable-angle spectroscopic ellipsometry and machine learning modeling was also introduced for sperm sample analysis. The study revealed the presence of ZIKV protein in the testis parenchyma of adult male offspring born to infected mothers. It was shown that the testes exhibited altered steroidogenesis and inflammatory mediators, in addition to significant issues with spermiogenesis that resulted in sperm with DNA fragmentation, head defects, and protamination failure. Additionally, sperm dielectric properties and artificial intelligence showed potential for rapid identification and classification of sperm samples from infected mice. These findings provide crucial insights into the reproductive risks for men born from ZIKV-infected pregnant women.

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Mathilde Daudon CNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France
Centre de recherche en reproduction et fertilité, Faculté de médecine vétérinaire, Université de Montréal, Saint Hyacinthe, Quebec, Canada

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Christelle Ramé CNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France

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Christopher A Price Centre de recherche en reproduction et fertilité, Faculté de médecine vétérinaire, Université de Montréal, Saint Hyacinthe, Quebec, Canada

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Joëlle Dupont CNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France

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Dairy cattle experience a period of infertility postpartum that is caused in part by the development of IGF1/insulin resistance. This study suggests that an adipokine, FNDC3A, reduces IGF1-dependent glycolysis and may contribute to postpartum infertility.

Abstract

Dairy cows go through a period of subfertility after parturition, triggered in part by a disruption of energy homeostasis. The mobilization of body fat alters the secretion of adipokines, which have been shown to impact ovarian function. Fibronectin type III domain-containing 3A (FNDC3A) is a recently discovered adipokine-myokine, and FNDC3A mRNA abundance in subcutaneous adipose tissue is increased postpartum in cattle. In this study, we hypothesized that FNDC3A may compromise granulosa cell function in cattle and investigated this using a well-established in vitro cell culture model. Here, we demonstrate the presence of FNDC3A protein associated with extracellular vesicles in follicular fluid and in plasma, suggesting an endocrine role for this adipokine. FNDC3A protein and mRNA was also detected in the bovine ovary (cortex, granulosa and theca cells, cumulus, oocyte and corpus luteum). Abundance of FNDC3A mRNA in granulosa cells from small follicles was increased by in vitro treatment with the adipokines leptin and TNF but not by visfatin, resistin, adiponectin, chemerin or IGF1. Addition of recombinant FNDC3A at physiological doses (10 ng/mL) to granulosa cells decreased IGF1-dependent progesterone but not estradiol secretion and IGF1-dependent lactate secretion and abundance of GLUT3 and GLUT4 mRNA. This concentration of FNDC3A increased cell viability, abundance of mRNA encoding a putative receptor FOLR1, and increased phosphorylation of Akt. Collectively, these data suggest that FNDC3A may regulate folliculogenesis in cattle by modulating IGF1-dependent granulosa cell steroidogenesis and glucose metabolism.

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Marlyne Squatrito Laboratory of Biology of Tumor and Development, GIGA-Cancer, University of Liège, Liège, Belgium

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Julie Vervier Laboratory of Biology of Tumor and Development, GIGA-Cancer, University of Liège, Liège, Belgium
Department of Obstetrics and Gynecology, Hôpital de la Citadelle, University of Liège, Liège, Belgium

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Jules Bindels Laboratory of Biology of Tumor and Development, GIGA-Cancer, University of Liège, Liège, Belgium

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Laëtitia Bernet Laboratory of Biology of Tumor and Development, GIGA-Cancer, University of Liège, Liège, Belgium

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Silvia Blacher Laboratory of Biology of Tumor and Development, GIGA-Cancer, University of Liège, Liège, Belgium

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Michelle Nisolle Department of Obstetrics and Gynecology, Hôpital de la Citadelle, University of Liège, Liège, Belgium

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Carine Munaut Laboratory of Biology of Tumor and Development, GIGA-Cancer, University of Liège, Liège, Belgium

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In brief

The impact of adenomyosis on reproductive health needs to be fully understood. By using a murine model, this study provides novel insights into the nuanced mechanisms associated with fertility challenges and offers a foundation for targeted interventions.

Abstract

This study investigates the intricate relationship between adenomyosis and reproductive health using a murine model, offering novel insights into this prevalent gynecological disorder. Adenomyosis, characterized by the invasive growth of endometrial tissue into the myometrium, is believed to negatively impact fertility. However, the challenge lies in disentangling this influence, as adenomyosis often coexists with other gynecological diseases. A tamoxifen-induced mice model presents a significant advantage by enabling the specific study of adenomyosis, devoid of confounding influences of concurrent gynecological diseases such as endometriosis. Focusing exclusively on adenomyosis, our study aims to elucidate pathogenic mechanisms underlying fertility issues, focusing on estrous cyclicity, ovarian follicle development, and overall fertility. Our findings uncover disruptions in estrous cyclicity, characterized by an increased duration of time spent in the estrus phase in adenomyosis-induced mice. These disturbances are potentially linked to observed compromised folliculogenesis and the remarkable reduction in litter number and size in mice affected by adenomyosis. Moreover, this study unveils potential drivers of subfertility such as progesterone resistance and altered endometrial receptivity. Within the uteri of mice with adenomyosis, reduced expression of the progesterone receptor and a decreased expression of two implantation-related markers (HoxA10 and integrin β3) were observed. This comprehensive examination sheds light on the nuanced complexities of adenomyosis-associated reproductive challenges, providing a foundation for targeted interventions in addressing fertility issues related to this disease.

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Baobao Zhao College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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Heqiang Li College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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Han Zhang College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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Xinrui Lan College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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Xingchen Ren College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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Liangyi Zhang College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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Huiming Ma Key Laboratory of Fertility Preservation and Maintenance (Ministry of Education), Ningxia Medical University, Yinchuan, Ningxia, China

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Yong Zhang College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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Yongsheng Wang College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China
Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, PR China

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In brief

HSP90AA1 is a ubiquitous molecular chaperone that can resist cellular stress, such as oxidative stress and apoptosis, and mediate the efficacy and protein folding of normal cells during heat stress, as well as many other functions. This study further reveals the role of HSP90AA1 in bovine oocyte maturation and early embryonic development.

Abstract

HSP90AA1, a highly abundant and ubiquitous molecular chaperone, plays important roles in various cellular processes including cell cycle control, cell survival, and hormone signaling pathways. In this study, we investigated the functions of HSP90AA1 in bovine oocyte and early embryo development. We found that HSP90AA1 was expressed at all stages of development, but was mainly located in the cytoplasm, with a small amount distributed in the nucleus. We then evaluated the effect of HSP90AA1 on the in vitro maturation of bovine oocytes using tanespimycin (17-AAG), a highly selective inhibitor of HSP90AA1. The results showed that inhibition of HSP90AA1 decreased nuclear and cytoplasmic maturation of oocytes, disrupted spindle assembly and chromosome distribution, significantly increased acetylation levels of α-tubulin in oocytes and affected epigenetic modifications (H3K27me3 and H3K27ac). In addition, H3K9me3 was increased at various stages during early embryo development. Finally, the impact of HSP90AA1 on early embryo development was explored. The results showed that inhibition of HSP90AA1 reduced the cleavage and blastocyst formation rates, while increasing the fragmentation rate and decreasing blastocyst quality. In conclusion, HSP90AA1 plays a crucial role in bovine oocyte maturation as well as early embryo development.

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Gretchen M Rosado Magee-Womens Research Institute, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Ana Martinez-Marchal Magee-Womens Research Institute, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Mariela Faykoo-Martinez Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

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Melissa M Holmes Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada

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Miguel Angel Brieño-Enríquez Magee-Womens Research Institute, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

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Recently, we described that in the naked mole rat ovary it is possible to study the ovarian reserve and the mitotic expansion of the germ cell postnatally. Herein, we show oocyte in vitro maturation and in vitro germ cell expansion using the same ovary.

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L Kirsten Senn Department of Animal Science, University of Tennessee Institute of Agriculture, University of Tennessee, Knoxville, Tennessee, USA

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Katheryn D Peterson Department of Animal Science, University of Tennessee Institute of Agriculture, University of Tennessee, Knoxville, Tennessee, USA

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J Lannett Edwards Department of Animal Science, University of Tennessee Institute of Agriculture, University of Tennessee, Knoxville, Tennessee, USA

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Rebecca R Payton Department of Animal Science, University of Tennessee Institute of Agriculture, University of Tennessee, Knoxville, Tennessee, USA

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Daniel J Mathew Department of Animal Science, University of Tennessee Institute of Agriculture, University of Tennessee, Knoxville, Tennessee, USA

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In brief

Standard in vitro produced (IVP) bovine embryo culture media limit embryonic development. Culturing IVP bovine embryos in standard IVP bovine embryo culture media conditioned with oviduct and/or endometrial cells improves blastocyst formation and reduces the time to formation.

Abstract

In vitro embryo production in cattle greatly impacts blastomere biochemistry, embryo rate of development and pre- and post-transfer survival. In vivo, the bovine embryo migrates through the oviduct isthmus before entering the uterus on approximately day 4 of development where it remains unattached within the uterine lumen until day 20 of gestation. During this time, the embryo is sequentially exposed to oviduct followed by endometrial secretions that support embryonic development. Considering this, we tested the effect of culturing in vitro produced (IVP) bovine embryos sequentially in oviduct epithelial- (OEp; days 1–3) followed by endometrial epithelial- (EEp) or EEp and fibroblast cell (EEp/F; days 4–8)-conditioned media on embryonic development using a time-lapse monitoring system. Compared to control, culturing IVP embryos in EEp- or EEp/F-conditioned media without prior culture in OEp-conditioned media increased blastocyst formation (P < 0.05) and reduced the time to blastocyst formation (P < 0.05). Culturing IVP bovine embryos in OEp-conditioned media followed by EEp- or EEp/F-conditioned media, however, had the greatest impact on embryo developmental kinetics and increased morula and blastocyst formation (P < 0.05) and reduced time to formation (P < 0.05). Day 8 blastocyst cell numbers, diameter and quality were not significantly different, although, blastocyst quality scores were less (indicative of better quality) for all cell-conditioned media compared to control. In conclusion, IVP bovine embryo development may be improved using a sequential embryo culture system involving bovine oviduct followed by endometrial cell-conditioned media.

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Aimé Silva Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos, Facultad de Medicina, Universidad de Buenos Aires

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Alicia Motta Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos, Facultad de Medicina, Universidad de Buenos Aires

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Adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS) are frequently associated with abnormal placental functions. This review explores the involvement of proliferator-activated receptors (PPARs) in these processes, to gain molecular insights into abnormal pregnancy conditions associated with PCOS.

Abstract

Polycystic ovary syndrome (PCOS) is one of the major endocrine disorders affecting women during their reproductive ages.Given its association with other pathologies, such as insulin resistance, metabolic syndrome, type 2 diabetes, and obesity, women with PCOS could present high-risk pregnancies, including a high abortion rate, implantation failure, an increased risk of gestational diabetes, preeclampsia, and intrauterine growth restriction. These adverse pregnancy outcomes are often attributed, at least in part, to defects in placental functions. Peroxisome proliferator-activated receptors (PPARs) are important transcription factors that participate in various placental pathways, regulating the expression of genes involved in lipid and glucose metabolism and inflammation. Furthermore, PPARs have been shown to play a role in placental development and function. Taking together this evidence, the present review focuses on the role of PPARs in placental tissue and discusses their implications in the pregnancy outcomes commonly associated with the presence of PCOS. In addition, the main treatments frequently employed have also been discussed.

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João Vitor Alcantara da Silva Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil

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Jessica Ispada Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil

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Ricardo Perecin Nociti Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil

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Aldcejam Martins da Fonseca Junior Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil

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Camila Bruna de Lima Département des Sciences Animales, Laval University, Canada

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Erika Cristina dos Santos Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil

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Marcos Roberto Chiaratti Department of Genetics and Evolution, Federal University of Sao Carlos, Sao Carlos, SP, Brazil

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Marcella Pecora Milazzotto Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil

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In brief

Pyruvate metabolism is one of the main metabolic pathways during oocyte maturation. This study demonstrates that pyruvate metabolism also regulates the epigenetic and molecular maturation in bovine oocytes.

Abstract

Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus–oocyte complexes were cultured in vitro for 24 h, considering three experimental groups: Control (IVM medium only), DCA (IVM supplemented with sodium dichloroacetate, a stimulant of pyruvate oxidation into acetyl-CoA), or IA (IVM supplemented with sodium iodoacetate, a glycolysis inhibitor). The results revealed significant alterations in oocyte metabolism in both treatments, promoting the utilization of lipids as an energy source. These changes during IVM affected the dynamics of H3K9ac, subsequently influencing the oocyte's transcriptional activity. In the DCA and IA groups, a total of 148 and 356 differentially expressed genes were identified, respectively, compared to the control group. These findings suggest that modifications in pyruvate metabolism trigger the activation of metabolic pathways, particularly lipid metabolism, changing acetyl-CoA availability and H3K9ac levels, ultimately impacting the mRNA content of in vitro matured bovine oocytes.

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Chad S Driscoll Department of Animal Science, Developmental Epigenetics Laboratory, Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan, USA

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Jaehwan Kim Department of Animal Science, Developmental Epigenetics Laboratory, Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan, USA
Department of Animal Sciences, University of Missouri, Columbia, Missouri, USA

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Mohamed Ashry Department of Animal Science, Developmental Epigenetics Laboratory, Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan, USA

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Jason G Knott Department of Animal Science, Developmental Epigenetics Laboratory, Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan, USA

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Transcription factor AP2 gamma (TFAP2C) is a well-established regulator of the trophoblast lineage in mice and humans, but a handful of studies indicate that TFAP2C may play an important role in pluripotency. Here, we hypothesize and provide new evidence that TFAP2C functions as an activator of trophoblast and pluripotency genes during preimplantation embryo development.

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Carolina Marvaldi Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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Felisa Herrero Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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Clare Johnson Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA

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Julieta Aylen Schander Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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Fernando Correa Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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Maximiliano Cella Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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Julieta Aisemberg Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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Ana María Franchi Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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Heather Bradshaw Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA

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Manuel Luis Wolfson Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

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In brief

The cervix plays a crucial role not only in the maintenance of pregnancy but also during delivery, when it undergoes extensive changes. This study highlights the involvement of the endocannabinoidome in cervical remodeling, emphasizing its relevance in the shift from a nonpregnant to pregnant state and its potential contribution to preterm delivery in inflammatory contexts.

Abstract

During pregnancy, the main role of the cervix is to isolate the fetus from outside pathogens and maintain the relatively closed system of uterine gestation. Conversely, toward the end of pregnancy, the cervix must be remodeled to increase flexibility and allow the delivery. This process is called cervical remodeling and dysregulation of the process plays a role in premature delivery. The endocannabinoidome plays an important role in several reproductive events; however, its function on cervical tissue throughout pregnancy is poorly understood. The goal of this study was to evaluate the presence and participation of the endocannabinoidome in lipopolysaccharide (LPS)-induced cervical changes. Therefore, we evaluated key components of the endocannabinoidome in cervical tissue from nonpregnant mice and pregnant mice with and without LPS treatment. Using mass spectrometric analysis, we found an increase in anandamide and 2-arachidonoylglycerol in the cervix of pregnant mice when compared to nonpregnant mice. We have also found a reduction in FAAH protein expression in these tissues. Furthermore, when treated with LPS, we observed a reduction in the cervical immunostaining with anti-CB1 and anti-CB2 antibodies. Likewise, using cervix explants from pregnant mice, we found that LPS significantly increased cervical metalloprotease activity and cyclooxygenase 2, which were subsequently modulated by cannabinoid receptor antagonists. Collectively, our findings suggest that an LPS-induced imbalance of cervix endocannabinoidome likely contributes to premature cervical remodeling, which is part of the key components that contribute to premature delivery.

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