Ovarian, Hypophyseal and Hypothalamic Hormones Coordinate Mammary Gland Remodeling in Adult Lagostomus maximus: a Rodent that Shows Pseudo-Ovulation at Mid-Gestation

Adult female mammary glands go through extensive tissue remodeling during pregnancy, lactation and after the weaning of the neonates. Here we characterize mammary gland morphology of adult females of Lagostomus maximus, a hystricomorph rodent with a pseudo-ovulatory event at mid-gestation, and describe how the glandular tissue changes its architecture in response to variations of the hormonal environment. At mid-gestation, pseudo-ovulation is seen as an essential event increasing the number of secondary corpora lutea and thus rising the circulating levels of progesterone that help to maintain pregnancy to term. As a side effect, mammary gland development is favored early during the long-lasting pregnancy of L. maximus, preparing females for the nutritional need of fully developed pups in this k-strategist species

Challenging the Paradigms on the Origin, Specification and Development of the Female Germ Line in Placental Mammals

Most of our understanding on the origin, specification and development of the female germ line in placental mammals comes from studies in the laboratory mouse. The molecular pathway leading to the development and establishment of the female germ line in mouse has erected as the paradigm for placental mammals. It remains, however, largely unexplored whether the well-established mouse regulatory pathway is a common mechanism to other or all placental mammals. Discrete differences in mammals other than mouse reveal the existence of alternative mechanisms that challenge the currently accepted tenets on the origin and establishment of the mammalian female germinal reserve. Here, we will discuss the mouse framework in the light of emerging discrepancies seen in other placental mammals

Nutritional deficiency and placenta calcification underlie constitutive, selective embryo loss in pregnant South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

Plains vizcacha females are able to ovulate up to 800 oocytes per estrus cycle. However, just 10–12 embryos are implanted and only two of them, those located nearest the cervix, are gestated to term. Between 26 and 70 days post-coitum, a constitutive resorption occurs from the embryos located proximal to the ovary, extending progressively toward those distally implanted. Our previous studies on the dynamics of gestation in L. maximus, led us to hypothesize some kind of placental and nutritional insufficiency as the basis for the resorption process. We analyzed histology and arterial architecture of the reproductive tract in pregnant and non-pregnant females. Uterine horns are irrigated through the uterine artery, a branch of the internal iliac artery, in an ascending way from the cervix; segmental arteries irrigating the embryo vesicles become thinner as they approach the ovary. Contrast solution administered during angiographies accumulated in the placenta of embryos closest to cervix. Thus, blood stream favors the embryos nearest the cervix, indicating a gradual nutritional deficiency of those closest to the ovary. Besides, placenta becomes calcified early, at mid-gestation, during the resorption process. Finally, the detection of specialized endothelial venules and inflammatory cells suggest the concurrent participation of immunological processes in embryo vesicles undergoing resorption.Fil: Giacchino, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Claver, Juan Alberto. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Histología y Embriologías; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Lange, Fernando D.. Universidad Maimónides; ArgentinaFil: Gariboldi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Ferraris, Sergio Raúl. Universidad Maimónides; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentin

Transcriptome profiling of histone writers/erasers enzymes across spermatogenesis, mature sperm and pre-cleavage embryo: Implications in paternal epigenome transitions and inheritance mechanisms

Accumulating evidence points out that sperm carry epigenetic instructions to embryo in the form of retained histones marks and RNA cargo that can transmit metabolic and behavioral traits to offspring. However, the mechanisms behind epigenetic inheritance of paternal environment are still poorly understood. Here, we curated male germ cells RNA-seq data and analyzed the expression profile of all known histone lysine writers and erasers enzymes across spermatogenesis, unraveling the developmental windows at which they are upregulated, and the specific activity related to canonical and non-canonical histone marks deposition and removal. We also characterized the epigenetic enzymes signature in the mature sperm RNA cargo, showing most of them positive translation at pre-cleavage zygote, suggesting that paternally-derived enzymes mRNA cooperate with maternal factors to embryo chromatin assembly. Our study shows several histone modifying enzymes not described yet in spermatogenesis and even more, important mechanistic aspects behind transgenerational epigenetics. Epigenetic enzymes not only can respond to environmental stressors, but could function as vectors of epigenetic information and participate in chromatin organization during maternal-to-zygote transition

Population Genetics of Franciscana Dolphins (Pontoporia blainvillei): Introducing a New Population from the Southern Edge of Their Distribution

Due to anthropogenic factors, the franciscana dolphin, Pontoporia blainvillei, is the most threatened small cetacean on the Atlantic coast of South America. Four Franciscana Management Areas have been proposed: Espiritu Santo to Rio de Janeiro (FMA I), São Paulo to Santa Catarina (FMA II), Rio Grande do Sul to Uruguay (FMA III), and Argentina (FMA IV). Further genetic studies distinguished additional populations within these FMAs. We analyzed the population structure, phylogeography, and demographic history in the southernmost portion of the species range. From the analysis of mitochondrial DNA control region sequences, 5 novel haplotypes were found, totalizing 60 haplotypes for the entire distribution range. The haplotype network did not show an apparent phylogeographical signal for the southern FMAs. Two populations were identified: Monte Hermoso (MH) and Necochea (NC)+Claromecó (CL)+Río Negro (RN). The low levels of genetic variability, the relative constant size over time, and the low levels of gene flow may indicate that MH has been colonized by a few maternal lineages and became isolated from geographically close populations. The apparent increase in NC+CL+RN size would be consistent with the higher genetic variability found, since genetic diversity is generally higher in older and expanding populations. Additionally, RN may have experienced a recent split from CL and NC; current high levels of gene flow may be occurring between the latter ones. FMA IV would comprise four franciscana dolphin populations: Samborombón West+Samborombón South, Cabo San Antonio+Buenos Aires East, NC+CL+Buenos Aires Southwest+RN and MH. Results achieved in this study need to be taken into account in order to ensure the long-term survival of the species.Fil: Gariboldi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Tunez, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján; ArgentinaFil: Dejean, Cristina Beatriz. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas. Sección Antropología Biológica; ArgentinaFil: Failla, Mauricio. Fundación Cethus; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Negri, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Cappozzo, Humberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; Argentin

Editorial: Environmental factors affecting the germ line epigenome

Environmental influences on the male germ cell epigenome can promote male infertility. In recent years, epigenetic mechanisms regulating gene expression have thus raised much interest in reproductive biology, given the possibility of inherited acquired traits through the germ line . Environmental factors can induce changes in gene expression without altering DNA sequence through mechanisms including DNA methylation, histone post-translational modifications (PTMs), chromatin remodeling, and non-coding RNAs ). These mechanisms differentially signal chromatin states promoting open/transcription-permissive or closed/repressed states, or modifying the activity of regulatory elements such as enhancers and promoters . Diet, sedentary life, drug consumption or abuse, and exposure to endocrine disruptors may induce stable modifications of the mammalian germline and contribute to trans-generational effects. Therefore, much current research is focused on determining how environmental factors influence the germ cell epigenome, if they do, to encode transmissible, acquired traits. This Research Topic gathers several contributions highlighting possible environmental influences on male germ cell epigenome which can result in male infertility. The first article on this Topic (Faure et al., 2021) shows that in-utero exposure to metformin lowers male fertility without changes in sperm production or motility, likely promoted by hypermethylation of genomic DNA associated with a decreased expression of TET1. After birth, we learn through the study of Fenclová et al. (2022), that exposure to endocrine disruptors, such as bisphenols, through maternal milk promotes changes in H3 dimethylation and H2 phosphorylation. These epigenetic changes affect early embryonic development, the quality of germ cells, and thus spermatozoa, which could be the origin of male idiopathic infertility.Peer reviewe

FOXO3 and PTEN expression in the ovary of girls with extra-gonadal cancer with or without chemotherapy treatment prior to cryopreservation

Abstract Background FOXO3/pFOXO3 and PTEN expression is known to regulate the dormancy/activation of ovarian primordial follicles. How chemotherapy could influence the expression of FOXO3 and PTEN in pre- and post-menarcheal girls with extra-gonadal cancer remains unexplored. Methods Ovarian samples were collected from 27 girls suffering from extra-gonadal cancer. Of these, 8 patients had received chemotherapy before the time of sample collection. Ovarian tissue collected at the time of surgery was fixed in 10% formaldehyde for FOXO3/pFOXO3 and PTEN immunohistochemistry or immunofluorescence, or stored at -80 °C for Western blot, or preserved in RNA later for RT-PCR. Results PTEN was detected in a limited number of primordial follicle-enclosed oocytes in approximately fifty percent of the patients, regardless of whether they had received anti-cancer treatment or not. However, there was a significant decrease in PTEN detection in patients who underwent chemotherapy treatment prior to the retrieval of the sample. Both primordial follicle-enclosed oocytes that expressed FOXO3 and those that did not were identified in patients who were treated with chemotherapy and those who were not. FOXO3-positive primordial follicles exhibited either nuclear FOXO3 localization or cytoplasmic pFOXO3 localization. Furthermore, transitional primordial follicles that expressed nuclear FOXO3 and cytoplasmic pFOXO3 were also observed. Primary follicle-enclosed oocytes displayed cytoplasmic pFOXO3 localization, whereas in more advanced stages of folliculogenesis, the expression moved to the somatic stratum. No significant statistical differences were identified in the detection of FOXO3 and pFOXO3 in patients who had or had not received chemotherapy prior to sample collection. Conclusion Primordial follicles expressing and not expressing FOXO3 were equally present in both the ovaries of patients who underwent chemotherapy and those who did not. The expression of FOXO3 remained unaltered in response to chemotherapy treatment. Notably, the detection of PTEN was significantly reduced in the treated patients, thereby warranting in-depth investigation, given the limited sample size examined in the present study