Reductions in the number of mid-sized antral follicles are associated with markers of premature ovarian senescence in dairy cows

High-producing dairy cows are subfertile; however, the mechanisms responsible for the decreased fertility are unknown. The aim of the present study was to test the hypothesis that culled dairy cows (4\u20138 years old) characterised by \u2018Lo\u2019 ovaries (i.e. those with <10 mid-antral follicles) are affected by premature ovarian senescence. Cows in which both ovaries were \u2018Lo\u2019 ovaries represented 5% of the total population analysed, and exhibited reduced ovarian size (P < 0.001) and increased perifollicular stroma (P < 0.05) compared with age-matched controls (i.e. cows in which both ovaries had >10 mid-antral follicles; \u2018Hi\u2019 ovaries). The total number of follicles, including healthy and atretic primordial, primary, secondary and small antral follicles, was lower in Lo ovaries (P < 0.01). Interestingly, the primordial follicle population in Lo ovaries was lower (P < 0.05) than in the control. Finally, the follicular fluid of mid-antral follicles from Lo ovaries had reduced oestradiol and anti-M\ufcllerian hormone levels (P < 0.05), but increased progesterone concentrations (P < 0.05). Together, these data account for the reduced fertility of cows with Lo ovaries and are in agreement with previous observations that oocytes isolated from Lo ovaries have reduced embryonic developmental competence. Cows with a specific Lo ovary condition may represent a suitable model to address the causes of low fertility in high-yielding dairy cows, as well as the condition of premature ovarian aging in single-ovulating species

Expression of progesterone receptor membrane component-1 in bovine reproductive system during estrous cycle

Several reports suggest the participation of progesterone receptor membrane component 1 (PGRMC1) in progesterone signaling in the reproductive system. This study aimed at investigating the presence and localization of PGRMC1 in bovine ovary, oviduct and uterus, during the follicular and luteal phases of the estrous cycle. In the ovary, PGRMC1 has been detected in surface germinal epithelium, granulosa cells, theca cells and in the germinal vesicle of the oocytes at all stages of folliculogenesis. In the corpus luteum the expression of PGRMC1 was influenced by the stage of the estrous cycle. In the oviducts and in the uterus horns, PGRMC1 was immunolocalized in the luminal epithelium, in the muscle layer cells and in the endothelial cells. In the uterus, PGRMC1 was intensely localized also in the glandular endometrium. However, in the oviducts and in the uterus horns, the localization of PGRMC1 was independent on the stage of the estrous cycle and on whether evaluating the ipsilateral or the contralateral organ. In conclusion, the present immunohistochemical study showed that PGRMC1 is located in various compartments of the bovine female reproductive organs. With the exception of the corpora lutea, PGRMC1 localization showed similar pattern during different stages of the estrous cycle

The endothelial nitric oxide synthase/nitric oxide system is involved in the defective quality of bovine oocytes from low mid-antral follicle count ovaries

In a previous survey concerning cows of reproductive age, we demonstrated that oocytes isolated from ovaries with 10 medium antral follicles (High ovaries, Hi). The aim of the present study was to evaluate whether a defective endothelial nitric oxide synthase/nitric oxide (eNOS/NO) system and vasculature in healthy medium antral follicles is likely to reduce oocyte competence from Lo ovaries. Thus, experiments were conducted to: (1) immunolocalize eNOS protein during folliculogenesis; (2) quantify eNOS protein/vasculature in the follicle wall; and (3) verify if NO donor, S-nitroso acetyl penicillamine (SNAP) administration during in vitro maturation affects developmental competence of oocytes isolated from Lo ovaries. Endothelial-NOS protein was detected in granulosa and theca cells, as well as in blood vessels from primordial to antral follicles. Quantitative analysis indicated that in medium antral follicles from Lo ovaries, eNOS protein expression and vasculature were reduced (P < 0.05). The addition of SNAP improved blastocyst and hatching rates of oocytes from Lo ovaries, promoting a percentage similar to oocytes from Hi ovaries, and reduced the percentage of apoptotic nuclei in in vitro-produced blastocysts (P < 0.05). Results from our study suggest that in bovine ovaries with low mid antral follicle number, a defective eNOS/NO system is related to a reduced follicle vasculature and may impact oocyte quality, thus inducing a premature decline of fertility

Renal outcome in patients with congenital anomalies of the kidney and urinary tract.

15openopenSanna-Cherchi S; Ravani P; Corbani V; Parodi S; Haupt R; Piaggio G; Innocenti ML; Somenzi D; Trivelli A; Caridi G; Izzi C; Scolari F; Mattioli G; Allegri L; Ghiggeri GM.Sanna Cherchi, S; Ravani, P; Corbani, V; Parodi, S; Haupt, R; Piaggio, G; Innocenti, Ml; Somenzi, D; Trivelli, A; Caridi, G; Izzi, C; Scolari, Francesco; Mattioli, G; Allegri, L; Ghiggeri, G. M

Dietary fatty acids on subcutaneous adipose tissue modulation in transition dairy goats

The goal of the present study was to evaluate the metabolic and immune response of peripartal dairy goats to dietary supplementation with fish oil or stearic acid. 15 multiparous alpine dairy goats were involved in the trial. Starting from the last week of gestation until 3 weeks after kidding date the experimental diets, based on alfalfa and mix hays and a concentrate mix, were added either with protected fish oil (FO) or with stearic acid (ST). Feed intake, body weight, energy balance, milk production and composition were measured weekly. Adipose tissue biopsies were performed on day -7, 7 and 21 relative to kidding date and samples were immediately fixed in formalin, paraffin embedded and Hematoxilin Eosin stained. The results discussed in the present work are relative to a subsample of 8 goats, representative of the two experimental groups. Hematological and histological data were analyzed by a Generalized Estimating Equation (GEE) in IBM SPSS 19.0 was used. Production parameters were analyzed by a MIXED repeated model in SAS 9.2. No differences were observed between FO and ST in milk production, BCS, weight, dry matter intake and milk components except for a higher milk protein percentage in the 7 to 21 d period for ST. BHB serum content was higher in ST overall the experiment, whereas NEFA and ALAT serum content were higher at day 7 in FO compared to ST (P < 0.08). ALAT was higher also at day 21 in FO. Treatment had no effect on blood cellular component except for WBC in FO group, where a significant decrease at 7 d was observed. WBC and HCM parameters were in the physiological range for dairy goats during transition period. Histologic adipose tissue analysis revealed a significant decreased adipocytes surface between -7 and 21 d in ST, whereas in FO the adipocyte surface reduction was related to the -7 to 7 d interval reaching a plateau until day 21. The EB pattern and the NEFA serum content at 7d in particular for FO are well correlated with histologic observations indicating goats were using fat depots to cope their negative energy balance. NEFA levels did not confirm the histological evidence at day 21 for ST suggesting a possible different action on subcutaneous adipose tissue during time. Results suggest a modulation in lipid storage management during peripartal negative energy balance by saturated vs. unsaturated dietary fatty acid supplementation that did not affect production levels of goats

Contribution of copy number variants (CNVs) to congenital, unexplained intellectual and developmental disabilities in Lebanese patients

International audienceBackground: Chromosomal microarray analysis (CMA) is currently the most widely adopted clinical test for patients with unexplained intellectual disability (ID), developmental delay (DD), and congenital anomalies. Its use has revealed the capacity to detect copy number variants (CNVs), as well as regions of homozygosity, that, based on their distribution on chromosomes, indicate uniparental disomy or parental consanguinity that is suggestive of an increased probability of recessive disease. Results: We screened 149 Lebanese probands with ID/DD and 99 healthy controls using the Affymetrix Cyto 2.7 M and SNP6.0 arrays. We report all identified CNVs, which we divided into groups. Pathogenic CNVs were identified in 12.1% of the patients. We review the genotype/phenotype correlation in a patient with a 1q44 microdeletion and refine the minimal critical regions responsible for the 10q26 and 16q monosomy syndromes. Several likely causative CNVs were also detected, including new homozygous microdeletions (9p23p24.1, 10q25.2, and 8p23.1) in 3 patients born to consanguineous parents, involving potential candidate genes. However, the clinical interpretation of several other CNVs remains uncertain, including a microdeletion affecting ATRNL1. This CNV of unknown significance was inherited from the patient's unaffected-mother; therefore, additional ethnically matched controls must be screened to obtain enough evidence for classification of this CNV. Conclusion: This study has provided supporting evidence that whole-genome analysis is a powerful method for uncovering chromosomal imbalances, regardless of consanguinity in the parents of patients and despite the challenge presented by analyzing some CNVs

The Gene Ontology knowledgebase in 2023

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed