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Assessment of Immunological Response and Impacts on Fertility Following Intrauterine Vaccination Delivered to Swine in an Artificial Insemination Dose.

ABSTRACT: To protect the health of sows and gilts, significant investments are directed toward the development of vaccines against infectious agents that impact reproduction. We developed an intrauterine vaccine that can be delivered with semen during artificial insemination to induce mucosal immunity in the reproductive tract. An in vitro culture of uterine epithelial cells was used to select an adjuvant combination capable of recruiting antigen-presenting cells into the uterus. Adjuvant polyinosinic:polycytidylic acid (poly I:C), alone or in combination, induced expression of interferon gamma, tumor necrosis factor alpha, and select chemokines. A combination adjuvant consisting of poly I:C, host defense peptide and polyphosphazene (Triple Adjuvant; TriAdj), which previously was shown to induce robust mucosal and systemic humoral immunity when administered to the uterus in rabbits, was combined with boar semen to evaluate changes in localized gene expression and cellular recruitment, in vivo. Sows bred with semen plus TriAdj had decreased ?? T cells and monocytes in blood, however, no corresponding increase in the number of monocytes and macrophages was detected in the endometrium. Compared to sows bred with semen alone, sows bred with semen plus TriAdj showed increased CCL2 gene expression in the epithelial layer. These data suggest that the adjuvants may further augment a local immune response and, therefore, may be suitable for use in an intrauterine vaccine. When inactivated porcine parvovirus (PPV) formulated with the TriAdj was administered to the pig uterus during estrus along with semen, we observed induction of PPV antibodies in serum but only when the pigs were already primed with parenteral PPV vaccines. Recombinant protein vaccines and inactivated PPV vaccines administered to the pig uterus during breeding as a primary vaccine alone failed to induce significant humoral immunity. More trials need to be performed to clarify whether repeated intrauterine vaccination can trigger strong humoral immunity or whether the primary vaccine needs to be administered via a systemic route to promote a mucosal and systemic immune response.

SUBMITTER: Hamonic G

PROVIDER: S-EPMC7267065 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Assessment of Immunological Response and Impacts on Fertility Following Intrauterine Vaccination Delivered to Swine in an Artificial Insemination Dose.

Hamonic Glenn G Pasternak J Alex JA Ng Siew Hon SH Fourie Kezia R KR Simko Olena M OM Deluco Brodie B Wilson Heather L HL

Frontiers in immunology 20200527

To protect the health of sows and gilts, significant investments are directed toward the development of vaccines against infectious agents that impact reproduction. We developed an intrauterine vaccine that can be delivered with semen during artificial insemination to induce mucosal immunity in the reproductive tract. An <i>in vitro</i> culture of uterine epithelial cells was used to select an adjuvant combination capable of recruiting antigen-presenting cells into the uterus. Adjuvant polyinosi ...[more]

PMID: 32536924

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Project description:BACKGROUND:Women with irregular menstruation should be considered to benefit from the ovarian stimulation. However, most literature did not separate ovulatory disorders from normal menstrual cycles. Our purpose was to assess the superiority of ovarian mild stimulation compared with the natural cycle in IUI for subfertile couples when the women with regular menstruation. METHODS:A retrospective study in a single medical center in which 2413 couples with 3573 IUI cycles were studied from 2013 to 2018. The results of IUI in natural cycles versus low-dose HMG induced cycles were analyzed. RESULTS:For young women (age < 35 years) with normal menstrual cycle, HMG induced ovulation combined with IUI can improve clinical pregnancy outcome (13.55% in two follicular induced cycles vs. 7.23% in natural cycles, p < 0.01); even if only one follicle was induced, the clinical pregnancy rate was increased to 10.32% (p < 0.01). When two growth follicles were induced in HMG cycles, a remarkable improvement of the live birthrate (10.28% vs. 5.91% in natural cycles, p < 0.05) was noted. Simultaneously, twin pregnancy rates were increased to 20.69% (p < 0.01). Twin pregnancies showed significantly increased risk of both ectopic pregnancy and preterm birth (p = 0.00 for both). For advanced women (age ≥ 35 years) with regular menstrual cycle, ovulation induction didn't improve clinical pregnancy and live birthrates, while age was the only relevant factor. CONCLUSIONS:Combining HMG induced ovulation and IUI can improve pregnancy outcome in young women with normal menstrual cycles. 1-2 follicles with diameter ≥ 14 mm served as the purpose of ovulation induction. Further, both twin and ectopic pregnancy rate in HMG cycles with two growth follicles were significantly higher than those in natural cycles were. Therefore, doctors must evaluate the risk before making choices and inform the patients to achieve the best results. For advanced women with normal menstrual cycles, natural IUI cycles were optional.

Project description:BackgroundConflicting results regarding alterations to sperm DNA methylation in cases of spermatogenesis defects, male infertility and poor developmental outcomes have been reported in humans. Bulls used for artificial insemination represent a relevant model in this field, as the broad dissemination of bull semen considerably alleviates confounding factors and enables the precise assessment of male fertility. This study was therefore designed to assess the potential for sperm DNA methylation to predict bull fertility.ResultsA unique collection of 100 sperm samples was constituted by pooling 2-5 ejaculates per bull from 100 Montbéliarde bulls of comparable ages, assessed as fertile (n = 57) or subfertile (n = 43) based on non-return rates 56 days after insemination. The DNA methylation profiles of these samples were obtained using reduced representation bisulfite sequencing. After excluding putative sequence polymorphisms, 490 fertility-related differentially methylated cytosines (DMCs) were identified, most of which were hypermethylated in subfertile bulls. Interestingly, 46 genes targeted by DMCs are involved in embryonic and fetal development, sperm function and maturation, or have been related to fertility in genome-wide association studies; five of these were further analyzed by pyrosequencing. In order to evaluate the prognostic value of fertility-related DMCs, the sperm samples were split between training (n = 67) and testing (n = 33) sets. Using a Random Forest approach, a predictive model was built from the methylation values obtained on the training set. The predictive accuracy of this model was 72% on the testing set and 72% on individual ejaculates collected from an independent cohort of 20 bulls.ConclusionThis study, conducted on the largest set of bull sperm samples so far examined in epigenetic analyses, demonstrated that the sperm methylome is a valuable source of male fertility biomarkers. The next challenge is to combine these results with other data on the same sperm samples in order to improve the quality of the model and better understand the interplay between DNA methylation and other molecular features in the regulation of fertility. This research may have potential applications in human medicine, where infertility affects the interaction between a male and a female, thus making it difficult to isolate the male factor.

Dataset Information

Assessment of Immunological Response and Impacts on Fertility Following Intrauterine Vaccination Delivered to Swine in an Artificial Insemination Dose.

Publications

Assessment of Immunological Response and Impacts on Fertility Following Intrauterine Vaccination Delivered to Swine in an Artificial Insemination Dose.

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