Disruption of female reproductive function by endotoxins

Endotoxemia can be caused by obesity, environmental chemical exposure, abiotic stressors, and bacterial infection. Circumstances that deleteriously impact intestinal barrier integrity can induce endotoxemia and controlled experiments have identified negative impacts of lipopolysaccharide (LPS; an endotoxin mimetic) on folliculogenesis, puberty onset, estrus behavior, ovulation, meiotic competence, luteal function and ovarian steroidogenesis. In addition, neonatal LPS exposures have transgenerational female reproductive impacts, raising concern about early life contacts to this endogenous reproductive toxicant. Aims of this review are to identify physiological stressors causing endotoxemia, to highlight potential mechanism(s) by which LPS compromises female reproduction, and identify knowledge gaps regarding how acute and/or metabolic endotoxemia influence(s) female reproduction

Leaky Gut’s Contribution to Inefficient Nutrient Utilization

There are a variety of situations in an animal’s life when nutrient utilization is reprioritized from productive towards agriculturally unproductive purposes. Two well-known examples that markedly reduce production are heat stress and ketosis. Decreased feed intake, experienced during both disorders, is unable to fully explain production losses. Additionally, both disorders are characterized by negative energy balance, body weight loss, inflammation, and liver fat accumulation. While the metabolism of ketosis and heat stress has been thoroughly studied for the last 40 years, the initial insult in the cascade of events ultimately reducing productivity in both heat-stressed and ketotic cows has not been identified. To that end, we have generated preliminary data strongly implicating a metabolic disruptor, endotoxin, as the underlying cause in each case

Identification of measures predictive of age of puberty onset in gilts

A potential indicator of female lifetime productivity in swine is age of puberty, when a gilt achieves her first behavioral estrus. Follicular activity, as determined by tertiary follicle development, in prepubertal gilts begins during postnatal day (PND) 75-115. The central hypothesis of this study is that gilts demonstrating tertiary follicle development earlier in life, assessed using vulva size as a proxy, achieve puberty earlier in life compared to counterparts of a similar age and weight that lack tertiary follicle development. The objectives of this project were to identify a developmental time point when variation in ovarian development exists and to determine if a relationship between the age prepubertal ovarian development and the age at onset of puberty exists. To accomplish this, 155 gilts of similar age (± 2 days) were weighed and vulva size measured on PND 75, 85, 95, 105 and 115. Vulva measures, including vulva width (VW), length (VL) and area (VA) were utilized as developmental proxies for follicular activity. At each time point, gilts (n = 10) were sacrificed and ovarian follicular activity recorded. In a subset of gilts (n = 105), estrus detection was conducted daily on PND days 126 to 200. Mean vulva area (VA) on PND 75, 85, 95, 105 and 115 was 596 ± 206, 683 ± 190, 864 ± 212, 1014 ± 228 and 1265 ± 252 mm2, respectively. Of the gilts demonstrating behavioral estrus, 28 were within PND 140-160, 36 between PND 161-180, 15 between PND 181-200, and 26 did not demonstrate estrus behavior within 200 days of age. All gilts euthanized at PND 75 lacked follicular activity as defined by having a minimum of two antral follicles per ovary, while 60%, 80%, 90% and 100% demonstrated follicular activity on PND 85, 95, 105, and 115, respectively. Body weight at PND 75 and VW at PND 115 were correlated to age at first estrus (P \u3c 0.05). Of the gilts whose VA was less than one standard deviation from the mean on PND 95 (i.e. \u3c 652 mm2), 31% and 50% demonstrated their first behavioral estrus by PND 180 and 200, respectively. However, of gilts whose VA was within or greater than one standard deviation of the mean (i.e. ≥ 652 mm2), 66% and 79% exhibited estrus prior to PND 180 and 200, respectively. These data support utilization of VA changes between 95 and 115 days of age as a useful tool to identify replacement gilts prior to puberty for inclusion into the sow herd

Methods for reproductive tract scoring as a tool for improving sow productivity

Improving sow lifetime productivity (SLP) is essential for maximizing farm profitability. Study objectives were to determine the accuracy for different vulva scoring methods in a commercial production system and to assess whether gilt reproductive tract scoring (evaluated by vulva width; VW) prior to puberty could serve as useful gilt selection criteria. To accomplish this objective, 958 prepubertal replacement gilts in a commercial system were evaluated at approximately 15 weeks of age. Gilt body weight was recorded in addition to four different methods to evaluate VW. Methods for VW assessment included digital caliper measurement (mm), visual evaluation and scoring by trained farm personnel (Farm Score; FS), and two methods using scoring tools (Vulva Score Method A and B; VSA and VSB, respectively) specifically calibrated from the VW distribution measured on gilts from previous studies. The VSA and FS methods assigned gilts to one of three categories (S, M, L and 1, 2, 3, respectively) whereas VSB classified gilts vulvas using a five-point scoring system (1 to 5). At 15-wk of age, a low proportion of variability in vulva size (27.8 ± 0.1 mm) could be explained by BW (62.2 ± 0.2 kg; R2 = 0.05). All three scoring methods were effective in categorizing gilts based upon VW, as the measured VW size within methods differed by score (P \u3c 0.01). The proportion of gilts achieving their first parity increased with score for VSA (64.7, 73.2, and 84.4%; P = 0.02), VSB (66.0, 71.7, 79.2, 76.4, and 84.2%; P = 0.02), and FS (67.2, 75.0, and 88.8%; P = 0.03), but VSA, VSB, and FS did not influence percentage of gilts achieving their second parity (P = 0.32, 0.29, and 0.30, respectively). Litter performance of gilts scored as M or L using VSA improved with an increased total born over two parities compared to those scored as S (23.96 vs. 26.38 pigs; P \u3c 0.01) as well as born alive (21.13 vs. 23.05 pigs; P \u3c 0.05). Results were similar for VSB, where scores 2-5 had greater total born (23.97 vs. 26.33 pigs; P \u3c 0.01) and born alive (21.11 vs. 23.02 pigs; P \u3c 0.05) through two parities compared to gilts scored 1. Using the FS method, total born pigs tended to be increased (P = 0.06) through two parities for gilts having a 2 or 3 vulva score compared to those scored as a 1. Collectively, assessing VW at approximately 15 wk of age may identify sows with improved productivity through two parities as breeding herd females

High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression

Insulin regulates ovarian phosphatidylinositol-3-kinase (PI3K) signaling, important for primordial follicle viability and growth activation. This study investigated diet-induced obesity impacts on: 1) insulin receptor (Insr) and insulin receptor substrate 1 (Irs1); 2) PI3K components (Kit ligand (Kitlg), kit (c-Kit), protein kinase B alpha (Akt1) and forkhead transcription factor subfamily 3 (Foxo3a)); 3) xenobiotic biotransformation (microsomal epoxide hydrolase (Ephx1), Cytochrome P450 isoform 2E1 (Cyp2e1), Glutathione S-transferase (Gst) isoforms mu (Gstm) and pi (Gstp)) and 4) microRNA’s 184, 205, 103 and 21 gene expression. INSR, GSTM and GSTP protein levels were also measured. Obese mouse ovaries had decreased Irs1, Foxo3a, Cyp2e1, MiR-103, and MiR-21 but increased Kitlg, Akt1, and miR-184 levels relative to lean littermates. These results support that diet-induced obesity potentially impairs ovarian function through aberrant gene expression.This is a mansuscript of an article published as Nteeba, J., J. W. Ross, J. W. Perfield Ii, and A. F. Keating. "High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression." Reproductive toxicology 42 (2013): 68-77. doi: 10.1016/j.reprotox.2013.07.026. Posted with permission.</p

A note on the evaluation of a beta-casein variant in bovine breeds by allele-specific PCR and relevance to beta-casomorphin

Journal articleTwo genetic variants of the bovine beta-casein gene (A(1) and B) encode a histidine residue at codon 67, resulting in potential liberation of a bioactive peptide, beta-casomorphin, upon digestion. An allele-specific PCR (AS-PCR) was evaluated to distinguish between the beta-casomorphin-releasing variants (A(1) and B) and the non-releasing variants. AS-PCR successfully distinguished P-casein variants in 41 of 42 animals as confirmed by sequence analysis. Overall, while the incidence of the homozygous A, and B animals (i.e., homozygous for the histidine residue; 21.4%) was lower than that for animals without the histidine residue (30.9% respectively), 69% of animals carried at least one allele for the histidine residue at codon 67.Teagasc; Enterprise Irelan

A single nucleotide polymorphism in the bovine beta-casein promoter region across different bovine breeds

Journal articleThe bovine β-casein (CSN2) gene has been shown to span a region of 8·5 kb, containing nine exons and eight intervening introns (Bonsing et al. 1988; Martin et al. 2002). The exons range in size from 24 to 498 bp; the introns, however, are much larger and account for 85% of the gene. Twelve genetic variants in the coding sequence of the β-casein gene have been reported (Farrell et al. 2004). The A2 allele of the β-casein gene has been associated with a higher milk production (Lin et al. 1986; Bech & Kristiansen, 1990) while the B variant has been associated with an increase in protein content and better cheesemaking properties (Marziali & Ng-Hang-Kwai, 1986). The β-casein gene codes for a protein of 209 amino acids with varying regions at codons 67, 106 and 122. The A1 variant differs from A2 at position 67, where a histidine replaces a proline (Lien et al. 1992). The β-casein A2 variant has histidine and the A3 variant has glycine at position 106 (Lien et al. 1992); the β-casein A2 variant has serine at position 122 and the β-casein B variant has arginine at this codon (Stewart et al. 1987; Damiani et al. 1992).Enterprise Ireland; Teagas