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All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

JAZ repressors of metabolic defense promote growth and reproductive fitness in Arabidopsis

Plant immune responses mediated by the hormone jasmonoyl-L-isoleucine (JA-Ile) are metabolically costly and often linked to reduced growth. Although it is known that JA-Ile activates defense responses by triggering the degradation of JASMONATE ZIM DOMAIN (JAZ) transcriptional repressor proteins, expansion of the JAZ gene family in vascular plants has hampered efforts to understand how this hormone impacts growth and other physiological tasks over the course of ontogeny. Here, we combined mutations within the 13-member Arabidopsis JAZ gene family to investigate the effects of chronic JAZ deficiency on growth, defense, and reproductive output. A higher-order mutant (jaz decuple, jazD) defective in 10 JAZ genes (JAZ1–7, -9, -10, and -13) exhibited robust resistance to insect herbivores and fungal pathogens, which was accompanied by slow vegetative growth and poor reproductive performance. Metabolic phenotypes of jazD discerned from global transcript and protein profiling were indicative of elevated carbon partitioning to amino acid-, protein-, and endoplasmic reticulum body-based defenses controlled by the JA-Ile and ethylene branches of immunity. Resource allocation to a strong defense sink in jazD leaves was associated with increased respiration and hallmarks of carbon starvation but no overt changes in photosynthetic rate. Depletion of the remaining JAZ repressors in jazD further exaggerated growth stunting, nearly abolished seed production and, under extreme conditions, caused spreading necrotic lesions and tissue death. Our results demonstrate that JAZ proteins promote growth and reproductive success at least in part by preventing catastrophic metabolic effects of an unrestrained immune response.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

JAZ proteins promote growth and reproduction by restraining transcriptional programs that link primary and specialized metabolism

Plants constantly experience attack from surrounding organisms. Because they cannot escape from the environment, plants have evolved a sophisticated immune system to defend themselves against pests and pathogens. However, mounting a defense response is often accompanied by a decrease in growth. The antagonistic relationship between growth and defense has been interpreted as the plant's “dilemma” of how to distribute limited resources between these two fundamental processes. Jasmonic acid (JA) and its derivatives are a class of lipid‐derived hormones that mediate plant immunity against insect herbivores and necrotrophic pathogens, as well as growth, reproduction, and several other physiological processes. JA is perceived by its receptor CORONATINE INSENSITIVE 1 (COI1), which mediates the degradation of the JASMONATE ZIM DOMAIN (JAZ) transcriptional repressors by the 26S proteasome. JAZ degradation releases JA‐responsive transcription factors such as MYC2 from repression, thereby initiating JA responses. Despite the importance of JA in mediating growth‐defense tradeoffs, the mechanism by which JA effects carbon resource allocation between growth and defense is poorly understood. In this study we demonstrate strong constitutive activation of JA signaling pathway in an Arabidopsis mutant ( jazD ) that lacks ten members of JASMONATE ZIM DOMAIN (JAZ) family proteins. This mutant displayed elevated defense against insect herbivores, stunted growth of vegetative tissues, as well as compromised seed reproduction. Metabolic phenotypes of jazD discerned from global protein and transcript profiling were indicative of elevated carbon allocation to protein‐ and amino acid‐based defense compounds. The strong defense sink in jazD leaves was linked to increased respiration and hallmarks of carbon starvation, whereas area‐based photosynthetic efficiency was unaffected. These findings establish a role for JAZ proteins in promoting growth and reproductive success through restraint of transcriptional programs that link primary metabolism to specialized metabolism. Our data suggest that JAZs adjust growth‐defense balance to match anticipated changes in carbon availability, potentially avoiding detrimental effects of carbon limitation that arise during growth‐to‐defense transitions. Support or Funding Information This research was funded by the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science, US Department of Energy through grant DE–FG02–91ER20021. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Guo, Qiang↗
DOE OSTI2018

A Vitis vinifera basic helix-loop-helix transcription factor enhances plant cell size, vegetative biomass and reproductive yield

Strategies for improving plant size are critical targets for plant biotechnology to increase vegetative biomass or reproductive yield. To improve biomass production, a codon-optimized helix–loop–helix transcription factor (VvCEB1 opt ) from wine grape was overexpressed in Arabidopsis thaliana resulting in significantly increased leaf number, leaf and rosette area, fresh weight and dry weight. Cell size, but typically not cell number, was increased in all tissues resulting in increased vegetative biomass and reproductive organ size, number and seed yield. Ionomic analysis of leaves revealed the VvCEB1 opt- overexpressing plants had significantly elevated, K, S and Mo contents relative to control lines. Increased K content likely drives increased osmotic potential within cells leading to greater cellular growth and expansion. To understand the mechanistic basis of VvCEB1 opt action, one transgenic line was genotyped using RNA-Seq mRNA expression profiling and revealed a novel transcriptional reprogramming network with significant changes in mRNA abundance for genes with functions in delayed flowering, pathogen–defence responses, iron homeostasis, vesicle-mediated cell wall formation and auxin-mediated signalling and responses. Direct testing of VvCEB1 opt- overexpressing plants showed that they had significantly elevated auxin content and a significantly increased number of lateral leaf primordia within meristems relative to controls, confirming that cell expansion and organ number proliferation were likely an auxin-mediated process. VvCEB1 opt overexpression in Nicotiana sylvestris also showed larger cells, organ size and biomass demonstrating the potential applicability of this innovative strategy for improving plant biomass and reproductive yield in crops.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Contrasting anther glucose–6–phosphate dehydrogenase activities between two bean varieties suggest an important role in reproductive heat tolerance

Common beans (Phaseolus vulgaris) are highly sensitive to elevated temperatures, and rising global temperatures threaten bean production. Plants at the reproductive stage are especially susceptible to heat stress due to damage to male (anthers) and female (ovary) reproductive tissues, with anthers being more sensitive to heat. Heat damage promotes early tapetal cell degradation, and in beans this was shown to cause male infertility. In this study, we focus on understanding how changes in leaf carbon export in response to elevated temperature stress contribute to heat-induced infertility. We hypothesize that anther glucose-6-phosphate dehydrogenase (G6PDH) activity plays an important role at elevated temperature and promotes thermotolerance. To test this hypothesis, we compared heat-tolerant and susceptible common bean genotypes using a combination of phenotypic, biochemical, and physiological approaches. Our results identified changes in leaf sucrose export, anther sugar accumulation and G6PDH activity and anther H 2 O 2 levels and antioxidant-related enzymes between genotypes at elevated temperature. Further, anther respiration rate was found to be lower at high temperature in both bean varieties. Overall, our results support the hypothesis that enhanced male reproductive heat tolerance involves changes in the anther oxidative pentose phosphate pathway, which supplies reductants to critical H 2 O 2 scavenging enzymes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Reproductive intentions among HIV-negative gay and bisexual men initiating pre-exposure prophylaxis in the Sustainable Health Center Implementation pre-exposure prophylaxis pilot study, 2014–2016

Introduction We assessed reproductive intentions and associated characteristics among men enrolled in the Sustainable Health Center Implementation pre-exposure prophylaxis (PrEP) Pilot (SHIPP) Study. Methods We analyzed baseline data from 1275 men who self-identified as gay or bisexual and participated in the SHIPP study. SHIPP was a cohort study of PrEP implementation in five community health centers in Chicago, Jackson, Philadelphia, and Washington, D.C. conducted from 2014 to 2016. Participants completed audio computer-assisted self-interviews querying intentions to have a child in the future. We estimated the association between participants’ reproductive intentions and their characteristics using Poisson regression models. Results Approximately 47% of participants indicated their intentions to have a child. Black/non-Hispanic (aPR = 1.40; 95% CI: 1.10–1.78) and other/non-Hispanic participants (aPR = 1.40; 95% CI: 1.01–1.93) were more likely to report intentions to have a child than white/non-Hispanic participants. Participants were less likely to report intentions to have children as age increased (18–29 years, reference group; 30–39 years, aPR = 0.80, 95% CI: 0.64–0.99; 40–49 years, aPR = 0.49, 95% CI: 0.33–0.72; 50+ years, aPR = 0.07, 95% CI: 0.02–0.21). Conclusions Clinicians offering PrEP to black and other/non-Hispanic gay and bisexual men should assess their reproductive intentions as family-planning counseling may be an opportunity to introduce PrEP to HIV-negative gay and bisexual men.

Immunology↗
DOE OSTI2022

Co-Exposure of Nanopolystyrene and Other Environmental Contaminants—Their Toxic Effects on the Survival and Reproduction of Enchytraeus crypticus

Plastics in all shapes and sizes have become widespread across ecosystems due to intense anthropogenic use. As such, they can interact with other contaminants that accumulate in the terrestrial environment, such as pharmaceuticals, metals or nanomaterials (NMs). These interactions can potentiate combined toxic effects in the exposed soil organisms, with hazardous long-term consequences to the full ecosystem. In the present study, a terrestrial model species, Enchytraeus crypticus (oligochaeta), was exposed through contaminated soil with nanopolystyrene (representative of nanoplastics (NPls)), alone and in combination with diphenhydramine (DPH, representative of pharmaceuticals), silver nitrate (AgNO3, representative of metals) and vanadium nanoparticles (VNPs, representative of NMs). AgNO3 and VNPs decreased E. crypticus reproduction at 50 mg/kg, regardless of the presence of NPls. Moreover, at the same concentration, both single and combined VNP exposures decreased the E. crypticus survival. On the other hand, DPH and NPls individually caused no effect on organisms’ survival and reproduction. However, the combination of DPH (10 and 50 mg/kg) with 300 mg NPls/kg induced a decrease in reproduction, showing a relevant interaction between the two contaminants (synergism). Our findings indicate that the NPls can play a role as vectors for other contaminants and can potentiate the effects of pharmaceuticals, such as DPH, even at low and sub-lethal concentrations, highlighting the negative impact of mixtures of contaminants (including NPls) on soil systems.

Mendes, Luís A. (ORCID:0000000245738290)↗
DOE OSTI2018

Estimation of the HIV-1 infection rate and the basic reproductive ratio

This paper proposes and analyzes an alternative method to estimate important parameters of the HIV-1 infection: the infection rate and the basic reproductive ratio (in the presence and absence of the immune response). These parameters are of great relevance, impacting on the infection chronicity. The method consists in comparing clinical data in the chronic stage with predicted equilibrium points of a mathematical model which describes the dynamics of HIV-1 in the acute infection phase. The fact that the method uses only clinical data relating to the chronic stage is an important aspect since most patients are diagnosed at this stage, and thus only have data available for this stage. A comparison between the proposed method and other estimation methods, as well as between numerical simulations, is presented and the results are quite satisfactory. In addition, by applying the proposed method for data of 31 patients, we estimate the basic reproductive ratio in the presence of the immune response and the HIV-1 infection rate for which we obtained a median of 1.95 (IQR 0.55) and 1.96×10{sup −5} mm{sup 3} virions{sup −1} day{sup −1} (IQR 3.52×10{sup −5}), respectively.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Let it rip: The mechanics of self-bisection in asexual planarians determines their population reproductive strategies

Asexual freshwater planarians reproduce by transverse bisection (binary fission) into two pieces. This process produces a head and a tail, which fully regenerate within 1-2 weeks. How planarians split into two offspring - using only their musculature and substrate traction – is a challenging biomechanics problem. We found that three different species, Dugesia japonica, Girardia tigrina and Schmidtea mediterranea, have evolved three different mechanical solutions to self-bisect. Using time lapse imaging of the fission process, we quantitatively characterize the main steps of division in the three species and extract the distinct and shared key features. Across the three species, planarians actively alter their body shape, regulate substrate traction, and use their muscles to generate tensile stresses large enough to overcome the ultimate tensile strength of the tissue. Moreover, we show that how each planarian species divides dictates how resources are split among its offspring. This ultimately determines offspring survival and reproductive success. Furthermore, heterospecific differences in the mechanics of self-bisection of individual worms explain the observed differences in the population reproductive strategies of different planarian species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea

Background: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. Methods: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Results: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66–1.13] compared to 0.60 [0.49–0.73], 0.46 [0.38–0.56] and 0.62 [0.51–0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14–1.84] compared to 1.25 [0.99–1.58], 1.06 [0.85–1.32] and 0.86 [0.69–1.08]) and alcohol consumption (1.22 [1.01–1.48] compared to 1.10 [0.90–1.33], 1.15 [0.96–1.38], and 1.07 [0.91–1.26]). Conclusion: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Is selfing a reproductive assurance promoting polyploid establishment? Reduced fitness, leaky self‐incompatibility and lower inbreeding depression in neotetraploids

Premise Newly formed polyploids face significant obstacles to persistence and population establishment because of fitness costs of intercytotype mating. Selfing provides the opportunity to escape mate limitation, enabling production of new individuals and increasing the likelihood of fixation of new polyploid lineages. Still, association between self‐compatibility and polyploidy is not always clear. We compared self‐incompatibility and inbreeding depression in neotetraploids and their diploid progenitor to explore the direct effects of whole genome duplications on self‐incompatibility and the implications of ploidy‐driven changes for polyploid establishment. Methods Outcross and self‐pollinations were performed in diploids and synthetic neotetraploids of Jasione maritima var. maritima , and reproductive success was measured through fruit and seed production and seed germination. Self‐ and outcross offspring were grown under controlled conditions, and plant performance was measured through several fitness parameters. Results Neotetraploids showed an overall lower performance than diploids. Reproductive success was negatively affected by selfing in both cytotypes. However, greater variation in the expression of self‐incompatibility was observed in neotetraploids; additionally, developmental and physiological parameters were not affected by selfing on neotetraploids, with an overall similar fitness of outcrossed and selfed individuals, resulting in lower inbreeding depression indexes. Conclusions Neotetraploids might have benefited from selfing at initial stages after their formation. Genome duplications resulted in leaky self‐incompatibility, enabling the production of offspring under minority cytotype disadvantage with similar fitness as outcrossed offspring. Our results support theoretical assumptions that selfing might be important for neopolyploid establishment, although changes in self‐incompatibility might not be abrupt.

Siopa, Catarina↗
DOE OSTI2019

Climate change and invasion may synergistically affect native plant reproduction

Global change drivers can interact in synergistic ways, yet the interactive effect of global change drivers, such as climatic warming and species invasions, on plant pollination are poorly represented in experimental studies. We paired manipulative experiments to probe two mechanistic pathways through which plant invasion and warming may alter phenology and reproduction of native plant species. In the first, we tested how experimental warming (+1.7°C) modulated flowering phenology and how this affected flowering overlap between a native plant (Dracophyllum subulatum) and an invasive plant (Calluna vulgaris L.). In the second experiment, we explored how variation in the ratio of native to invasive flowers, and the overall quantity of resources in a floral patch, affected the reproduction of the native species. We hypothesized that the flowering overlap of native and invasive plants would be altered by warming, given that invading plants typically exhibit greater phenological plasticity than native plants. Further, we hypothesized that pollination of native plant flowers would decrease in floral patches dominated by invasive plant flowers, but that this effect would depend on total floral density in the patch. As predicted, the invasive plant had a stronger phenological response to experimental warming than the native plant, resulting in increased flowering overlap between the native the invasive plants. There was a four-fold increase in the number of native flowers co-flowering with high densities of invasive flowers suggesting native plant competition for pollinators with invasive plants under a warmed climate. In the second experiment, we found depressed seed masses of the native species in high density floral patches that were dominated by invasive flowers relative to high density floral patches dominated by native flowers. At low floral densities, seed mass of native plants was unaffected by invasion. Together, these results demonstrate that by increasing their phenological overlap, warming may enhance the magnitude of existing competition for pollination exerted by an invasive plant on a native plant, particularly in plant patches with high floral density. Finally, our results illustrate a novel pathway through which global change drivers can operate synergistically to alter an important ecosystem service: pollination.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Quantitative trait locus (QTL) mapping and transcriptome profiling identify QTLs and candidate genes associated with heat stress response during reproductive development in Camelina sativa

Camelina sativa (L.) Crantz is a low-input oilseed crop that has great potential in providing sustainable feedstock for biofuels and bioproducts. Climate change is threatening production of camelina with rising global temperatures. Elucidating the genetic response to high temperatures is essential for successful breeding of heat-tolerant camelina varieties. Here, we report a combinatorial approach to identifying candidate genes associated with heat stress by quantitative trait locus (QTL) mapping and comparative transcriptome profiling. A population of recombinant inbred lines (RILs) was grown in a controlled growth chamber under the high-temperature regimes for 14 days beginning at the onset of the reproductive stage. Several traits related to seed production were evaluated at maturity. The QTL analysis identified several regions with co-located traits on chromosomes 8, 10, and 12. Two RILs with contrasting phenotypic responses to heat stress were chosen for gene expression profiling via RNA sequencing. Multiple pathways and genes were found to be strongly affected by heat stress, and many genes expressed differently between the two RILs. Several genes identified within the QTL regions were considered strong candidates that may control heat tolerance during reproduction in camelina. These studies provide resources for future studies that may assist in improving the heat tolerance of camelina.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MOV10 inhibits replication of porcine reproductive and respiratory syndrome virus by retaining viral nucleocapsid protein in the cytoplasm of Marc-145 cells

Highlights: • Porcine reproductive and respiratory syndrome (PRRS) affects industrial pig farming. • N protein is the main protein of PRRS virus (PRRSV) in infected cells which is important for PRRSV replication. • Moloney leukemia virus 10 protein (MOV10) is a new host restriction factor of PRRSV. • MOV10 interacts with PRRSV N protein and inhibits PRRSV replication in vitro. • MOV10 inhibits nuclear entry of N protein, thus impairing viral life cycle. Porcine reproductive and respiratory syndrome virus (PRRSV) has been a major threat to global industrial pig farming ever since its emergence in the late 1980s. Identification of sustainable and effective control measures against PRRSV transmission is a pressing problem. The nucleocapsid (N) protein of PRRSV is specifically localized in the cytoplasm and nucleus of virus-infected cells which is important for PRRSV replication. In the current study, a new host restricted factor, Moloney leukemia virus 10-like protein (MOV10), was identified as an inhibitor of PRRSV replication. N protein levels and viral replication were significantly reduced in Marc-145 cells stably overexpressing MOV10 compared with those in wild-type Marc-145 cells. Adsorption experiments revealed that MOV10 did not affect the attachment and internalization of PRRSV. Co-immunoprecipitation and immunofluorescence co-localization analyses showed that MOV10 interacted and co-localized with the PRRSV N protein in the cytoplasm. Notably, MOV10 affected the distribution of N protein in the cytoplasm and nucleus, leading to the retention of N protein in the former. Taken together, these findings demonstrate for the first time that MOV10 inhibits PRRSV replication by restricting the nuclear import of N protein. These observations have great implications for the development of anti-PRRSV drugs and provide new insight into the role of N protein in PRRSV biology.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men

Highlights: • Phthalate metabolite levels in urine and seminal plasma were detected among 687 men. • Measures taken from urine samples poorly predicted same-day seminal plasma levels. • Metabolite levels varied according to sociodemographic and lifestyle factors. • Venous infusion was associated with higher levels of MBP and DEHP metabolites. Certain phthalates are suspected to be endocrine disruptors that are adversely associated with male reproductive health. However, the predictors and correlations of phthalate metabolite concentrations in urine and seminal plasma among reproductive-aged men have not been thoroughly studied.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Persistent organic pollutants as predictors of increased FSH:LH ratio in naturally cycling, reproductive age women

Highlights: • Endocrine disrupting chemicals pose a threat to female fecundity and reproduction. • Examined organochlorines and a marker of ovarian responsivity, FSH:LH ratio. • Increasing concentrations of estrogenic PCBs predict FSH:LH ratio > 2. • PCB congeners related to airborne exposure are associated with FSH:LH ratio > 2. Although several recent studies suggest endocrine disrupting compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p′, DDE), and hexachlorobenzene (HCB), target different organs and systems in the body, their impact on female reproductive function in humans is not well characterized. We seek to determine the relationship between several known endocrine disrupting compounds and a marker of ovarian responsivity, the FSH:LH ratio (higher ratio indicates less ovarian responsivity). For this analysis, 169 naturally cycling women between 21 and 38 years of age completed interviews and had their blood drawn on day 3 of their menstrual cycle for analyses of toxicants, gonadal sex hormones (E{sub 2} and P{sub 4}), and gonadotropins (FSH and LH). PCB congeners were classified into five groups based on their environmental persistence, distribution in human tissue, and toxicological action, reflecting the structure, mechanism, and known biological activity of individual PCB congeners. For every unit (ppb) increase in the level of the estrogenic PCB group, there was a 5-fold greater risk of a FSH:LH ratio ≥ 2, controlling for individual differences in age, percent body fat, cycle day 3 estradiol levels, parity, alcohol use and cigarette smoking in the past year (exp[ß] = 5; p = ≤0.01). PCB congeners identified as estrogenic were analyzed individually, and, of the 19 potentially estrogenic congeners, five were significantly, and positively related to an increased FSH:LH ratio. Four of these congeners are non-persistent, easily volatilize in the environment, and are easily metabolized, and hence, are indicative of very recent or current exposure. p,p′-DDE and HCB were not associated with FSH:LH ratio. We find a clinical indicator of ovarian responsivity, FSH:LH ratio, is associated with a specific group of estrogenic PCBs. These congeners may become airborne when they volatilize from dredged PCB-contaminated soil or from indoor PCB-containing window caulk and sealants in older buildings leading to inhalation exposure. PCB exposure, particularly to non-persistent, estrogenic congeners, may pose an unrecognized threat to female fecundity within the general population.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Systematic evaluation of the population-level effects of alternative treatment strategies on the basic reproduction number

An approach to estimate the influence of the treatment-type controls on the basic reproduction number, R 0 , is proposed and elaborated. The presented approach allows one to estimate the effect of a given treatment strategy or to compare a number of different treatment strategies on the basic reproduction number. All our results are valid for sufficiently small values of the control. However, in many cases it is possible to extend this analysis to larger values of the control as was illustrated by examples.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Characterization of seminal plasma proteomic alterations associated with the IVF and rescue‐ICSI pregnancy in assisted reproduction

Abstract Background Seminal plasma is a promising diagnostic fluid for male infertility. In assisted reproduction, the seminal plasma‐based characteristics of normozoospermic men achieving successful clinical pregnancy through rescue intracytoplasmic sperm injection after in vitro fertilization failure remain unclear. Objective To identify potential seminal plasma proteins to contribute to a new understanding of unexplained male factor infertility. Materials and Methods An approach with isobaric tags for relative and absolute quantification labeling coupled with liquid chromatography matrix‐assisted laser desorption ionization mass spectrometry was applied to investigate differentially expressed proteins in the seminal plasma of a rescue intracytoplasmic sperm injection pregnancy group versus an in vitro fertilization pregnancy group of normozoospermic men. Result(s) The present work revealed seventy‐three differentially expressed seminal plasma proteins between the in vitro fertilization and rescue intracytoplasmic sperm injection groups. Forty‐five proteins were upregulated, and 28 proteins were downregulated in the rescue intracytoplasmic sperm injection group compared with the in vitro fertilization group. Bioinformatics analyses showed that these altered proteins were involved in various functions, including the kallikrein‐related proteolytic cascade, immune response, and heparin binding. Furthermore, the validity of the proteomic results was verified by Western blot analysis of the proteins (lactoferrin [LTF], fibronectin [FN1], creatine kinase B type [CKB], kallikrein‐2 [KLK2], aminopeptidase N [ANPEP], extracellular matrix protein 1 [ECM1], glycodelin [PAEP], alpha‐1‐antitrypsin [SERPINA1], and semenogelin‐1 [SEMG1]) and immunofluorescence. Moreover, 16% of the seminal plasma proteins identified in the present work have not been reported in previous studies. Discussion This panel of altered seminal plasma proteins associated with unexplained male factor infertility might have clinical relevance and may be useful in the diagnosis and prognosis of idiopathic infertility in in vitro fertilization. Conclusions Our work not only provides a new complementary high‐confidence dataset of seminal plasma proteins but also shines new light onto the molecular characteristics of seminal plasma from normozoospermic men with different assisted reproductive outcomes.

Liu, X.↗