Source: UNIVERSITY OF MISSOURI submitted to NRP
PREVENTING HEAT-INDUCED MALE INFERTILITY WITH MEDICINAL HERBS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0213989
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Oct 1, 2008
Project End Date
Sep 30, 2010
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF MISSOURI
(N/A)
COLUMBIA,MO 65211
Performing Department
ANIMAL SCIENCES
Non Technical Summary
Producers in the Southern states, such as Missouri, have to deal with heat stressed livestock during the summer. Heat stress decreases the animals production which leads to a loss of income for the producer. National economic losses due to decreased reproduction of livestock resulting from heat stress average approximately $543 million, $40 million, and $51 million annually for dairy, beef, and swine, respectively. Missouri producers alone concede an estimated $17 million, $2 million, and $5 million in dairy, beef, and swine industries, respectively, to reproduction losses. A large proportion of the losses are due to infertility of heat-stressed males. Previous studies from our laboratory have identified epididymal tissue damage and reduced number of offspring from heat-stressed male mice (24h, 35C) compared to non heat-stressed controls. The overall aim of this experiment is to identify practical interventions which reduce the negative effects of heat stress on male fertility. Specifically, we seek: 1) to identify the mechanism through which Artemisia afra maintains nearly normal fertility in heat-stressed males; and 2) to determine if similar effects are elicited by the more readily available Artemisia absinthium. Four groups of ten male mice will be used in the study. Males (n = 5 per heat-stress treatment) will be implanted with abdominal temperature transmitters to record core body temperature. Males will be offered a tea of the test plants as their drinking water for five days before a 24 hour period of moderate heat stress. Remaining males will be hemicastrated to collect testes tissue for measurement of activity of specific genes previously identified as affected by heat stress. Fertility of all males will then be tested in two mating trials, one with two females from days 3-11 following heat stress (this period is to confirm fertility of males independent of the effects of heat stress), a period when no loss in fertility is expected, and subsequently with eight females per male on days 18-28 following heat stress, a period when fertility is expected to be impaired. Feed and water consumption, body temperature, gene expression and number of pregnancies and progeny will be compared among five treatment groups: a non heat-stressed negative control, a non treated heat-stressed positive control, and two groups provided teas of Artemisia afra, or Artemisia absinthium.
Animal Health Component
30%
Research Effort Categories
Basic
30%
Applied
30%
Developmental
40%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3013310102020%
3013410102020%
3013510102020%
3013840102040%
Goals / Objectives
1) National economic losses from heat stress causing decreased reproduction average $543 million, $40 million, and $51 million annually for dairy, beef, and swine, respectively. Missouri producers concede approximately $17 million, $2 million, and $5 million in dairy, beef, and swine production, respectively, due to reproduction losses. 2) We have previously shown that heat-stress induced male infertility is lowly heritable and have identified genes differentially expressed between males susceptible versus resistant to heat stress. 3) We have also shown that pretreatment with Artemisia afra prevents heat-stress induced infertility in mice. Identification of the mechanism of effect of Artemisia, as well as possible alternatives to Artemisia afra, will move the livestock industry closer to a preventative for heat-stress induced infertility. Our hypothesis is that medicinal herb Artemisia afra, traditionally used for alleviating heat stress symptoms in humans, will reduce the negative effects of heat stress on male fertility. The overall aim of this experiment is to identify practical interventions which reduce the negative effects of heat stress on male fertility. The specific objectives of this study are: 1) to identify the mechanism through which Artemisia afra maintains nearly normal fertility in heat-stressed males; and 2) to determine if similar effects are elicited by the more readily available Artemisia absinthium.
Project Methods
Mature male mice will be implanted with Mini-Mitter temperature transmitters (n = 6 per treatment) to record core body temperature. Upon recovery from surgery, mice (n = 10 per treatment) will be placed in environmental chambers at control temperature (21+/-1C) for five days and provided tap water (control) or decoctions of Artemsia afra, or Artemisia absinthium. Males will be exposed to heat stress conditions (35+/-1C) for 24 h and then hemicastrated (d 1) to collect tissue for gene expression analyses. Two periods of mating tests will follow, the first from d 3-11 when no reduction in fertility is anticipated (two females/male) to confirm fertility, and the second from d 18-28 when a reduction in fertility in heat-stressed control males is expected (eight females/male). Pregnant females from the second mating period will be sacrificed at d 17 of gestation to count number of fetuses. Total RNA will be extracted from testis tissue (collected d 1) of males from each treatment, plus from non heat-stressed controls, with trizol according to the recommendations of the manufacturer. RNA samples will be treated with DNAse I (Ambion, TX) to eliminate DNA contamination. Following concentration and purification of the samples, RNA quality will be assessed by electrophoresis and spectrophotometry. Analyses using real-time RT-PCR to confirm and quantify relative gene expression differences will be performed on calnexin, heat shock 90kDa protein 1 beta, t-complex protein 1, FK506-binding protein 6, proteosomal subunit 7, and isocitrate dehydrogenase 1. RNA will be reverse transcribed into cDNA using gene specific primers and the amplification kit from Invitrogen. The PE Biosystems ABI Prism 7700 Detection System (5' nuclease detection assay; TaqMan PCR Core Reagents Kit, PE Biosystems)18 will then be utilized to quantify mRNA expression. To avoid potential non-specific amplifications, internal fluorogenic probes will be used. Standard curves and the fluorescent threshold will be established for every gene. Effects of treatment (no heat stress control, heat stress control, Artemisia afra, or Artemisia absinthium) on feed and water consumption, weight gain, number of females mated and number of fetuses will be analyzed using one-way analysis of variance in PROC GLM of SAS. Effects on body temperature will be will be analyzed using repeated measures analysis of variance in PROC MIXED of SAS. For variable for which treatment effects are significant, post-test contrasts of 1) heat-stress versus control, 2) heat stress control versus Artemisia treated, and 3) Artemisia afra versus Artemisia absinthium will be conducted.

Progress 10/01/08 to 09/30/10

Outputs
OUTPUTS: Studies of the effects of Artemisia afra and Artemisia absinthium on reducing the effects of heat stress induced infertility in mice are ongoing. Effects of heat stress on males for one day and five day periods have been completed. Measurements of metabolic rate and activity have been completed in addition to measuring male fertility. Additional studies examining the effects of treating parent on the sexual development an reproduction of progeny have been conducted. Additional studies of the effects on heat stress induced infertility of boars are ongoing. PARTICIPANTS: Scientists: WR Lamberson (Univ. Missouri) TJ Safranski (Univ. Missouri) KM Cammack (Univ. Wyoming) D. Fisher (univ. Western Cape, South Africa) Students: H Smith, A Desaulniers, C Selby (Univ Missouri) Collaborator: T Irrer, Stoney Creek Essential Oils TARGET AUDIENCES: Target audiences are scientists studying reproduction, heat stress or use of medicinal herbs, and commercial companies growing or marketing medicinal herbs. Farmers facing problems with heat stress induced infertility in pigs and dairy cattle are also interested. PROJECT MODIFICATIONS: This work was initiated in mice. Current projects have been extended to pigs.

Impacts
Additional promising results suggesting partial alleviation of detrimental effects of heat stress on male fertility have been observed. In addition, increased activity of males during 24 hour heat stress was measured. Male mice increase fluid consumption of decoctions of Artemisia compared to water both before and during heat stress. No beneficial or adverse effects of Artemisia on progeny reproductive development or reproduction were observed. No consistent differences in metabolic rates of mice given Artemisia before and during heat stress compared to controls given tap water before and during heat stress were observed. Interestingly, although core body temperatures did not differ between mice given Artemisia versus tap water during heat stress, tail temperatures were lower in mice given Artemisia suggesting a redirection of blood flow and a possible mechanism for maintaining cooler testes to increase reproductive rate following heat stress.

Publications

  • H Smith. 2010. Effects of Artemisia afra and Artemisia absinthium on Fertility of Male Mice Exposed to Heat Stress. MS Thesis, University of Missouri.
  • Lamberson WR, H Smith, KM Cammack, TJ Safranski. 2010. Use of Artemisia sp. to alleviate heat stress induced male infertility. Abstract, Midwest Meeting American Society of Animal Science.


Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: Preliminary data suggests that pretreatment with Artemisia afra or Artemisia absinthium may prevent the effects of heat stress on infertility in male mice. Mice given decoctions of the herbs for five days prior to heat stress had greater fluid consumption, higher activity and higher fertility than non treated controls, although body temperature in the herb treated groups was not lower than controls. Results of the study have been presented at scientific meetings. PARTICIPANTS: Collaborators: Dr. David Fisher, University of Western Cape, South Africa; Dr. Kristi Cammack, University of Wyoming; and Dr. Tim Safranski, University of Missouri, Columbia. Heather Smith completed her MS in animal sciences at the University of Missouri using this project as her thesis research. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Results of this study have been sued to secure additional funding in two areas, first to conduct additional research in mice to attempt to identify mechanisms of action, and second, to extend the research to boars to determine if Artemisia is effective in preventing the effects of heat stress in an economically relevant species.

Publications

  • No publications reported this period