Source: UNIVERSITY OF GEORGIA submitted to NRP
HORMONAL MECHANISMS OF SEX RATIO ADJUSTMENT IN CHICKENS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1002759
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jul 1, 2016
Project End Date
Jun 30, 2021
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF GEORGIA
200 D.W. BROOKS DR
ATHENS,GA 30602-5016
Performing Department
Poultry Science
Non Technical Summary
In the commercial layer industry, approximately 50% of chicks are culled immediately after hatch, because they are male. In the US, approximately 226 million male chicks were culled in 2002 alone. On the surface, this practice appears wasteful, however due to their slow growth rate and inferior meat characteristics when compared to broilers, male chicks from layer breeders are just not economical to maintain. If the poultry industry could manipulate layer hens such that a majority of chicks were female, productivity would dramatically increase, and thriftless killing of male chicks would decline. While many attempts have been made to estimate embryo sex and eliminate male eggs prior to hatch, it would be even more fruitful if hens produced more female-bearing eggs from the start. For decades, researchers have documented significant skews in the production of male versus female offspring in a variety of species. Birds have demonstrated a particular aptitude towards manipulating offspring sex, some species producing up to 77% females in response to environmental cues. Such patterns have mainly engaged the interest of ecologists and, to date, the commercial value of these findings has gone untapped. A full understanding of the mechanisms responsible for the control of offspring sex by hens could allow for the purposeful manipulation of chick sex ratios by breeders. Such a method employed within the layer industry could save millions of industry dollars and millions of animal lives as well. Recent studies in four avian species show that females with high levels of stress hormones skew offspring sex ratios significantly towards females. Such an effect would be extremely useful in an industry context, however there are clear concerns with (1) using a steroid-based hormonal treatment on hens and (2) long-term disruptions that have been documented as a side-effect of chronic treatments with stress hormones. Our objective is to determine the mechanism by which corticosterone is acting on offspring sex ratios with an ultimate goal of developing a non-hormonal treatment by which offspring sex can be purposefully controlled.
Animal Health Component
0%
Research Effort Categories
Basic
80%
Applied
0%
Developmental
20%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30132101020100%
Goals / Objectives
The major goals of this project are:1. To determine the mechanism by which corticosterone influences offspring sex in birds2. To determine whether testosterone is also a mediator of offspring sex ratios in birds3. To target when during the sex determination process sex ratio adjustments are taking place.
Project Methods
in Objective: To determine the roles of maternal stress and corticosterone inoffspring sex ratio adjustment in Leghorn chickensHypothesis 1: Long-term elevation of CORT triggers skews in the offspring sex ratio.EXPERIMENT 1a: Effects of chronic stress on offspring sex ratios: The chronic stressor chosen for this experiment is a repeated restraint stress that takes place three times daily for 2 weeks. White Leghorn hens (Hy-line W36) in this experiment will be randomly distributed into one of two treatment groups (n = 100 per group): (1) the chronic stress group, which will be repeatedly restrained by wrapping tightly in a cloth such that the wings are pinned to the body for 10 minute periods three times per day for 2 weeks, and (2) a control group where hens remain unhandled and undisturbed (except for feeding periods) for the same two week period. Stress treatments for all 100 hens per group will take place 2, 4, and 6h after ovulation so as not to interfere with ovulatory processes of the following follicle. Blood samples will be taken from stressed birds following the completion of each stress challenge and from a separate set of undisturbed hens at the same times during the day for comparison. Blood samples will also be taken from a subset of the stressed and control birds at 4 and 6h prior to ovulation (when birds will not be undergoing a stress response but should exhibit elevated baseline CORT levels indicative of chronic stress). CORT as well as testosterone will be measured in blood samples. Finally, CORT concentrations will be measured in the yolk of each collected egg as well. For the duration of this experiment, all 200 hens will be artificially inseminated biweekly using pooled semen from 10 roosters. Fertilized eggs will be collected from stressed and control birds 7d and 14d following the onset of the stress treatments. Eggs will be incubated for 2d and embryos will be separated and sexed using molecular techniques. Sex ratios and yolk CORT as well as circulating plasma concentrations of CORT and testosterone will be analyzed in relation to the two treatment groups, as well as in relation to the position of the egg in the clutch cycle.EXPERIMENT 1b: Effects of chronic exogenous CORT elevation on offspring sex ratios: White Leghorn hens (Hyline 36) in this experiment will be randomly distributed to one of two treatment groups (n = 100 in each): (1) A CORT implant treatment group, which will receive a 1-inch silastic implant containing crystalline CORT (Sigma-Aldrich Co., St. Louis, MO) or (2) a control group receiving an empty control implant. Females will be artificially inseminated using pooled semen from 10 roosters biweekly for 4 weeks. Oviposition will be monitored daily, laying time recorded, and fertilized eggs will be collected 4, 7, and 13d following implantation and incubated for 2d to allow minimal embryonic development. Embryos will be isolated and sexed using PCR-based molecular techniques. Concentrations of CORT and testosterone will be measured in blood samples taken 4h after ovulation as well as 4 and 6h prior to ovulation in females from both treatment groups on days 3, 6, and 12 (to correspond with ovulation of collected eggs above). CORT concentrations will be measured in the yolk of each collected egg as well. Hypothesis 2: CORT influences sex ratios by decreasing the rate of follicular growth.EXPERIMENT 2: Effects of CORT exposure and maternal stress history on follicular growth as it relates to offspring sex ratio:This experiment will be conducted on yolks collected from 400 eggs (100 per treatment group) during Experiments 1a and 1b, in which birds experienced chronic stress and/or chronic CORT elevation. This is because the majority of follicular growth, characterized by the rapid yolk deposition phase stops 24-48h prior to ovulation. Because all eggs for all experiments will be collected after only 2d of incubation, the yolks should still be relatively intact. Yolks will be frozen upon collection sectioned into a 2mm slice.Follicular growth will be calculated by staining yolk rings according to methods described in Young and Badyaev [2004]. This method provides a measure of follicular growth rate during the period of rapid yolk deposition as well as a total time of follicular growth based on the number of yolk rings.To verify that the 2d period of incubation does not change the yolk ring layering, we will initially compare subsamples of freshly collected yolks under the chronic stress conditions to those of yolks that have undergone initial embryonic development.Growth rates and periods from chronically stressed and CORT treated birds will be compared to those from control birds, and growth rates will also be compared with the sexes of embryos collected from the same eggs.Sexes will be coded as 0 for female and 1 for male, and sexes will be analyzed in relation to follicular growth rate using a logistic regression. This experiment will determine whether chronic stress and CORT implants depress follicular growth, and whether follicular growth relates to offspring sex in this species.Hypothesis 3: CORT acts directly at the time of meiotic segregation to skew offspring sex ratiosEXPERIMENT 3a: Treatment with a long-lasting CORT agonist during meiotic segregation:We plan to utilize the long-lasting CORT agonist, 3,5-dihydroxyphenylglycine (DHPG), injected 6h prior to ovulation to determine whether a longer-lasting physiological CORT elevation "catches" the critical window necessary to induce changes in offspring sex ratios. 120 birds will receive either (1) CORT agonist injection or (2) a control injection 6h prior to ovulation, which corresponds to about 2h before meiotic segregation resumes and completes.Oocytes ovulated 6h following injection will take 24h to pass through the oviduct and will thus be collected 29h after injection, incubated, and embryos will be molecularly sexed to determine offspring sex ratios.From a separate set of females (n = 20 per group) blood samples will be collected 1h and 4h following injections to determine the effects of the CORT agonist on circulating CORT and testosterone concentrations.EXPERIMENT 3b: Amelioration of CORT-induced sex ratios skews by acute exposure to a CORT antagonist: To approach the same question in another way, we will implant birds with either a CORT or control implant (n=60 per group, similar to expt. 1 above) and treat half of those birds with RU-486, a glucocorticoid receptor antagonist, at the time of meiotic segregation. Injections of RU-486 will take place 5h prior to ovulation, which corresponds to 1h prior to the completion of chromosome segregation.Eggs will be collected and sexed as described above, and blood samples will also be collected from a separate set of hens as described above.Hypothesis 4: CORT acts through testosterone or another unidentified mediator to influence processes of sex chromosome segregationEXPERIMENT 4: Treatment with Chronic CORT and Testosterone:During this experiment, we will chronically elevate CORT concentrations using a CORT implant as described above, and in a subset of these implanted birds, we will also add a testosterone implant to prevent the CORT-related depression of testosterone concentrations that would normally occur. Birds will receive one of the following (n = 60 per group): (1) 2 1-inch silastic implants (CORT and T)(crystalline CORT and Testosterone obtained from Sigma-Aldrich Co., St. Louis, MO) (2) 2 blank implants (BL), (3)1 T and 1 BL, or 4) 1 CORT and 1 BL. Eggs will be collected 7d and 14d after introduction of the implants. Eggs will be incubated for 8d and embryos will be molecularly sexed as described above. Blood samples will be collected from a separate set of hens 2d, 7d, 10d, and 14d following introduction of the implants to monitor CORT and testosterone concentrations throughout the experiment.

Progress 07/01/16 to 06/30/21

Outputs
Target Audience:We have three target audiences for this work. The first is the poultry industry in which culling of male chicks is a major welfare issue. The work presented here is the next step towards eliminating the need for this practice. The second target audience is zoo associations where current breeding practices of captive birds are yielding a high proportion of male offspring. Technology developed from our work could help even out sex ratios in conservations programs at zoo facilities. Finally, our final target audience is backyard bird breeders who are hoping to produce birds of a particular sex. This work is also applicable to those studying basic reproductive biology because it sheds light on mechanisms involved in meiotic segregation and how hormones control those mechanisms. Changes/Problems:Changes/Problems: We initially proposed to determine the influences of chronic long-term elevations of corticosterone on offspring sex ratios. We were not able to do this because the long-term treatments with both corticosterone and its antagonist abolished laying in hens. Therefore, we shifted our design to take a more mechanistic approach using short-term elevations of both corticosterone and testosterone to determine what was happening in the germinal disc to influence sex ratios. What opportunities for training and professional development has the project provided?During the course of this work, we have trained one PhD student and three MS students as well as one postdoctoral researcher and 25 undergraduate researchers during the course of this work. How have the results been disseminated to communities of interest?Research results have been disseminated through both publication in peer-reviewed journals and presentation at international scientific meetings. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Overall, we now know that the germinal disc is responsive to both androgens and glucocorticoids because it contains receptors for both. We also know that it is unlikely that changing receptor availability underlies sex ratio adjustment in birds. We instead found that in response to corticosterone and testosterone, expression of gene pathways involved in meiotic segregation are altered. In particular, one shared gene pathway (Nuclear chromosome segregation) is altered by both corticosterone and testosterone treatment, and remains a promising avenue for future study in this area.

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Wrobel, E.R., Molina, E., Khan, N.Y., Akingbemi, B.T., Mendonca, M.T. and Navara, K.J., 2020. Androgen and mineralocorticoid receptors are present on the germinal disc region in laying hens: Potential mediators of sex ratio adjustment in birds?. General and Comparative Endocrinology, 287, p.113353.
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Wrobel, E.R., Bentz, A.B., Lorenz, W.W., Gardner, S.T., Mendon�a, M.T. and Navara, K.J., 2020. Corticosterone and testosterone treatment influence expression of gene pathways linked to meiotic segregation in preovulatory follicles of the domestic hen. Plos one, 15: p.e0232120.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Navara KJ, Wrobel ER. (2019) Frequent double ovipositions in a flock of laying hens. Poultry Science. 98:1903-1910.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Curry JE, Navara KJ. (2019) Natural sex ratio bias in Japanese quail, Coturnix japonica. Society for Integrative and Comparative Biology, Tampa, FL.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Navara, K.J., Wrobel, E.R., Bentz, A.B., Lorenz, W.W., Gardner, S. and Mendonca, M.T., 2020, March. Corticosterone treatment influences expression of gene pathways linked to meiotic segregation in preovulatory follicles of the domestic hen. Society for Integrative and Comparative Biology, Austin, TX.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Navara KJ, Wrobel ER. (2019). Can birds lay more than one egg in a day? Yes they can! Society for Integrative and Comparative Biology, Tampa, FL.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Wrobel ER, Molina E, Khan NY, Akingbemi BT, Lorenz WW, Mendon�a MT, Navara KJ. (2019) Responsiveness of the chicken germinal disc to testosterone and corticosterone. Society for Integrative and Comparative Biology, Tampa, FL.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Khan NY, Wrobel ER, Navara KJ. (2018) Comparing the effects of beeswax versus silastic testosterone implants on elevation of plasma testosterone and reproductive condition in laying hens. Society for Integrative and Comparative Biology, San Francisco, CA.


Progress 10/01/19 to 09/30/20

Outputs
Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? See final report

Publications


    Progress 10/01/18 to 09/30/19

    Outputs
    Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

    Impacts
    What was accomplished under these goals? See final report.

    Publications


      Progress 10/01/17 to 09/30/18

      Outputs
      Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

      Impacts
      What was accomplished under these goals? See final report.

      Publications


        Progress 10/01/16 to 09/30/17

        Outputs
        Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

        Impacts
        What was accomplished under these goals? See final report.

        Publications


          Progress 07/01/16 to 09/30/16

          Outputs
          Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

          Impacts
          What was accomplished under these goals? See final report.

          Publications