James J. Ireland
Professor, Animal Science and Physiology
Department of Animal Science, Michigan State University
Education/degree information: BS, 1965-69, Austin Peay State University, Clarksville, TN; PhD, Animal Science, 1971-75, University of Tennessee, Knoxville, TN; Postdoctoral Fellow, Reproductive Sciences Program, 1975-77, University of Michigan, Ann Arbor, MI; Senior NIH Fellow, OBGYN, 1986-87, Yale School of Medicine, New Haven, CT
The mechanisms whereby the inherently high variation in total number of follicles and oocytes in ovaries (ovarian reserve) throughout the reproductive lifespan of individuals, which varies from 10,000 to 350,000 at birth and 1920 to 40,960 in 12-mo-old cattle for example, may negatively impact ovarian function and cause or contribute to the relatively large differences in responsiveness to gonadotropin treatments and fertility amongst individuals are unknown. Consequently, development of new therapeutic approaches to improve responsiveness to gonadotropin therapy and fertility in individuals with a diminished ovarian reserve, which is our long-term research goal, has been hindered.
My laboratory was the first to show that young adult cattle with consistently low (≤15 follicles ≥3 mm in diameter) compared with a high (≥25 follicles) number of follicles growing during follicular waves of an estrous cycle also have a much smaller ovarian reserve (Fig. 1, ~5000 vs ~35,000 eggs/follicles in ovaries [2-4]).
We also showed that an inverse relationship exists between FSH secretion and size of the ovarian reserve in young adult cattle [2-4]. For example, individuals with low follicle numbers during waves (Low), which usually comprise 20 to 25% of a herd, also have a small ovarian reserve, very low circulating concentrations of anti-Müllerian hormone , poor response of the ovary  and granulosal , thecal , and luteal  cells to gonadotropin stimulation, and reduced oocyte quality . These individuals also typically exhibit 20 to 50% higher FSH concentrations during estrous cycle compared with age-matched cattle with high follicle numbers (High) and a much larger ovarian reserve (Fig. 2).
Our current research focuses on the impact and associated mechanisms whereby the chronically high FSH secretion during follicular waves in young adult cattle with a small ovarian reserve may disrupt the gonadotropin signaling cascades thereby impairing ovulatory follicle function, egg quality and fertility.
We have also recently reported that the total dose of FSH used for ovarian stimulation during assisted reproductive technology (ART) is inversely associated with live birth rate in women (Fig. 3) independent of their age, oocyte recovery rate or health . Since a diminished ovarian reserve is the major contributor to infertility in women subjected to ART), our current research uses the bovine model to study the impact and associated mechanisms whereby high FSH doses may be detrimental to ovulatory follicle function, egg quality, embryo quality/survival during ART in cattle with a small ovarian reserve.
I collaborate with Dr. Keith Latham, Dr. George Smith, Dr. Richard Pursley, Dr. Joe Folger, Dr. Fermin Jimenez-Krassel and Janet Ireland in the Animal Science Department at Michigan State University (http://www.ans.msu.edu/) and with Dr. Alex Evans (http://www.ucd.ie/research /success/featuredacademics/professoralexevans/) and colleagues at the University College Dublin Agriculture & Food Science Centre, Ireland (http://www.ucd.ie/agfoodvet/) to conduct the aforementioned studies in cattle. I also collaborate with university scientists, industry representatives, and administrators in NIH and NIFA to advance use of domestic species as dual purpose comparative models to resolve critical biological problems common to both animal agriculture and biomedicine ([12, 13], http://www.adsbm.msu.edu/).
1. Erickson BH. Development and senescence of the postnatal bovine ovary. J Anim Sci 1966; 25: 800-805.
2. Ireland JLH, Scheetz D, Jimenez-Krassel F, Themmen APN, Ward F, Lonergan P, Smith GW, Perez GI, Evans ACO, Ireland JJ. Antral follicle count reliably predicts number of morphologically healthy oocytes and follicles in ovaries of young adult cattle. Biol Reprod 2008; 79: 1219-1225.
3. Burns DS, Jimenez-Krassel F, Ireland JLH, Knight PG, Ireland JJ. Numbers of antral follicles during follicular waves in cattle: evidence for high variation among animals, very high repeatability in individuals, and an inverse association with serum follicle-stimulating hormone concentrations. Biol Reprod 2005; 73: 54-62.
4. Ireland JJ, Smith GW, Scheetz D, Jimenez-Krassel F, Folger JK, Ireland JLH, Mossa F, Lonergan P, Evans ACO. Does size matter in females? An overview of the impact of the high variation in the ovarian reserve on ovarian function and fertility, utility of anti-Mullerian hormone as a diagnostic marker for fertility and causes of variation in the ovarian reserve in cattle. Reprod Fertil Dev 2011; 23: 1-14.
5. Ireland JJ, Ward F, Jimenez-Krassel F, Ireland JLH, Smith GW, Lonergan P, Evans ACO. Follicle numbers are highly repeatable within individual animals but are inversely correlated with FSH concentrations and the proportion of good-quality embryos after ovarian stimulation in cattle. Hum Reprod 2007; 22: 1687-1695.
6. Scheetz D, Folger JK, Smith GW, Ireland JJ. Granulosa cells are refractory to FSH action in individuals with a low antral follicle count. Reprod Fertil Dev 2012; 24: 327-336.
7. Mossa F, Jimenez-Krassel F, Folger JK, Ireland JL, Smith G, Lonergan P, Evans ACO, Ireland JJ. Evidence that high variation in antral follicle count during follicular waves is linked to alterations in ovarian androgen production in cattle. Reproduction 2010; 140: 713-720.
8. Jimenez-Krassel F, Folger J, Ireland JLH, Smith GW, Hou X, Davis JS, Lonergan P, Evans ACO, Ireland JJ. Evidence that high variation in ovarian reserves of healthy young adults has a negative impact on the corpus luteum and endometrium during reproductive cycles of single-ovulating species. Biol Reprod 2009; 80: 1272-1281.
9. Ireland JJ, Zielak-Steciwko AE, Jimenez-Krassel F, Folger J, Bettegowda A, Scheetz D, Walsh S, Mossa F, Knight PG, Smith GW, Lonergan P, Evans ACO. Variation in the ovarian reserve is linked to alterations in intrafollicular estradiol production and ovarian biomarkers of follicular differentiation and oocyte quality in cattle. Biol Reprod 2009; 80 954-964.
10. Baker V, Brown M, Luke B, Smith G, Ireland J. Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 ART cycles. Fert Steril 2015; 104: 1145-1152.
11. SART. Society for Study of Reproduction. National Data Summary https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0. In; 2013.
12. Ireland JJ, Roberts RM, Palmer GH, Bauman DE, Bazer FW. A commentary on domestic animals as dual-purpose models that benefit agricultural and biomedical research. J Anim Sci 2008; 86: 2797-2805.
13. Roberts RM, Smith GW, Bazer FW, Cibelli J, Seidel GE, Jr., Bauman DE, Reynolds LP, Ireland JJ. Farm animal research in crisis. Science 2009; 324: 468-469.