A synopsis of a scientific paper discussing factors contributing to twinning in dairy cattle.
Excerpted from an article of the same title by: M.C. Wiltibank, P.M. Fricke, . Sangsritavong, R. Sartori, and O.J. Ginther. Endocrinology-Reproductive Physiology Program and Dept. of Dairy Science. University of Wisconsin-Madison, Madison, WI, USA. Published in J. Dairy Sci 83:2998.
Ovulation rate appears to regulate litter size. Cattle generally ovulate a single ova, producing only one offspring per pregnancy. Attempts to regulate the twinning rate in cattle have focused on; genetic selection (70, 72), hormonal treatments (45), embryo transfer (2, 9, 66, 67), or immunologic suppression of hormones (32, 48, 74). Twinning in dairy cattle seems to have increased recently with serious ramifications (39). Unfortunately, the basic mechanisms regulating ovulation rate in cattle remain unknown.
Selection of a Single Dominant Follicle
Follicular waves are episodes of follicular growth. The final stages of bovine follicular development from 4 mm diameter to preovulatory size are characterized by follicular waves. Either two or three follicular waves occur during a single estrous cycle in cattle. Follicular waves may also occur during anovulatory conditions such as pregnancy (27, 28), postpartum anovulation (62), and prepubertal anovulation (20).
Thus, follicular waves are a normal part of the regulation of the bovine ovary. The hormone most closely linked to follicular waves is follicle stimulating hormone or FSH. Increased circulating concentrations of FSH occur at the onset of each follicular wave (1).
Follicular deviation occurs when there is an abrupt change in the differences in diameter between the two largest follicles in a follicular wave (28, 30). FSH concentrations reach their lowest levels near the time of deviation (28). Before deviation occurs, the future dominant and the future largest subordinate follicles grow at similar rates. Prior to deviation, any follicle of the wave has the ability to become the dominant follicle (25).
Apparently, one follicle reaches the point of functional deviation before the rest of the follicles in the wave. The associated decrease in FSH, or other inhibitory actions of the dominant follicle, prevents the next follicle to reach a diameter associated with functional and morphological deviation, resulting in an atretic follicle. An increase in follicular estradiol production near the time of deviation, may be critical for the decrease in FSH concentrations.
However, the hypothesis that estradiol production by the future dominant follicle is involved in deviation by reducing FSH concentrations is not conclusive. The idea of estradiol involvement is based on temporal relationships only; the required cause and effect studies have not been done.
Why does a specific follicle become dominant in the wave? In 75% of the waves, the first follicle to emerge becomes dominant. Therefore, the dominant follicle often has a slight size advantage which may allow it to reach the point of deviation earlier than the others. The decrease in FSH concentrations or other systemic changes associated with deviation then appear to “slam the door” so that other follicles cannot proceed to a similar critical developmental stage. Follicular deviation is likely a rapid event, since the largest subordinate follicle is only 6 to 8 h behind the development of the dominant follicle until follicular deviation (28, 25, 30, 40,).
The most mature follicle of the wave is about 8 h ahead of the next follicle in the wave and is most likely the future dominant follicle. The future dominant and largest subordinate follicles grow at the same rate but the larger follicle reaches the critical stage of differentiation just before the next smaller follicle. At this point, deviation occurs. At deviation, FSH concentrations are not adequate for the next follicle to continue through the point of deviation. Thus, only one follicle proceeds as the dominant follicle.
What allows the dominant follicle to continue growing after deviation, while the other follicles undergo atresia? Low FSH concentrations after deviation may continue to stimulate the dominant follicle either due to increased FSH receptors or responsiveness. However, there is no difference in number of FSH receptors between the dominant and largest subordinate follicle (8) and there is no increase in FSH receptors near this period (77).
Responsiveness to LH (ovulation due to an LH surge) occurs after follicular deviation. Responsiveness to LH pulses may allow the dominant follicle to continue to grow, while the subordinate follicles cannot grow with the low circulating FSH concentrations. Other changes within the follicle, such as decreased expression of IGF-binding proteins (46), may also be important for continued development of the dominant follicle in a low FSH environment.
Regulation of Twinning and Double Ovulation
In dairy cattle, twin births are generally undesirable due to increased risk of health problems and/or death (6, 18, 49). As early as the 1920’s a number of possible regulators of twinning rates were identified. These included; age of dam (36), season (13), and genetics (43). Numerous other factors have also been associated with twinning, including use of antibiotics or reproductive hormones, ovarian cysts, days open, and peak milk production (35, 39, 49, 51, 59).
This review will focus on two factors; lactation number and milk production, which the authors believe to be critical determinants of twinning in dairy cows. Parity of the dam is clearly associated with twinning rate; the greatest increase occurs between the first and second calving. In studies with high producing dairy cattle, (7, 59), there was an increase from about 1% twinning in heifers to 6 - 7% in second parity pregnancies. A slight increase in twinning rate has been shown after second parity. In almost all studies high twinning rate was associated with increased milk production, either peak or cumulative milk.
Monozygous twinning rate in dairy cattle cannot be established from the available information; however, the great majority of twins in dairy cattle are probably due to multiple ovulations.
The double ovulation rate in dairy cattle has been determined in only a few studies. It seems likely that the physiological effects of milk production have a closer linkage with ovulation rate than with twinning rate, per se.
Potential Mechanism Producing Multiple Ovulations
Increases in ovulation rate may be due to many physiological situations. These increases may be due to differing mechanisms or multiple situations leading to a common underlying mechanism. (Sartori and Wiltbank, unpublished). The authors found that out of 27 multiple ovulations in dairy cows, all except two of the ovulated follicles came from the same follicular wave (92.6%). In contrast, multiple ovulations in sheep (26, 63) are often associated with multiple ovulatory follicular waves.
What hormonal mechanisms might allow two follicles to arise from a follicular wave rather than just one? A number of scenarios may result in a lack of follicular deviation. One is that the future dominant and subordinate follicles are at a similar stage of differentiation such that both reach the point of deviation at approximately the same time. This event requires a disruption in the normal follicular hierarchy that results in about an 8-h interval between each follicle in a follicular wave. This is a fairly speculative concept, and published data is lacking to refute or support a disruption of follicular hierarchy due to milk production.
Another possible mechanism is that FSH concentrations do not diminish sufficiently at the time of deviation to prevent the subordinate follicle from further development. The authors have preliminary data that supports this scenario. Differences in FSH concentrations that could lead to double ovulation are not large and occur only for a short time near the normal time of deviation. The authors propose a physiological model to account for a relationship between high milk production and increased ovulation rate. The central point of this model is that metabolism of the follicular factor causing depressed FSH is elevated in high producing lactating dairy cows. The authors assume estradiol to be this critical factor, although another factor may be more important and could be regulated in a similar manner as described.
High milk production generally results in high dry matter intake (DMI) (31). The high DMI is likely to stimulate high blood flow to the digestive tract; all blood flow from the gut must pass through the liver. Increased liver blood flow would be expected to increase steroid metabolism because blood that passes through the hepatic circulation is essentially cleared of steroid (50). Other hormonal factors might also be metabolized at an increased rate with elevated DMI. Thus, high DMI leads to increased metabolism of follicular factors critical for the final depression in FSH that occurs near follicular deviation.
The concept that acute feeding leads to increases in liver blood flow and steroid metabolism is supported by a substantial data set (50, 57, 71). Blood flow and steroid metabolism may be greatly increased in lactating dairy cows due to a chronic high feed intake as well as acute feeding of a large meal. The bottom portion of Figure 3 compares and contrasts the possible physiology leading to double ovulation compared with single ovulation (upper portion). High feed consumption and high hormone metabolism would result in a transient elevation of circulating FSH and physiological selection of a second dominant follicle. This scenario is consistent with the obvious links between high milk production, increased hormone metabolism, and double ovulation. This working physiological model must be tested experimentally before it can be confirmed, modified, or refuted.
Other possible physiological scenarios may explain double ovulation. The growth hormone/IGF-I system has been found to have numerous reproductive effects (for review see 42). Increased circulating concentrations of IGF-I have been associated with increased ovulation rate (16, 65). Data on whether circulating or follicular IGF-I causes increased ovulation rate in cattle must be considered inconclusive at this time. It is possible that small changes in FSH concentrations near the time of deviation could be involved as described above.
1. Adams, G. P., R. L. Matteri, J. P. Kastelic, J.C.H. Ko, and O.J. Ginther. 1992. Association between surges of FSH and emergence of follicular waves in heifers. J. Reprod. Fertil. 94:177-188.
2. Anderson, G.B., P.T. Cupps, and M. Drost. 1979 Induction of twins in cattle with bilateral and unilateral embryo transfer. J. Anim. Sci. 49:1037-1042.
6. Beerpoot, G.M.M., AA. Dykhuizen, M. Nielen, and Y.H. Schukken. 1992. The economics of naturally occurring twinning in dairy cattle. J. Dairy Sci. 75:1044-1051.
7. Berry, S. L., A. Ahmadi, and M. C. Thurmond. 1994. Periparturient disease on large, dry lot dairies: interrelationships of lactation, dystocia, calf number, calf mortality, and calf sex. J. Diary Sci. 77(Suppl. 1):379. (Abstr.)
8. Bodensteiner, K. J., M.C. Wiltbank, D.R. Bergfelt, and O. J. Ginther. 1996. Alterations in follicular estradiol and gonadotropin receptors during development of bovine antral follicles. Theriogenology.
9. Boland, M.P., and I. Gordon. 1978. Twinning in lactating Friesian cows by non- surgical egg transfer. Vet. Rec. 103:241.
13. Cole, L. J., and A. Rodolfo. 1924. Seasonal distribution of twin births in cattle. Rec. Proc. Am. Soc. Anim. Prod., Annual Mtg. 116-118.
16. Echternkamp, S.E., L.J. Spicer, K. E. Gregory, S.F. Canning, and J.M. Hammond. 1999. Concentrations of IGF-I in blood and ovarian follicular fluid of cattle selected for twins. Biol. Reprod. 43:8-14.
18. Eddy, R. G., O. Davies, and C. David. 1991. An economic assessment of twin births in British diary herds. Vet. Rec. 129:526-529.
20. Evans, A.C.O., G.P. Adams, and N.C. Rawlings. 1994. Follicular and hormonal development in prepubertal heifers from 2 to 36 weeks of age. J. Reprod. 57:393-401.
25. Gibbons, J. R., M. C. Wiltbank, and O. J. Ginther. 1997. Functional interrelationships between follicles greater than 4mm and the follicle-stimulating hormone surge in heifers. Biol. Reprod. 57:1066-1073.
26. Gibbons, J. R., Kot, D.L. Thomas, M.C. Wiltbank, and O.J. Ginther. 1999. Follicular and FSH dynamics in ewes with a history of high and low ovulation rates. Theriogenology 52:1005-1020.
27. Ginther, O.J., L. Knopf, and J.P Kastelic, 1989. Ovarian follicular dynamics in heifers during early pregnancy. Biol. Reprod. 41:247-254.
28. Ginther, O.J., M.C. Wiltbank, P.M. Fricke, J.R. Gibbons, and K. Kot. 1996. Selection of the dominant follicle in cattle. Biol. Reprod. 55:1187-1194.
30. Ginther, O.J., K. Kot, L.J. Kulick, and M.C. Wiltbank. 1997. Emergence and deviation of follicles during the development of follicular waves in cattle. Theriogenology 48:75-87.
31. Harrison, R.O., S.P. Ford, J.W. Young, A.J. Conley, and A.E. Freeman. 1995. Increased milk production versus reproductive and energy status of high producing dairy cows. J. Dairy Sci. 73:2749- 2758.
32. Hillard, M.A., J.F. Wilkins, L.J. Cummins, B.M. Bindon, C.G. Tsonis, J.K. Findlay, and T. O’Shea. 1995. Immunological manipulation of ovulation rate for twinning in cattle. J. Reprod. Fertil. 49:351-364.
35. Johansson, I., B. Lindhe, and F. Pirchner. 1974. Causes of variation in the frequency of monozygous and dizygous twinning in various breeds of cattle. Hereditas 78:201-234.
36. Jones, S.V.H., and J.E. Rouse. 1920. Relation of age of dam to observed fecundity in domesticated animals. I. Multiple births in cattle and sheep. J. Dairy Sci. 3:260-290.
39. Kinsel, M.L., W.E. Marsh, P.L. Ruegg, and W.G. Etherington. 1998. Risk factors for twinning in dairy cows. J. Dairy Sci. 81:989-993.
40. Kulick, L.J., K. Kot, M.C. Wiltbank, and O.J. Ginther. 1999. Follicular and hormonal dynamics during the first follicular wave in heifers. Theriogenology 52:913-921.
42. Lucy, M.C. 2000. Regulation of ovarian follicular growth by somatotropin and IGF’s in cattle. J. Dairy Sci. 83:1635-1647.
43. Lush, R.H. 1925. Inheritance of twinning in Holstein cattle. J. Hered. 16:273-280.
45. McCaughe, W.J., and C.Dow. 1977. Hormonal induction of twinning in cattle. Vet. Rec. 100:29-30.
46. Mihm, M.T.E. Good, J.L. Ireland, P.G. Knight, and J.F. Roche. 1997. Decline in serum follicle-stimulating hormone concentrations alters key intrafollicular growth factors involved in selection of dominant follicle in heifers. Biol. Reprod. 57:1328-1337
48. Morris, D.G., M.G. McDermott, M.G. Diskin, C.A. Morrison, P.J. Swift, and J.M. Sreenan. 1993. Effect of immunization against synthetic peptide sequences of bovine inhibin alpha-subunit on ovulation rate and twin-calving rate in heifers. J. Reprod. Fertil. 97:255-261.
49. Nielen M., Y.H. Schukken, D.T. Scholl, H.J. Wilbrink, and A. Brand. 1989. Twinning in dairy cattle: A study of risk factors and effects. Theriogenology 32:845-862.
50. Parr, R.A., I.F. Davis, M.A. Miles, and T.J. Squires. 1993. Liver blood flow and metabolic clearance rate of progesterone in sheep. Res. Vet. Sci. 55:311-316.
51. Pfau, K.O., J.W. Bartlett, and C.E. Shuart. 1948. A study of multiple births in a Holstein-Friesian herd. J. Dairy Sci. 31:241-254.
57. Ruoff, W.L., and P.J. Dziuk. 1994. Absorption and metabolism of estrogens from the stomach and duodenum of pigs. Domest. Anim. Endrocin. 11:197-208.
59. Ryan, D.P., and M.P. Boland. 1991. Frequency of twin births among Holstein-Fresian cows in a warm dry climate. Theriogenology 36:1-10.
62. Savio, J.D., M.P. Boland, and J.F. Roche. 1990. Development of dominant follicles and length of ovarian cycles in postpartum dairy cows. J. Reprod. Fertil. 88:581-591.
63. Schrick, F.N., R.A. Surface, J.V. Pritchard, R.A. Dailey, E.C. Townsend, and E.K. Innskeep. 1993. Ovarian structures during the estrous cycle and early pregnancy in ewes. Biol. Reprod. 49:1133-1140.
65. Spicer, L.J., J.P. Hanrahan, M.T. Zavy, and W.J. Enright. 1993. Relationship between ovulation rate and concentrations of IGF-I in plasma during the oestrous cycle in various genotypes of sheep. J. Reprod. Fertil. 97:403-409.
66. Sreenan, J.M., D. Beehan, and P. Mulvehill. 1975. Egg transfer in the cow: factors affecting pregnancy and twinning rates following bilateral transfers. J. Reprod. Fertil. 44:77-85.
67. Sreenan, J.M., and M.G. Diskin. 1989. Effect of a unilateral or bilaterial twin embryo distribution on twinning and embryo survival rate in the cow. J. Reprod. Fertil. 87:657-664.
70. Van Tassell, C.P., L.D. Van Vleck, and K.E. Gregory. 1998. Bayesian analysis of twinning and ovulation rates using a multiple-trait threshold model and Gibbs sampling. J. Anim. Sci. 76:2048-2061.
71. Vasconcelos, J.L.M., K.A.Bbungert, S.J. Tsai, F.S. Welchsler, and M.C. Wilkbank. 1998. Acute reduction in serum progesterone concentrations due to feed intake in pregnant lactating dairy cows. J. dairy Sci. 81(Suppl.1):226.
72. Van Vleck, L.D., K.E. Gregory, and S.E. Echternkamp. 1991. Prediction of breeding values for twinning rate and ovulation rate with a multiple trait, repeated reords animal model. J. Anim. Sci. 69:3959-3966.
74. Wise, T.H., and B.D. Schanbacher. 1983. Reproductive effects of immunizing heifers against androstenedione and oestradiol-17 beta. J. Reprod. Fertil. 69:605-612.
77. Xu, Z., H.A. Garverick, G.W. Smith, M.F. Smith, S.A. Hamilton, and R.S. Youngquist. 1995. Expression of FSH and LH receptor MRNA in bovine follicles during the first follicular wave. Biol. Reprod. 53:951-957.