During the past several decades, selection for increased milk yield has had a temporal association with declines in fertility and reproductive efficiency in dairy cows. In the U.S., an average annual decrease of 0.5 percent in conception rate at first service occurred between 1975 and 1997. In the United Kingdom (between 1978 and 1996) and in Spain (between 1991 and 2000) conception rate at first service decreased 1 percent per year.

Because decreased fertility is one of the primary reasons to cull cows and represents a major economic loss to dairy producers ($300 million per year in the U.S.), this association has generated considerable interest and concern in the dairy industry. Although the temporal association indicates a significant problem, it does not imply a direct effect of milk yield on reproduction. An examination of the underlying biology is needed to ascertain the reason(s) for this association.

Genetics, environment (management) and their interaction clearly contribute to these concurrent trends for increased milk yield and decreased fertility. However, despite considerable effort, the specific physiological mechanism(s) responsible for the linkage of these trends remains unknown.

It is apparent management plays a major role and efforts to increase cow comfort and to minimize stress are beneficial, if not crucial, for successful lactation and reproduction performance. The goal of this [article] is to provide a brief overview of genetic and environmental effects on reproductive physiology and to describe how reproductive, metabolic and stress-related hormones interact to affect reproductive performance of the contemporary cow.

Genetic and environmental impact
Selection for milk yield and improvements in management have more than doubled milk yield per cow in the last 40 years. Genetic correlations between milk yield and reproductive measures are not favorable, so on average, selection for increased milk yield alone is expected to decrease fertility of dairy cows. Breeding programs in the U.S. have been weighted heavily in favor of milk yield, and the minimal attention to reproductive traits in the selection process has contributed to the downward trends in reproductive performance.

Fertility problems have likely been aggravated by the emphasis on development of more angular, less well-conditioned cows. Although benefits of placing more emphasis on reproductive and health traits are recognized, heritability of fertility traits does not exceed 3 percent, and most of the variation in cow fertility is due to environmental effects.

Improving fertility through genetic selection is a long-term strategy that requires collection of reliable data and incorporation of these data in a multi-trait selection index. Use of a multi-trait selection index would be expected to decrease the rate of increase in milk yield per cow but improve overall economic response.

Short-term strategies include cross-breeding efforts designed to capture the benefits of hybrid vigor. Given the genetic correlation between milk yield and fertility, failure to select for fertility traits will make it increasingly difficult for producers to achieve sufficient reproductive performance in their herds.

Regardless of the strategy, improvements in management programs must keep pace with the continued improvements in genetic merit for milk yield. Failure to do so will eventually result in situations where management is insufficient and reproductive performance will suffer. For example, if a new mix of superior reproductive genes could be introduced into the cow today, management would still need to be sufficient to enable the cow to recognize conditions were appropriate for conception.

Inadequate reproductive programs and management efforts that result in insufficient nutrition, less-than-optimal health and decreased cow comfort have negative impacts on both lactation and reproductive performance.

Use of U.S. Holstein semen in other management systems has contributed to international trends for reduced reproductive performance. Hoekstra et al. estimated an 8 percent decline in conception to first service in Holstein Friesian compared to Dutch Friesian cows and suggested the decrease in reproductive performance in the Dutch dairy herd was associated with the introduction of U.S. Holstein genes.

Harris and Klover reported a similar effect in New Zealand. However, the positive association between percent Holstein genes and milk yield confounds these results. Thus, the association does not indicate if the reduction in reproductive function is due to an increased prevalence of deleterious genes, a direct effect of milk yield or an interaction of milk yield with the environment (management).

Royal et al. accounted for the percentage of Holstein genes before estimating the effects of milk yield on fertility in U.K. cows. They determined percent Holstein genes in a cow had no significant effect on reproductive function, whether evaluated by traditional (interval to first service, pregnancy rate to first service) or endocrine-based (postpartum interval to commencement of luteal activity, length of the first postpartum luteal phase, occurrence of persistent corpus luteum (CL) during the first cycle) measurements.

However, Royal et al. did find strong correlations between actual milk yield and endocrine characteristics (commencement of luteal activity). Thus, the phenotypic influence of milk yield on fertility was greater than the influence of Holstein genes on fertility.

Pursley et al. and Peeler et al. have reported that despite similar genetic potential for milk yield, pregnancy rates are greater in Holstein heifers than cows. Genetics of the heifer do not change when she becomes a cow, so these results provide a strong implication that either the greater milk yield of the cow or insufficient management of the cow (or both) is (are) responsible for the decrease in reproductive performance.

Although these results demonstrate the strong influence of environment and support the need for management to match phenotypic performance, they do not rule out the possibility of an increased proportion of specific genes deleterious to reproductive performance or the possibility their influence is greater when milk yield is increased.

Regardless, the reduction in reproductive performance that occurs when heifers become cows implies greater efforts are required to manage (reduce) the negative impacts of insufficient nutrition, less-than-optimal health and decreased cow comfort on reproductive performance when metabolic demands for milk yield are increased.

Lucy reported increased milk yield and good reproductive performance do occur in many dairies and suggest insufficient management is playing a major role in reduced reproductive performance. For example, even within well-managed herds, the highest producing cows do not necessarily have the poorest reproductive performance.

Plots of accumulated energy balance during the first 28 days postpartum against days to first service increase in plasma progesterone with healthy herdmates identified as low, medium or high producers or identified as pregnant or nonpregnant by 100 days in milk, typically indicate no discernible pattern.

Some high-producing cows have large energy deficits in early lactation, yet begin cycling soon after calving and conceive at their first insemination after the voluntary wait period. What is different between these cows and apparently healthy herdmates who produce less, have moderate energy deficits, fail to cycle and fail to conceive?

Management approaches
When cows become pregnant, they initiate a process that commits future resources to fetal development and lactation. If the environment is perceived as insufficient, such a commitment would be unwise. Therefore, from an evolutionary perspective the presence of mechanisms to sense unsafe environments would be beneficial.

In fact, there are multiple places in the reproductive process where adverse stimuli can exert a negative effect on reproduction. These stimuli typically arise as a result of stress and affect one or more portions of the hypothalamic-pituitary-adrenal or the hypothalamic-pituitary-ovarian axis. Insufficient nutrition, discomfort and poor health can elicit multiple stimuli that are common indicators of stress and that can impact either axis at several points and affect reproductive performance.

Nutrition
Nutrition and overall management of the cow can impact the circulating concentrations of hormones and metabolites, and these alterations can have positive and negative impacts on reproductive performance. Several excellent reviews describe management strategies designed to optimize metabolic health of the dairy cow during the periparturient period. This period continues to pose significant challenges to dairy producers.

From 1996 to 2001, 25 percent of the cows that left dairy herds in Minnesota left during the first 60 days of lactation. At the onset of lactation an extensive number of physiological adaptations involving multiple tissues occur in a coordinated manner to support the production of large quantities of milk. For example, the transition from pregnant and nonlactating to nonpregnant and lactating can increase nutritional requirements of the high-producing dairy cow by fourfold.

However, this increase in nutritional requirements is not accompanied by an immediate or sufficient increase in feed intake. Feed intake is reduced at the onset of parturition, and the subsequent rate of increase is not as rapid as the increase in milk yield. Therefore, cows experience a period of significant negative energy balance in early lactation and need to mobilize their tissue reserves to supply substrates and energy for milk production and nonmammary tissues needs.

Tissue mobilization is part of the normal postpartum process and occurs in many species in addition to the dairy cow. Increased magnitude and prolonged duration of negative energy and nutrient status during early lactation can prevent cows from reaching their true genetic potential to produce milk and can be detrimental to several physiological functions, including reproductive performance.

The industry-wide trends for concurrent increases in milk yield and decreases in reproductive performance support the perception that increased milk yield increases severity of negative energy and nutrient balance, increases stress and decreases reproductive performance. Under identical conditions and when consuming the same diet, the low-producing control and high-producing contemporary cows at the University of Minnesota had similar energy balance (length and severity) through the first 70 days of lactation.

Although the contemporary cows produced more milk, they also consumed more feed. These results suggest cows strive to reach energy balance and will do so if given the opportunity. Despite the similar energy balance, early postpartum anestrous was more prevalent in contemporary cows. However, cows that produce more milk partition a greater proportion of consumed energy to milk and delay when they begin to replenish tissue previously mobilized.

It should not be surprising that they also delay when they partition sufficient energy towards other functions, including reproduction. Beam and Butler have demonstrated a significant negative association between days to energy balance nadir (its most negative value) and days to first postpartum ovulation. These results indicate recovery from the daily energy balance nadir (initiation of the return to positive energy balance) is associated with return to cyclicity. However, this association only explains about 10 percent of the variation in days to first postpartum ovulation and is not found in all studies. Magnitude of the energy deficit and initial amount of tissue reserve can affect this relationship.

The relative contributions of milk yield, nutrition and management have not been delineated and likely vary among commercial dairies. Some dairies have overall management schemes that enable most high-producing cows to mobilize large quantities of tissue and achieve good reproductive performance.

How much tissue a cow can safely mobilize depends upon several factors including the cow, the quantity of tissue she has available for mobilization, her access to feed and her environment. Severity and duration of negative energy balance during early lactation vary with body condition score (BCS) at calving, parity, milk yield, management and environmental factors.

Change in BCS is a good indicator of change in energy status of the cow. Increased milk yield has been associated with reduced BCS and a greater negative energy balance. However, several studies have demonstrated milk yield is not an absolute indicator of negative energy balance and that variation in energy balance during early lactation is more associated with energy intake.

Staples et al. reported cows that were anestrous during the first 63 days postpartum consumed less feed, produced less milk and lost more body reserves than cows that resumed estrous activity prior to 63 days in milk. Thus, cows that transition through the periparturient period successfully are better prepared to conceive, and efforts that increase feed intake during this interval benefit both milk yield and reproductive success.

Fertility and reproductive performance have been more associated with changes in BCS than with daily milk yield. Days to first postpartum ovulation increased from 30 days when cows lost 0.5 units or less of body condition to 50 days when cows lost more than 1 unit of BCS during the first month of lactation. Negative energy balance and loss of bodyweight and condition have a negative impact on follicular growth and development.

A reduction in energy balance is accompanied by an increase in the number of small (3-5 mm) and medium (6-9 mm) follicles, but a decrease in the number of large (>10 mm) follicles. Pulse frequency of LH is decreased in cows in negative energy balance, and during the early postpartum period follicular dynamics in cows in poor condition are characterized by waves of follicular growth and artresia without ovulation.

In addition, during intervals of negative energy balance, dominant follicles in cows require more time and need to attain a larger size before blood estradiol concentration is sufficient to induce ovulation. Similarly, dominant follicle diameter and circulating estradiol concentration increase after the nadir of postpartum negative energy balance.

It also has been found that even though lactating cows have larger ovulatory follicles, they had similar or lower circulating estradiol concentrations than dry cows or heifers. This indicates either a reduction in estradiol production by the follicle or a greater rate of metabolism of estrogen by lactating cows.

Poor nutrition and bodyweight loss decrease circulating progesterone concentrations and, as mentioned previously, selection for increased milk yield has reduced plasma progesterone concentration. It has been hypothesized that growth and development of follicles during periods of negative energy balance lead to impaired development of the CL and a reduction in progesterone secretion.

Cows that produce more milk have smaller CL at the peak of lactation and CL size has been correlated positively with circulating progesterone concentration. However, circulating progesterone concentration is determined by rates of secretion and clearance. Clearance rates of progesterone increase with feed intake due, in part, to an increase in hepatic metabolism. Therefore, at least two factors (CL size and feed intake) appear to be responsible for the reduction in circulating progesterone in cows that produce more milk.

Energy status is also associated with changes in the secretion and circulating levels of hormones that regulate intermediary metabolism of carbohydrate, fat and protein. In ruminants, severe or acute feed restriction decreases circulating concentrations of insulin, IGF-I and leptin. Similarly, insulin, IGF-I and leptin concentrations decrease in early lactation. Although circulating concentrations of insulin and IGF-I increase steadily during the early postpartum period, leptin concentrations remain reduced in lactating cows.

Selective breeding for high-yielding cows affects the same metabolic hormones. Despite the postpartum increase in circulating ST concentrations, insulin and IGF-I concentrations remain reduced for a longer duration in high genetic merit cows. These changes in endocrine profiles reflect homeorhetic alterations associated with the metabolic drive to partition nutrients toward greater milk yield.

Feeding dairy cows a diet designed to increase circulating insulin concentrations during early lactation did not modify FSH or LH secretion but did reduce the interval from calving to first ovulation and increase conception rates. These results imply that insulin has a direct effect at the ovarian level. Glucose is the major source of energy for the bovine ovary and preovulatory follicular status is associated with increased intrafollicular insulin and glucose concentrations. These results suggest insulin is involved in follicular maturation and the effect of short-term nutrition on ovulation rate may be mediated by a direct ovarian action of insulin and glucose.

Furthermore, insulin concentration follows an estrouslike rhythm, peaking around estrous, suggesting this hormone is most important during the follicular phase. It has been suggested that insulin is also a key regulator of estradiol production.

As cows transition through the postpartum period, they receive signals that result in gradual increases in intake until intake meets their metabolic needs for continued milk synthesis and replenishment of tissue mobilized in early lactation. Reviews have consistently indicated the largest sources of variation in productive efficiency among cows are related to feed intake and their ability to effectively and successfully partition nutrients toward milk.

This variation among cows is due to a combination of genetic and management differences. The relative contributions of genetics and management have not been established, but several factors that regulate feed intake and nutrient partitioning have been identified. These postpartum effects appear to be natural consequences of the physiological mechanisms that enable the cow to achieve greater yields of milk.

Our understanding is improving, but a comprehensive picture of the specific regulatory components and how management impinges on the individual components of these physiological mechanisms has not yet been developed.

Stress and health
Severe and or prolonged intervals of negative energy balance and mobilization of large amounts of body tissue can have negative impacts on reproductive performance. Cows that mobilize large quantities of body tissue in early lactation to support the metabolic demands of milk synthesis and secretion experience significant energy deficits and are frequently characterized as cows that are stressed by their genetic potential to produce milk.

However, because negative energy balance is more associated with feed intake than milk yield, results suggest that factors that limit feed intake have more pronounced effects on fertility than milk yield. Indeed, as mentioned previously, there are multiple examples of apparently healthy cows that produce large quantities of milk, consume large quantities of feed, mobilize large proportions of their body tissue and conceive at their first eligible service.

Thus, negative energy balance is not an indication of increased milk yield, but it is an indicator of situations where energy intake fails to match energy needs. The important question appears to be what factor(s) are responsible for this insufficient intake and the resulting effects on energy balance and fertility.

Stress can be defined as environmental changes that prevent animals from expressing their full genetic potential. In the context of this review, environmental factors that disrupt the signals required for the cow to achieve the increased intake necessary for a successful transition can be considered as stressors. These stressors can be overt or subtle. Subtle stressors are obviously difficult to detect but may be the most important if only because they are not detected, and awareness of the need for corrective measures is lacking.

An example of a relatively subtle stress, at least from a reproductive performance point of view, is the effect of change in herd social hierarchy in early lactation. Cows that experienced an increase in social status produced more milk and had greater fertility than cows that experienced a decrease in social status. Lameness, milk fever, ketosis and mastitis, in addition to the perhaps obvious effects of dystocia and ovarian cysts, have negative impacts on reproductive performance. These stressors can disrupt the precise timing of endocrine signals within the hypothalamus-pituitary-adrenal axis and the hypothalamus-pituitary-ovarian axis required for a normal estrus cycle.

The most common effect of these stressors is a disruption of the normal pulsatile patterns of GnRH released from the hypothalamus. This change disrupts the frequency and amplitude of LH secretion from the pituitary. These changes result in abnormal ovarian function and can delay or even abolish the LH surge. Similar effects occur when plasma concentrations of adrenocorticotropic hormone (ACTH) are increased.

These alterations in GnRH/LH pulse frequency can prevent complete follicular development (anestrous), result in compromised oocytes that can be fertilized but fail to develop or produce a LH surge that does not cause ovulation and lutenization and results in an ovarian cyst. Given the common occurrence of these stressors in dairies, it is apparent reproductive performance could be improved through management to increase nutrient supply and cow comfort and decrease adverse health episodes.

Summary
Reproductive success is the result of multiple relationships among several factors including genetics, nutrition, cow comfort and health. Because postpartum intakes are initially insufficient to meet the metabolic demands of lactation, cows and many other species experience a postpartum interval of insufficient dietary nutrient and energy supply. Negative energy balance is one factor that has adverse effects on reproductive performance.

Considerable variation in the duration of negative energy balance exists among cows and is affected by the environment and the ability of the cow to effectively partition nutrients and energy toward the production of milk.

Thus, as long as the cow is healthy and management is not limiting her lactation or reproductive performance, variation in the onset of reproductive function postpartum should be expected. Some normal, healthy cows might not be able to achieve a 12-month calving interval because their ability to partition nutrients and energy into milk remains a greater priority than reproduction for a greater interval. PD

References omitted but are available upon request.

—From 2006 Intermountain Nutrition Conference Proceedings