Fertility in high yielding dairy cows: to produce or to reproduce Geert Opsomer Department of Reproduction, Obstetrics and Herd Health Faculty of Veterinary Medicine Ghent University, Belgium
1
Aim of the presentation • To give an updated review on the most important points of interaction between the metabolic adaptations and reproductive function in the modern high yielding dairy cow
2
3
Calving interval in modern dairy herds • Overall: – at herd level most economical models illustrate that a short calving interval is beneficial – at individual cow level: it is probably not for all cows economically beneficial to invest in treatments to shorten the calving interval
• Currently, research is going on to find out: – in which situations an extension of the calving interval is justified – how an extension of the calving interval can be realized: nutritionally and genetically
5
6
100 80 60 40 20 0
10000 8000 6000 4000 2000 0 1951
1975
Conception rate
1985
1996
Milk production (kg/yr)
Conception rate (%)
Milk Production and Fertility in Dairy Cows
Milk Production 7 Butler et al., 1999
Melk productie / koe / jaar
Dairy cows in Belgium 1991 - 2007 10000
425
9000
420
8000
415
7000
410
6000
405
5000
400
4000
395
3000
390
2000
385
1000
380
0
375 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07
9
(Fricke, 2012)
10
High yielding dairy cow 6０kg/day = ± 7 kg solids
11
12
Milk production - NEB GLUCOSE
insuline
LIPOLYSIS
LACTOSE
Melk
NEFA
gluconeogenesis
Ketolichamen
VETTEN
Alternatieve energie bron voor de perifere weefsels GLUCOSE sparen
BHB
13
Adaptation towards high milk yield: Glucosesparing state • • • •
Similar for most pregnant/lactating mammals Lower insulin concentration Lower insulin sensitivity Result: – Lower expression GLUT-4 in muscle, fat – More glucose available for insulin-independent organs • Mammary gland • Gravid uterus
14
- Insulin concentration ↓ - Insulin responsiveness ↓ Feed intake Liver Gluconeogenesis Brain GLUT4 Fat
NEFA
GLUT4
GLUCOSE 90%
GLUT1-3
Mammary gland (Bossaert, 2010)
• Downside of energy prioritization: – long and deep NEB is at the expense of body reserves and in some cases of health and production
16
Overconditioned cows • have a lower dry matter intake • larger fat depots to be broken down Hence are at a higher risk to suffer from: -metabolic diseases: ketosis, fatty liver, hypocalcemia -inflammatory/infectious diseases -fertility problems Fat cow syndrome (Morrow, 1975) 17
Fat cow syndrome
Metabolic syndrome
18
IR, Insulin
Dyslipidemia
IGT, IFG
ED, Vessel
Increased CV Risk
Pro Thrombotic
Hypertension
Visceral obesity
Pro Inflammatory 19
Hormones secreted by the Adipocytes Leptin Food intake Energy expenditure Lipolysis lipogenesis Insulin sensitivity
Resistin
+
Contradicting reports, possibly improvement of insulin sensitivity
+
+
Plasma glucose -> Mechanism ? -> gluconeogenesis FFA oxidation
TNF- Food intake Energy expenditure Lipolysis lipogenesis Insulin sensitivity GLUT-4 LPL
Adiponectin
+
+
ASP
+
triglyceride synthesis via DAG GLUT-4 lipolysis via HSL
IL-6 Food intake Energy expenditure Lipolysis lipogenesis
Many others
20
About apples and pears
21
Omentum score 1: omentum is a rather thin peritoneal ‘mebrane’ with clearly visible blood vessels
22
(Van Eetvelde, 2009)
Omentum score 5: The omentum is that fat that there is no longer a ‘net structure’ is visible
23
(Van Eetvelde, 2009)
Correlation body condition score – omental score 6,00
5,00
Omentum score
4,00
r= 0,202 P=0,085
3,00
2,00
1,00
0,00 0,00
1,00
2,00
3,00
4,00
5,00
6,00
24
Body condition score
(Van Eetvelde, 2009)
Nikkah
(Nikkah et al., 2010)
25
Fatty acids in dairy cows during NEB
26
(Hostens et al., in preparation)
Insulin Resistance and Obesity: Effects of Free Fatty Acids on Muscle
27
Hyperlipidemia causes insulin resistance in cows IVGTT 8 hours after infusion of tallow emulsion
(Pires et al., 28 2007)
Hyperlipidemia causes insulin resistance in cows IVITT 8 hours after infusion of tallow emulsion
(Pires et al., 29 2007)
Not all fatty acids and fat depots are the same • Fat depots: – visceral depots are considered more dangerous than subcutaneous depots • direct contact to the liver, higher possibility to produce adipokines, more sensitive for lipolysis, higher concentration of saturated fatty acids
• Nefas: – saturated fatty acids are proven to be more toxic than unsaturated fatty acids 30
Multiple Factors May Drive Progressive Decline of -Cell Function Hyperglycemia (glucose toxicity) Obesity Insulin resistance Protein glycation
-cell
“Lipotoxicity” (elevated FFA, TG)
Adapted from Unger RH, Orci L. Biochim Biophys Acta. 2002;1585:202-212.
Dr.Sarma@works
Insulin (µU/mL)
IVGTT in periparturient dairy cows
-20
INS1 INS2 INS3 -10
0
10
20
30
40
50
60
NEFA: negatively correlated with AUCins and Peakins
70
Time relative to infusion (min) AUCins
Peakins
600
20
500 15 400 300 200
*
*
10
*
*
5
100 0
0
- 14 d
+ 14 d
+ 42 d
- 14 d
+ 14 d
+ 42 d
(Bossaert, 2010)
33 (Opsomer et al., 1999)
(Vanholder, 2005)
34
(Vanholder, 2005)
35
(Vanholder, 2006)
Conclusion • Lactation: depression of insulin secretion • NEFA inversely related to AUCins (P < 0,001) • Intense lipolysis “downward spiral”
Pancreas
– NEFA suppresses insulin secretion – Low insulin increases lipolysis 36
(Bossaert, 2010)
Main consequences of metabolic adaptations • compromised immunity – pro-inflammatory state • lower peripheral levels of glucose, insulin, IGF-1 • higher peripheral levels of Nefa, β-OH butyrate • very high metabolization rate in the liver 37
Liver as central organ
Daily hepatic blood flow for a 40 liter cow:
50.000 liters
39
Fertility dairy cows The Netherlands Year
ICI
NR 56
No insem/preg
Interval p-1st insem
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
393 397 398 400 401 403 405 408 417 413
67 66 67 68 67 68 68 69 68 68
1.79 1.83 1.82 1.80 1.83 1.81 1.81 1.78 1.80 1.78
85 85 86 89 89 91 95 100 103 102 40
Results of studies based on prog analysis
• 448 Normal cyclical patterns (%) • 78 • 7 Delayed cyclicity (%) • 3 Temp cessation of cyclicity • 3 Prolonged luteal phase (%) • 4 Short cycles • 4 Other irregular patterns
• No. of lactations •
• • • • •
Traditional Modern high herds yielding herds
463 51 21,5 4 21,5 0,5 1,5
Fagan and Roche Opsomer et al. 41 1986 1998
42
Delayed cyclicity: consistently low progesterone concentrations for at least 50 days after calving progesterone ng/ml milkfat
120 105 90 75 60 45
AI pregnant
30 15 0 0
7
14
21
28
35
42
49
56
63
70
77
84
91
98
105
112
119
126
133
140
days post partum 43
Risk factor analysis
Delayed cyclicity: • clinical signs of negative energy balance • health problems
(Opsomer et al., 2000) 44
45
(Butler, 1989)
46
Resumption of ovarian activity after calving Brain
LH
FSH Estradiol
OVARY
> 20%!
METABOLISM
Main factors for ovarian resumption after calving • Peripheral levels of insulin and IGF-1: – both have a direct effect on follicular growth and maturation – both facilitate the work of FSH and LH
• Lower insulin levels: – associated with cystic ovaries (Vanholder, 2005)
• Lower IGF-1 levels: – generally associated with lower fertility (Wathes, RVC)
Effects of negative energy balance Metabolic ‘messengers’
GnRH hypothalamus
pituitary gland (hypofysis)
FSH LH Metabolic ‘messengers’ -Glucose -Ketobodies -Nefa's -Urea
ovary
LH surge Ovulation 49
Transvaginal follicular fluid aspiration
50
51
B-hydroxybutyrate (mM)
β-hydroxybutyrate 2,5 2
serum
1,5
follicular fluid
1 0,5 0 -7
0
11
14
20
26
33
40
46
days to partus (Leroy et al., 2004)
52
NEFA
NEFA (mM)
0,6 0,5 0,4 0,3
serum
0,2
follicular fluid
0,1 0 -7
0
11
14
20
26
33
40
46
days to partus 53
(Leroy et al., 2004)
% 35 30 25 20
serum
15 10
follicular fluid
5 0
oleic acid (C18:1)
Stearic Palmitic Linoleic acid acid acid (C18:0) (C16:0) (C18:2) 54
(Leroy , 2005)
In vitro effect of elevated NEFA levels on proliferation of granulosa cells
48 hr
with palmitic, stearic and/or oleic acid
• fatty acids like palmitic and stearic acid have a significant negative effect on granulosa cell growth and proliferation (Vanholder, 2005) 55
Heat expression (Lopez et al.) >39,5 kg/day n Duration (h) # standing
120 -
