The possible origin of within-litter birth weight variation is thoroughly described in Chapter 1, and will only be summarized here. Placental size is an important determinant of fetal growth and largely fixed at day 35 of pregnancy. Uniformity in placental size among littermates at day 35 of pregnancy, therefore, will be reflected in subsequent fetal growth and litter uniformity [based on Van der Lende et al. (1990)]. Uniformity in placental size is directly related to uniformity in embryo development at elongation and onset of implantation at ~ day 12 of pregnancy, because the more developed embryos start to elongate earlier and occupy a more than equal share of the uterine space, ultimately resulting in a larger placenta (Geisert and Schmitt 2002; Vallet et al. 2009). Indications exist that early embryo uniformity reflects follicle and oocyte uniformity (Pope 1988; Pope et
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al. 1990; Xie et al. 1990a, b). Within-litter piglet weight variation at birth, therefore, is the consequence of very early existence of within-litter variation in early embryo development, which likely reflects variation in follicle and oocyte development.
Within-litter ranking of size of embryos or weight of fetuses, thus, remains more or less the same throughout pregnancy, and a high within-litter variation in early embryo development will result in a high within-litter variation at term. However, several mechanisms may modulate within-litter variation during pregnancy.
Mechanisms that may add within-litter variation during pregnancy
Embryos enter the uterus within ~ 2 - 3 days after fertilization when they are at the ~ 4-cell stage of development (Dziuk 1985). Between day 7 and 12 of pregnancy, the embryos migrate from the oviductal end of the uterine horn and redistribute themselves over the full length of both uterine horns by uterine motility (Pope et al. 1982; Dziuk 1985), although slightly more embryos will stay in the horn of origin than migrating to the other horn (Dziuk 1985). An uneven or disproportional spacing and distribution of embryos through the length of the uterine horns may interfere with the (genetic) growth potential of the
figure 8.1 Mortality of live born piglets during lactation for different birth weight classes (in % of number of live born piglets) for litters with low (< 22%) or high (≥ 22%) birth weight CV (based on live born piglets in birth litter); ab bars with different superscript differ P < 0.10 (corrected for the random effect of birth litter); adapted from Chapter 6.
0 10 20 30 40 50 60 70 80 90 100 <1.0 1.0-1.2 1.2-1.4 1.4-1.6 ≥1.6 M or ta lit y da y 0- w ea ni ng , %
Individual piglet birth weight, kg
Litter birth weight CV < 22% Litter birth weight CV ≥ 22%
a b
embryos, and thereby add additional within-litter variation in development, because a portion of the uterine horn with a disproportional high embryo density may not provide sufficient uterine space to support maximum growth of these embryos at a later stage of pregnancy. Dziuk (1985, 1992), for example, stated that embryo density is highest in the central portion of the uterus (near the cervix) and decreases towards the tips of the uterine horns (Dziuk 1992), and reported that the available uterine space for each embryo at day 25 of pregnancy was highest at the tip of the uterine horn and decreased towards the central portion of the uterus (Dziuk 1985). Possibly related to that, some authors reported that within uterine horns placental weights (from ~ day 30 of pregnancy onwards) and fetal weights (from ~ day 70 of pregnancy onwards) decrease from the ovarian end towards the cervical end of the uterine horn (Perry and Rowell 1969; Wise et al. 1997), whereas others found no evidence for a relation between location in the uterus and fetal weights (Van der Lende et al. 1990). Another factor that may possibly add additional within-litter variation in development could be a difference in uterine quality, such as distribution and density of uterine glands, among specific segments within one uterine horn, possibly related to the previous litter.
Mechanisms that may reduce within-litter variation during pregnancy
The existence of within-litter variation in development is inextricably connected with the reproductive strategy of the sow to overproduce, i.e. to produce a high number of piglets with low investment per piglet (Drake et al. 2008). This allows a high number of piglets to survive when conditions are optimal, thereby providing an extra benefit at minimal cost. As soon as conditions become suboptimal, the existence of within-litter variation in development provides a selective advantage, such that the larger piglets, which received more investment, are not harmed by the presence of the smaller ‘surplus’ piglets, which will die early and thus received little investment (Drake et al. 2008). In sows, therefore, there will always be within-litter variation in all stages of development, from oocytes to piglets born at term to piglets weaned. As soon as conditions become suboptimal, this within-litter variation ensures that selectively the less developed ‘surplus’ littermates are lost almost immediately.
In modern sows ~ 23 - 27 oocytes are released at ovulation (Gerritsen et al. 2008a, b; Foxcroft 2012; Hoving et al. 2012; Chapter 3 and 5), and only ~ 13 - 15 piglets are born at term (Chapter 7), and therefore still ~ 30 - 50% of the potential piglets are lost prenatally. Losses due to fertilization failure or lethal genetic defects that may occur before day 10
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of pregnancy are generally low. Most prenatal losses occur during the peri-implantation period (~ day 12 - 16 of pregnancy) and during the fetal stage [from ~ day 30 of pregnancy onwards; Pope and First (1985); Geisert and Schmitt (2002); Foxcroft (2012)].
During early pregnancy, embryos become dependent on the continuously changing uterine environment. Asynchronous development of embryos and the uterine environment results in growth retardation or embryonic death. These changes in the uterine environment are triggered by the more developed embryos (Geisert and Schmitt 2002; Vallet et al. 2009). Selectively the lesser developed embryos will therefore be lost due to asynchrony with the uterine environment (Geisert and Schmitt 2002; Vallet et al. 2009) or because they do not develop fast enough to occupy sufficient uterine space for implantation. As a consequence, a higher uniformity of pre-implantation embryos likely results in a higher number of embryos surviving to ~ day 12 - 16 of pregnancy and thereby to implantation (until ~ day 25 - 30 of pregnancy) than a low uniformity of pre-implantation embryos. Additionally, high ovulation rates result in a higher number of embryos surviving to implantation (Van der Lende and Schoenmaker 1990; Vonnahme et al. 2002), which was also confirmed by the positive correlation between ovulation rate and the number of implantation sites as observed in this thesis (r = 0.36, P = 0.02; Figure 8.2a; adapted from Chapter 5). Both a higher number of ovulations (Van der Waaij et al. 2010) and a higher number of embryos surviving to implantation [i.e. number of implantation sites; Almeida et al. (2000); Vonnahme et al. (2002); Town et al. (2004)], however, result in smaller average placentas (length or weight), likely because the total available uterine space is divided over more embryos. In superovulated gilts, Van der Waaij et al. (2010) found that within-litter variation in placental weight at ~ day 40 of pregnancy also increased with increasing ovulation rate. Using the data of Chapter 5, negative relations between ovulation rate and mean placental length (r = - 0.37, P = 0.01) and dry weight (r = - 0.37, P = 0.01) and between total number of implantation sites and mean placental length (r = - 0.35, P = 0.02) and dry weight (r = - 0.33, P = 0.03) at day 42 of pregnancy were confirmed, as well as positive relations between ovulation rate and within-litter variation (CV) in placental length (r = 0.48, P < 0.01; Figure 8.2b) and dry weight (r = 0.47, P < 0.01) and between the total number of implantation sites and within-litter variation in placental length (r = 0.47, P < 0.01; Figure 8.2c) and dry weight (r = 0.35, P = 0.02). This likely reflects that a higher number of embryos that survive to implantation is associated with a higher number of relatively lesser developed embryos that survive, and thereby an increased within-litter variation in placental development. It is not clear whether an increased ovulation rate is
figure 8.2 Relations between a) ovulation rate and the number of implantation sites; b) ovulation rate and within-litter CV of placental length (of vital fetuses); and c) total number of implantation sites and within-litter CV of placental length (of vital fetuses) at day 42 of pregnancy; dashed lines indicate the mean ovulation rate (27.0), mean number of implantation sites (22.1) and mean within-litter CV of placental length (26.8%); adapted from Chapter 5.
r = 0.36 P = 0.02 5 10 15 20 25 30 35 15 20 25 30 35 40 Im pl an ta tio n si te s, n Ovulation rate, n CTRL (n = 16) INS-L (n = 15) INS-H (n = 15) 0 5 10 15 20 25 30 35 40 45 50 15 20 25 30 35 40 Pl ac en ta l l en gt h C V, % Ovulation rate, n r = 0.48 P < 0.01 r = 0.47 P < 0.01 0 5 10 15 20 25 30 35 40 45 50 5 10 15 20 25 30 35 Pl ac en ta l l en gt h C V, % Implantation sites, n 15 20 25 30 35 an ta tio n si te s, n CTRL (n = 16) INS-L (n = 15) INS-H (n = 15) a) b) c)
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also associated with a higher number of poorer quality oocytes, and thereby an increased within-litter variation already in early embryos.
In modern sows, the number of ovulations, and thereby the number of embryos surviving to implantation, highly exceeds uterine capacity, and from ~ day 30 - 40 of pregnancy onwards uterine capacity becomes limiting for fetal survival (Vallet 2000; Vonnahme et al. 2002; Van der Waaij et al. 2010) and thereby determines the number of fetuses surviving to term. As a consequence, from ~ day 30 - 40 of pregnancy onwards the number of surviving fetuses is not related to ovulation rate anymore (Vonnahme et al. 2002; Van der Waaij et al. 2010; confirmed by data from Chapter 5 at day 42 of pregnancy: r = 0.14, P = 0.34), but e.g. associated with uterine horn length (Vonnahme et al. 2002). Besides uterine horn length (which determines the initial total uterine surface available for implantation), uterine capacity also involves factors as uterine blood flow and density of uterine glands. A lower uterine capacity probably results in a lower number of fetuses surviving to term. Fetuses with the smallest placentas will probably die first if the number of fetuses exceeds uterine capacity (Vallet 2000; Van der Waaij et al. 2010). Thus, independent of the within-litter variation in placental development at the start of the fetal stage (~ day 30 - 40 of pregnancy), a higher uterine capacity results in a higher number of fetuses surviving till term, and thereby also a higher survival of lesser developed fetuses. The more of these lesser developed fetuses survive, the higher the within-litter variation at term. This is confirmed by Van der Lende et al. (1990), who showed that litters (from ~ day 75 onwards till term) containing outliers with a low body weight, have a higher number of fetuses/piglets compared to litters with a normal distribution of fetal/piglet weights (in which the outliers with a low body weight probably died during earlier stages of pregnancy). A more limited uterine capacity, or a higher number of surviving fetuses, also results in a lower uterine blood flow per fetus, and thereby less nutrients extracted per fetus (Pere and Etienne 2000). This may also increase competition among littermates for blood flow and nutrients during pregnancy, and thereby possibly further increase within-litter variation in development, due to an unequal extraction of nutrients where the more developed fetuses with larger placentas will extract relatively more nutrients than the less developed fetuses.
In summary, within-litter variation at birth is the consequence of within-litter variation in early embryo development, which likely reflects variation in follicle and oocyte development. A higher within-litter variation in early embryo development will result in a higher within-litter variation at term. Furthermore, an uneven distribution of embryos
through the length of the uterine horns may add variation during early pregnancy, whereas increased competition among littermates for limited nutrients may further increase within-litter variation during later stages of pregnancy. On the other hand, selective losses of the lesser-developed peri-implantation embryos (~ day 12 - 16 of pregnancy) or the least developed fetuses (from ~ day 30 of pregnancy onwards) will remove part of the within-litter variation during pregnancy. Peri-implantation losses are directly related to the within-litter variation in early embryo development and ovulation rate, whereas fetal losses are determined by uterine capacity.