**6. Biological pathways of sex-biased milk production**

Dairy calves are usually separated from their mothers right after or within hours of birth and artificially reared; therefore, the differences observed on milk production of the mother should relate to factors affecting the lactogenesis in pre- or peri-natal period [40]. The pathways through which fetal sex may influence milk production are not yet fully understood. Sex-biased milk production may reflect differential cellular capacity in the mammary gland, programmed via hormonal signals from the fetal-placental unit, or post-natal through sex-biased nursing behavior [87]. Several hypothetical mechanisms have been explored in an attempt to explain the mechanisms that may explain a sex-biased milk production in bovine, albeit with discrepant results.

One possible mechanism may relate to the translocation of fetal hormones to the cow mammary gland via the maternal circulation [1]. The concentrations of sexual hormones differ between male and female fetuses and can potentially enhance or inhibit mammary milk synthesis if they get access to the maternal circulation. In the bovine species, fetal steroid hormones are present from the first trimester [1, 88, 89]. The hormones produced by the bovine fetus can cross the placenta to the cow circulation and calf sex influences hormonal levels in the mother [76, 90–94]. Thereby, variations in the blood levels of the hormones involved in lactogenesis may influence milk, dependent on the sex of the calf born [40]. In humans, higher concentrations of circulating androgens during the second trimester were associated with a lower probability of sustaining breastfeeding to three months post-partum, but the effect of fetal sex on the milk production was not directly analyzed [1, 95].

Also, it is possible that the sex of the first parity calf affects milk production for the duration of the productive life of a cow due to the differences in the level of the hormones that influence mammary development, as it has been reported in mice [96], since dairy cows are first bred before they are fully mature, usually with only 60% of their adult weight.

Xiang and colleagues [97] showed gender variations in the placenta weight in both *Bos taurus* and *Bos indicus* pregnancies; the placenta of the male fetus present heavier total placenta weight, better placenta efficiency heavier fetus weight than female fetus. These differences might explain and favor the fact that male calves are usually heavier than the female's.

Differences in the amount of placental lactogen produced between female and male fetus could differently prime the mammary gland of the cow [1]. It is accepted

**221**

*Calf-Sex Influence in Bovine Milk Production DOI: http://dx.doi.org/10.5772/intechopen.93966*

phase of the lactation [105].

priority during lactation [107].

birthweight of the calf in gestation [110].

producers having a higher rate of female calves [34].

production when birth weight was included in the model.

that prolactin and placental lactogens have roles in mammogenesis and lactogenesis but the mechanisms of action of those hormones act are still in discussion, and the role of the calf gender is still unclear [98, 99]. Albeit the information available for bovine is scarce, in humans, differences were found in the levels of placental lactogen in the umbilical cord blood in female and male pregnancies [100]. It was also been shown that glucose-to-insulin ratios were lower in women bearing a female vs. those bearing a male fetus [101]. Both insulin and glucose are important modulators of milk production. The fetal Insulin-like peptide 3 (INSL3) are raised in maternal circulation during pregnancy in male-pregnant dairy cows and diminished in female-pregnant cows [102]. It was also demonstrated that the level of this hormone directly affects milk production [103, 104]. In cows, Insulin and IGF-I concentrations, important metabolic mediators of the energetic metabolism and body condition, are negatively associated with milk yield during the production

Hienddleder et al. [106] showed that total thyroxine concentrations were higher in male pregnancies, while triiodothyronine concentrations were unaffected by fetal gender. Contrastingly, free thyroxine concentrations were higher in female pregnancies of *Bos indicus* genetics, while in the *Bos taurus*, the values for that hormone tend to be higher in male pregnancies. No gender-associated differences were found regarding the Insulin-like growth factors in this study. The changes in the thyroid hormones' concentrations may contribute to a different pattern in gene expression at the mammary gland, due to their galactopoietic role that sets the mammary gland´ s metabolic

Exploring another route, Chew et al. [108] showed that larger calves are associated with higher milk production, maybe related to higher concentrations of estrogen and placental lactogens during gestation. Indirectly, this could be one of the reasons why, in some cases, male calves are associated with higher milk production, since male calves are usually heavier at birth [109]. However, a negative correlation between birthweight and milk production during gestation was also found, leading to the hypothesis that the competition for nutrient between the fetus in gestation and the milk production for the current one would drive a diminished milk production. Yet, it cannot be ruled out that a high milk production is in itself responsible for a smaller

Women giving birth to daughters show upregulation of epithelial/lactocyte genes, which may be associated with increased milk yield [111]. Also, in dairy cattle a sex-biased in nitrogen and energy metabolism during the transition period was observed [112]. Higher odds exist for a male birth in cows that lose less body condition after calving [113, 114]. The depth of the Negative Energetic Balance (NEB) experienced by these cows may affect the sex-biased production of milk to favor one sex or the other. The usually higher NEB that cows go through in more intensive systems may account for the results obtained under highly intensive conditions compared to the ones obtained under less stressful management. Roche et al. [113] showed that a higher loss of body condition score by the cow was associated with a higher rate of born females. Higher milk producer cows usually lose more body condition score and have a higher rate of female calves' gestation [114]. This might be the reason why it seems that the birth of a female is positive to milk production; however, the relationship between these factors might be the inverse, with higher

Cow's milk production increases with the weight of the calf born [115], and male calves mean weight at birth is higher [82]. This difference in calf-sex birth weight can lead to the idea that the milk production is related to sex, when in fact it only reflects the birth weight [40]. Chew et al. [108] found no calf-sex bias in milk

### *Calf-Sex Influence in Bovine Milk Production DOI: http://dx.doi.org/10.5772/intechopen.93966*

*Animal Reproduction in Veterinary Medicine*

calf-sex biased milk production.

albeit with discrepant results.

60% of their adult weight.

usually heavier than the female's.

of unidentified or unrecorded dystocia [40]. The effect of the different degrees of dystocia in milk production or for how long they persist remain unclear [83–85]. In UK Holstein-Friesian cows, moderate calving difficulties resulted in higher milk production. It is possible that some births not needing help and human supervision may experience real difficulties that go unnoticed and are wrongly registered as an easy calving, when they might have had some difficulties without the farmer's notice. Furthermore, it is likely that cows with highly valuated genetic material may

A reduction in milk production was observed between days in milk 10 and 90 after veterinary-assisted calving compared with non-assisted calving, leading to the conclusion that non-assisted cows presented a flatter lactation curve after peak yield [69]. One of the reasons is a reduced dry matter intake in the months postpartum [86]. In Jerseys the effects of calf gender in mothers milk production were not as pronounced as in Holstein-Friesians [40], which can point to a genetic selection of

Dairy calves are usually separated from their mothers right after or within hours

One possible mechanism may relate to the translocation of fetal hormones to the cow mammary gland via the maternal circulation [1]. The concentrations of sexual hormones differ between male and female fetuses and can potentially enhance or inhibit mammary milk synthesis if they get access to the maternal circulation. In the bovine species, fetal steroid hormones are present from the first trimester [1, 88, 89]. The hormones produced by the bovine fetus can cross the placenta to the cow circulation and calf sex influences hormonal levels in the mother [76, 90–94]. Thereby, variations in the blood levels of the hormones involved in lactogenesis may influence milk, dependent on the sex of the calf born [40]. In humans, higher concentrations of circulating androgens during the second trimester were associated with a lower probability of sustaining breastfeeding to three months post-partum, but the effect

Also, it is possible that the sex of the first parity calf affects milk production for the duration of the productive life of a cow due to the differences in the level of the hormones that influence mammary development, as it has been reported in mice [96], since dairy cows are first bred before they are fully mature, usually with only

Xiang and colleagues [97] showed gender variations in the placenta weight in both *Bos taurus* and *Bos indicus* pregnancies; the placenta of the male fetus present heavier total placenta weight, better placenta efficiency heavier fetus weight than female fetus. These differences might explain and favor the fact that male calves are

Differences in the amount of placental lactogen produced between female and male fetus could differently prime the mammary gland of the cow [1]. It is accepted

of fetal sex on the milk production was not directly analyzed [1, 95].

of birth and artificially reared; therefore, the differences observed on milk production of the mother should relate to factors affecting the lactogenesis in pre- or peri-natal period [40]. The pathways through which fetal sex may influence milk production are not yet fully understood. Sex-biased milk production may reflect differential cellular capacity in the mammary gland, programmed via hormonal signals from the fetal-placental unit, or post-natal through sex-biased nursing behavior [87]. Several hypothetical mechanisms have been explored in an attempt to explain the mechanisms that may explain a sex-biased milk production in bovine,

be offered calving assistance from the farmer more often [67].

**6. Biological pathways of sex-biased milk production**

**220**

that prolactin and placental lactogens have roles in mammogenesis and lactogenesis but the mechanisms of action of those hormones act are still in discussion, and the role of the calf gender is still unclear [98, 99]. Albeit the information available for bovine is scarce, in humans, differences were found in the levels of placental lactogen in the umbilical cord blood in female and male pregnancies [100]. It was also been shown that glucose-to-insulin ratios were lower in women bearing a female vs. those bearing a male fetus [101]. Both insulin and glucose are important modulators of milk production. The fetal Insulin-like peptide 3 (INSL3) are raised in maternal circulation during pregnancy in male-pregnant dairy cows and diminished in female-pregnant cows [102]. It was also demonstrated that the level of this hormone directly affects milk production [103, 104]. In cows, Insulin and IGF-I concentrations, important metabolic mediators of the energetic metabolism and body condition, are negatively associated with milk yield during the production phase of the lactation [105].

Hienddleder et al. [106] showed that total thyroxine concentrations were higher in male pregnancies, while triiodothyronine concentrations were unaffected by fetal gender. Contrastingly, free thyroxine concentrations were higher in female pregnancies of *Bos indicus* genetics, while in the *Bos taurus*, the values for that hormone tend to be higher in male pregnancies. No gender-associated differences were found regarding the Insulin-like growth factors in this study. The changes in the thyroid hormones' concentrations may contribute to a different pattern in gene expression at the mammary gland, due to their galactopoietic role that sets the mammary gland´ s metabolic priority during lactation [107].

Exploring another route, Chew et al. [108] showed that larger calves are associated with higher milk production, maybe related to higher concentrations of estrogen and placental lactogens during gestation. Indirectly, this could be one of the reasons why, in some cases, male calves are associated with higher milk production, since male calves are usually heavier at birth [109]. However, a negative correlation between birthweight and milk production during gestation was also found, leading to the hypothesis that the competition for nutrient between the fetus in gestation and the milk production for the current one would drive a diminished milk production. Yet, it cannot be ruled out that a high milk production is in itself responsible for a smaller birthweight of the calf in gestation [110].

Women giving birth to daughters show upregulation of epithelial/lactocyte genes, which may be associated with increased milk yield [111]. Also, in dairy cattle a sex-biased in nitrogen and energy metabolism during the transition period was observed [112]. Higher odds exist for a male birth in cows that lose less body condition after calving [113, 114]. The depth of the Negative Energetic Balance (NEB) experienced by these cows may affect the sex-biased production of milk to favor one sex or the other. The usually higher NEB that cows go through in more intensive systems may account for the results obtained under highly intensive conditions compared to the ones obtained under less stressful management. Roche et al. [113] showed that a higher loss of body condition score by the cow was associated with a higher rate of born females. Higher milk producer cows usually lose more body condition score and have a higher rate of female calves' gestation [114]. This might be the reason why it seems that the birth of a female is positive to milk production; however, the relationship between these factors might be the inverse, with higher producers having a higher rate of female calves [34].

Cow's milk production increases with the weight of the calf born [115], and male calves mean weight at birth is higher [82]. This difference in calf-sex birth weight can lead to the idea that the milk production is related to sex, when in fact it only reflects the birth weight [40]. Chew et al. [108] found no calf-sex bias in milk production when birth weight was included in the model.

The sex of the calf whose birth initiates lactation can influence the milk production in the subsequent lactation because of the hormonal influences on the mammary gland development or due to the calf sex effects on pregnancy length. Also, fetal sex can influence lactation production during pregnancy because cows become pregnant at peak lactation [109].

In the *Cervus elaphus* species, the red reindeer, dominant females give birth to a higher proportion of males than their subordinates. It is known that these dominant hinds produce higher levels of progesterone in the early days of pregnancy, and male blastocysts secrete interferon-tau earlier than females, so the hypothesis is that maternal recognition of pregnancy in dominant hinds is therefore more likely to be successful if the blastocyst is male [116]. Factors such as this at the time of maternal recognition of pregnancy in cattle could also affect calf sex, but this has not been studied yet.

Holstein heifers in the USA, even after administration of bST (bovine somatotropin) still produced significantly higher milk yield if they calve a female offspring, but sex-biased milk synthesis was not observed in parities two through five [1]. Even though hormones can cause sex-biased milk production, other factors such as birth, weight, lactation length and dystocia probably have a higher impact [40].
