Disrupted secretory activation of the mammary gland after antenatal glucocorticoid treatment in sheep

Abstract

Antenatal glucocorticoids are administered to women at risk of preterm delivery to prevent neonatal respiratory morbidity. The effects of exogenous glucocorticoids on the development of lactation are unknown. This study investigated the effects of a single dose of antenatal glucocorticoids on secretory activation in sheep before and after parturition. Pregnant ewes (NZ36) were randomised to receive either medroxyprogesterone acetate (MPA) at 118 days of pregnancy and betamethasone at 125 days (BETA group), MPA at 118 days and saline at 125 days (MPA group) or saline at 118 and 125 days (SALINE group). The concentration of lactose, progesterone, cortisol and prolactin in maternal plasma was measured during pregnancy. After term parturition, the concentration of lactose in milk and maternal plasma was measured daily for 5 days. Lambs were weighed at birth and at 5 days of age; milk volume was measured on day 5. The concentration of lactose in maternal plasma increased significantly after betamethasone administration, corresponding to a fall in plasma progesterone. No changes in lactose were observed in MPA or SALINE ewes. Transient decreases in cortisol and increases in prolactin were observed in the BETA group, but not in either the MPA or SALINE group. After parturition, BETA ewes experienced reduced milk yield and lamb weight gain, and delayed increases in milk lactose levels compared with MPA and saline controls. This study demonstrated that, in sheep, antenatal glucocorticoid administration disrupted secretory activation, causing precocious mammary secretion before parturition and compromising postpartum milk production and lamb growth.

Effects of Antenatal Corticosteroids on Urinary Markers of the Initiation of Lactation in Pregnant Women

“…15,16,25 The present study found that PdG excretion in urine increased with advancing gestational age. Unlike our findings for plasma progesterone in sheep, 19 the present study did not find a sustained decrease in PdG concentration in urine after administration of betamethasone. This finding is consistent with other research in women.…”

“…19 In contrast, increasing PdG excretion was positively associated with increasing lactose excretion as occurred with increasing gestational age. These findings suggest that advancing gestational age had a greater impact on the relationship between the concentrations of PdG and lactose in urine than the effect of betamethasone treatment in women.…”

“…This contrasts with the profound disruption of secretory activation observed after term delivery in sheep. 19 Mothers' own milk is the optimum form of nutrition for infants; thus antenatal factors that impact on successful establishment of lactation are pivotal in the development of human health and disease. 32 The effects observed in the present study, although only mild and transient, suggest that further research is indicated on the effects of antenatal corticosteroids on lactation.…”

“…17,18 We showed previously that antenatal corticosteroid administration caused a marked precocious initiation of mammary secretion during pregnancy in sheep and that this was associated with alterations in the secretion of lactogenic hormones, principally progesterone. 19 To our knowledge, no study has attempted to characterize the changes in the mammary gland in pregnant women after synthetic corticosteroid treatment, although plasma progesterone concentration is thought to be unchanged. [20][21][22] The aim of the present study was to investigate the effects on mammary secretion during pregnancy in women after antenatal corticosteroid administration.…”

“…Although 24-hour urinary excretion may provide a more accurate assessment of progesterone metabolites compared with random blood tests, future research should include measurements of plasma progesterone concentration in order to determine if progesterone undergoes same changes that were observed in sheep in our previous study. 19 …”