Influence of progesterone supplementation during the first third of pregnancy on fetal and placental growth in overnourished adolescent ewes

Abstract

Overnourishing adolescent ewes throughout pregnancy promotes maternal tissue synthesis at the expense of placental growth, which in turn leads to a major decrease in lamb birth weight. As maternal dietary intakes are inversely related to peripheral progesterone concentrations in these adolescent dams, it was hypothesized that supoptimal progesterone concentrations in overnourished dams may compromise the growth of the differentiating conceptus resulting in fewer uterine caruncles being occupied and, hence, fewer placentomes formed. This hypothesis was tested by supplementing overnourished adolescent dams with exogenous progesterone during early pregnancy and determining the impact on pregnancy outcome at term. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. After transfer of embryos, ewes were offered a moderate or high amount of a complete diet (n = 11 per group). A further high intake group received a progesterone supplement each day from day 5 to day 55 of gestation (term = 145 days) to restore circulating progesterone concentrations to moderate values throughout the first third of pregnancy (n = 11). For ewes establishing pregnancies (n = 7 per group), live weight gain during the first 100 days of gestation was 66 ± 4, 323 ± 17 and 300 ± 7 g per day, body condition score at term was 2.1 ± 0.05, 3.0 ± 0.08 and 3.1 ± 0.07 units and the duration of gestation after spontaneous delivery was 148 ± 1.7, 144 ± 0.8 and 143 ± 0.8 days for the moderate intake, high intake and high intake plus progesterone groups, respectively. At delivery, fetal cotyledon mass (136 ± 12.1 versus 57 ± 8.2 g, P < 0.001) and lamb birth weight (5164 ± 151 versus 2893 ± 381 g, P < 0.001) were higher in moderate intake than in high intake dams. Progesterone supplementation restored circulating concentrations to moderate values during the first third of gestation. Lamb birth weight in the high intake plus progesterone group (4150 ± 389 g) was intermediate between the high intake (P < 0.02) and moderate intake (P < 0.05) groups, but this change in birth weight was not associated with corresponding changes in fetal cotyledon mass (76 ± 10.3 g). Moreover, the number of fetal cotyledons was similar in all three groups. Thus, progesterone did not directly affect the growth of the fetal cotyledon but may have influenced placental vascularity, blood flow or nutrient transfer capacity or alternatively the development of the embryonic inner cell mass.

Investigating the causes of low birth weight in contrasting ovine paradigms

“…In contrast, both paradigms are characterized by low circulating progesterone and placental lactogen concentrations versus high prolactin levels. While in both paradigms the former may partially reflect the reduction in placental mass, particularly during the final third of pregnancy, the changes in these hormones are also detected during the first two thirds of gestation (Regnault et al 1999; Wallace et al 2001, 2003 a ). This implies altered trophoblast function as early as 55 days gestation, possibly via reduced trophoblast cell migration (Regnault et al 1999), and these effects continue until near term (135 days gestation, T.R.H.…”

Competition for nutrients in pregnant adolescents: consequences for maternal, conceptus and offspring endocrine systems

“…The second approach to manipulating the placental growth trajectory of overnourished dams has involved supplementing maternal hormones. Progesterone supplementation of overnourished dams from day 5 to 55 of gestation restored circulating hormone levels to control levels and increased lamb birthweight by 30%, but this change was independent of a corresponding change in placental size at delivery, suggesting a direct effect of progesterone on the embryonic inner cell mass (Wallace et al 2003b). Similarly, oestrogen replacement from day 50 to day 90 of gestation failed to impact feto-placental growth or placental vascularity as assessed in late gestation (Yunusova et al 2011).…”

“…Accordingly, by late gestation and relative to normally growing controls, the growth-restricted fetuses of overnourished dams are hypoglycaemic, mildly hypoxic, have low insulin and IGF-1 concentrations and high lactate levels. Absolute umbilical (fetal) uptakes of glucose, oxygen and amino acids are reduced but are normal when expressed on a fetal weight-specific basis (Wallace et al 2002(Wallace et al , 2003b. Similarly, when the fetal sensitivity to insulin and glucose was examined during fetal hyperinsulinaemic-euglycaemic and hyperglycaemic-euinsulinaemic clamps, normal body weight-specific responses to short-term experimental increases in insulin and/or glucose were observed (Wallace et al 2007).…”

“…This may reflect increased metabolic (hepatic) clearance due to the high dietary intakes or reduced placental steroid capacity, and there is evidence to support both scenarios (Lea et al 2007, Redmer et al 2012. Irrespective of the cause, progesterone and oestradiol-17β levels are reduced relative to controls early in pregnancy and remain attenuated thereafter (Wallace et al 1997a(Wallace et al , 2003b(Wallace et al , 2008a. Together low concentrations of these three lactogenic hormones, as well as reduced growth hormone concentrations (Wallace et al 1997b) are likely to underlie the impaired early lactation robustly observed in overnourished adolescents.…”

Cell Signaling During Mammalian Early Embryo Development

“…In response to gestational over-nutrition, placental development and low progesterone early in pregnancy are associated with low birthweight, and early progesterone supplementation increases birthweight without increasing placental cotyledon number (Wallace et al 2003). It was concluded that early progesterone replacement may increase placental vascularity or directly affect the inner cell mass growth rate.…”