Antenatal Betamethasone (B) and Gender Affect 8‐isoprostane Responses to Unilateral Nephrectomy

Antenatal B administration is a potential “1 st hit” to kidney because it reduces nephron number in offspring. Nephron number declines with age (2 nd hit). It is not clear if antenatal B enhances susceptibility to further loss of nephrons (unilateral nephrectomy, UN), nor if gender modulates responses. We wished to determine if antenatal B affects oxidative stress (OS) responses to UN and if responses differ with gender. 1–1.5 year old male and female sheep exposed to B (n=6) or Vehicle (V) (n=6) at 80–81 days gestation underwent UN. Urine was collected 5 and 15 days after UN. Proximal tubule cells (PTC) were cultured and stimulated with Angiotensin II (ANG II). 8‐isoprostane (8‐PGF, marker of OS) excretion, and production of 8‐PGF in media were measured. Data analyzed by ANOVA or t‐test. 8‐PGF excretion increased in B males (3.53±0.53 at 5 th day to 5.4±1.27ng/kg/h at 15 th day post surgery, p<0.05). No increase occurred in B females (p<0.05, compare to B males), nor in male or female V sheep. ANG II stimulated 8‐PGF in PTC from B males 425.00±15.00 %( p<0.01) but not from B females(p<0.01, compare to PTC from B males), nor from male or female V sheep. Thus, antennal B exposure promotes renal OS responses to UN in male but not female offspring. The increased production of 8‐PGF in PTC from B males but not from B females indicates that cells from males are more susceptible to OS caused by ANG II than those of females. Females appear protected from renal OS induced by a 2 nd hit (UN). Supported by HD‐47584 and HD‐17644