Fetal Programming: Prenatal Testosterone Excess Leads to Fetal Growth Retardation and Postnatal Catch-Up Growth in Sheep

Abstract

Alterations in the maternal endocrine, nutritional, and metabolic environment disrupt the developmental trajectory of the fetus, leading to adult diseases. Female offspring of rats, subhuman primates, and sheep treated prenatally with testosterone (T) develop reproductive/metabolic defects during adult life similar to those that occur after intrauterine growth retardation. In the present study we determined whether prenatal T treatment produces growth-retarded offspring. Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16; prenatal T, n = 32). Newborn weight and body dimensions were measured the day after birth, and postnatal weight gain was monitored for 4 months in all females and in a subset of males. Consistent with its action, prenatal T treatment produced females and males with greater anogenital distances relative to controls. Prenatal T treatment reduced body weights and heights of newborns from both sexes and chest circumference of females. Prenatally T-treated females, but not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of prenatally T-treated females were elevated in the first month of life, a period when the prenatally T-treated females were not exhibiting catch-up growth. This is suggestive of reduced IGF availability and potential contribution to growth retardation. These findings support the concept that fetal growth retardation and postnatal catch-up growth, early markers of future adult diseases, can also be programmed by prenatal exposure to excess sex steroids.

Maternal testosterone levels during pregnancy are associated with offspring size at birth

“…For instance, in sheep, testosterone treatment of the mother during early to mid pregnancy reduced birth weight and height in the offspring of either gender (21). This supports the concept that fetal growth retardation, an early marker of adult diseases, can be initiated through prenatal excess exposure to sex steroids.…”

Does having a twin brother make for a bigger brain?

“…This finding also indicates that in children with male co-twin versus a female co-twin intrauterine growth in general is increased. Indeed, in animals it has been reported that fetal growth can be programmed by prenatal exposure to sex steroids (42). On the other hand, as in our sample birth weight only explained 8% of the variance in total brain volume at 9 years of age, the use of birth weight as a proxy for prenatal testosterone exposure on brain volumes seems tenuous.…”

Digit ratios (2D:4D) determined by computer‐assisted analysis are more reliable than those using physical measurements, photocopies, and printed scans

“…In general, the ratio between the second (2D = index finger) and fourth (4D = ring finger) digits in men is lower than that observed in women (Lutchmaya et al, 2004;Manning et al, 1998). Anatomical evidence of prenatal androgen exposure has gained significance in recent times because there is growing evidence in animal models that adult traits and behaviors including, disease susceptibility may be programmed during fetal development (Abbott et al, 2006;Manikkam et al, 2004 Manning and Bundred, 2000;Robinson, 2006). Previous studies in humans have shown low digit ratios (2D:4D) to be associated with a variety of traits including, enhanced visual spatial ability (Burton et al, 2005;van Anders and Hampson, 2005), increased athleticism (Honekopp et al, 2006a), female homosexuality (Brown et al, 2002;Hall and Love, 2003;Kraemer et al, 2006;Williams et al, 2000), decreased susceptibility to coronary artery disease (Fink et al, 2003;Manning and Bundred, 2000), and greater fertility potential in men (Manning et al, 1998) but lower fertility potential in women (Cattrall et al, 2005).…”