Effects of blocking developmental cell death on sexually dimorphic calbindin cell groups in the preoptic area and bed nucleus of the stria terminalis

Experiment 1 compared the number of cells in the CALB-SDN and surrounding regions in adult males, females, and females injected with estradiol benzoate on the day of birth. In experiment 2, cell number in the CALB-SDN and adjacent regions were compared in wild-type and Bax knockout mice of both sexes. In addition, calbindin-ir cells were quantified within the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), a nearby region that is larger in males due to Bax-dependent cell death.Males had more cells in the CALB-SDN as well as in surrounding regions than did females, and estradiol treatment of females at birth masculinized both measures. Bax deletion had no effect on cell number in the CALB-SDN or surrounding regions but increased calbindin-ir cell number in the BNSTp.The sex difference in the CALB-SDN of mice results from an estrogen-dependent difference in cell number with no evidence found for greater spread of cells in females. Blocking Bax-dependent cell death does not prevent sex differences in calbindin-ir cell number in the BNST or CALB-SDN but increases calbindin-ir cell number in the BNSTp of both sexes.The sexually dimorphic nucleus of the preoptic area (SDN-POA) was discovered over 30 years ago in rats and is arguably the best-studied sex difference in the mammalian brain [1,2]. Based on measurements in Nissl-stained sections the nucleus is several times larger in volume in male rats than in females, and similar sex differences have been described in the medial POA of other mammals, including gerbils, guinea pigs, sheep, ferrets, hyenas, monkeys, and humans [3-10].The sex difference in SDN-POA volume in rats depends on estrogenic metabolites of testosterone and is thought to be due to differential cell death during postnatal development. Male rats have more cells in the SDN-POA than do females, beginning by the second postnatal week [11-14], and females have a higher rate of cell death between postnatal days 7 and 10 [12,15,16]. Treati