Sex ratios at birth vary with environmental harshness but not maternal condition

The sex ratio at birth (SRB) may be patterned by maternal condition and/or environmental stressors. However, despite decades of research, empirical results from across the social and biological sciences are equivocal on this topic. Using longitudinal individual-level data from a US population during the interwar period (1918–1939), inclusive of three distinct eras (Spanish Flu, Roaring ‘20 s, and the Great Depression), we evaluate predictions from two theoretical frameworks used to study patterning in SRB – (1) ‘frail males’ and (2) adaptive sex-biased investment theory (Trivers-Willard). The first approach centers on greater male susceptibility to exogenous stressors and argues that offspring survival should be expected to differ between ‘good’ and ‘bad’ times. The second approach contends that mothers themselves play a direct role in manipulating offspring SRB, and that those in better condition should invest more in sons. In-line with ‘frail male’ predictions, we find that boys are less likely to be born during the environmentally challenging times of the Spanish Flu and Great Depression. However, we find no evidence that maternal condition is associated with sex ratios at birth, a result inconsistent with the Trivers-Willard hypothesis

Sex ratios at birth vary with environmental harshness but not maternal condition

The sex ratio at birth (SRB) may be patterned by maternal condition and/or environmental stressors. However, despite decades of research, empirical results from across the social and biological sciences are equivocal on this topic. Using longitudinal individual-level data from a US population during the interwar period (1918--1939), inclusive of three distinct eras (Spanish Flu, Roaring -˜20-‰s, and the Great Depression), we evaluate predictions from two theoretical frameworks used to study patterning in SRB -- (1) -˜frail males" and (2) adaptive sex-biased investment theory (Trivers-Willard). The first approach centers on greater male susceptibility to exogenous stressors and argues that offspring survival should be expected to differ between -˜good" and -˜bad" times. The second approach contends that mothers themselves play a direct role in manipulating offspring SRB, and that those in better condition should invest more in sons. In-line with -˜frail male" predictions, we find that boys are less likely to be born during the environmentally challenging times of the Spanish Flu and Great Depression. However, we find no evidence that maternal condition is associated with sex ratios at birth, a result inconsistent with the Trivers-Willard hypothesis

Porcine coronary smooth muscle expresses NOX1, NOX2, NOX4, and NOX5 isoforms.

<p>Basal mRNA expression of NOX isoforms 1, 2, 4, and 5 in RCA and CSMCs. NOX4 mRNA expression was significantly higher in both porcine RCA (n = 12–13) and CSMCs (n = 13–15). *P<0.05 vs respective NOX1.</p

Inhibition of NOX prevented bFGF upregulation of KCNN4 activity.

<p>24-hour treatment with bFGF (25 ng/mL) increased TRAM-34 sensitive K⁺ channel activity, which was inhibited by addition of Apo (1.0 mM; n = 10–17). Reduction of internal calcium prevented bFGF induced channel activity. (A) Representative ensemble step currents (−70 mV to 100 mV) before and after addition of the KCNN4 specific channel blocker TRAM-34 (100 nM), (B) TRAM-34 sensitive currents at 100 mV in CSMCs treated with bFGF or bFGF+Apo, and in internal calcium-free (-Ca²⁺_i) conditions. *P<0.05 vs control.</p

Inhibition of NOX prevented bFGF upregulation of KCNN4 mRNA expression.

<p>KCNN4 mRNA expression increased approximately 2.5 fold in both RCA (n = 4–6) and CSMCs (n = 15–17) with bFGF (50 ng/mL and 25 ng/mL, respectively) treatment compared to control. Addition of Apo (1.0 mM) abolished bFGF-induced increases in KCNN4 expression, and alone also significantly decreased basal KCNN4 expression in CSMCs. *P<0.05 vs respective control. #P<0.05 vs respective bFGF.</p

NOX siRNA sequences (5′ to 3′).

<p>NOX siRNA sequences (5′ to 3′).</p

bFGF increased NOX-derived O₂^.−<b>production.</b>

<p>bFGF (25 ng/mL) treatment for 24 hours increased DHE fluorescence (red) in CSMCs compared to control. Addition of the NOX inhibitor Apo (1.0 mM) and superoxide scavenger Tempol (1.0 mM) blocked bFGF induced O₂^.− production. DAPI stained nuclei are shown in blue. Data presented are representative images of three different experiments.</p

Knockdown of NOX5 prevented bFGF upregulation of KCNN4 mRNA expression.

<p>Infection with AdNOX5shRNA significantly reduced NOX5 mRNA expression (B) and prevented KCNN4 mRNA upregulation by bFGF (25 ng/mL) in CSMCs, while the control adenovirus (AdβGal) had no effect (A, n = 4). *P<0.05 vs control.</p

Knockdown of neither NOX2 nor NOX4 prevented bFGF upregulation of KCNN4 mRNA expression.

<p>Nucleofection with siNOX2 significantly reduced NOX2 expression but did not prevent upregulation of KCNN4 mRNA expression by bFGF (25 ng/mL) in CSMCs (A, n = 5–9). Similarly, nucleofection with siNOX4 significantly reduced NOX4 expression but did not prevent upregulation of KCNN4 mRNA expression by bFGF (25 ng/mL) in CSMCs (B, n = 5–9). *P<0.05 vs control.</p

Inhibition of NOX prevented bFGF upregulation of KCNN4 protein expression.

<p>Treatment of RCA sections with bFGF (50 ng/mL) caused a significant increase in medial KCNN4 protein expression, while addition of Apo (1.0 mM) inhibited the response to bFGF; (A) representative images and (C) average relative percent positive KCNN4 staining (n = 3). (B) Demonstration of selectivity of anti-KCNN4 staining by antigen pre-absorption and distribution of nitrotyrosine and SM-actin. Positive staining is brown in all images. *P<0.05 vs control.</p