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1. Adventitial Fibrosis and Fibroblast Mechanosensitivity Are Shaped by Sex and Hormonal Status in Pulmonary Arterial Hypertension

   https://doi.org/10.3390/cells15040354  

   Lin, Yufan; Wang, Ariel; Valdez-Jasso, Daniela (February 2026, Cells)

   Pulmonary arterial hypertension (PAH) is marked by vascular remodeling, yet the role of adventitial fibrosis—and its modulation by sex and hormonal status—remains unclear. We examined stage-specific adventitial remodeling and pulmonary artery adventitial fibroblast (PAAF) mechanosensitivity in male, ovary-intact female, and ovariectomized (OVX) female Sprague–Dawley rats with SuHx-induced PAH. Hemodynamics, pulmonary artery histology, and adventitia-specific transcriptional profiling were integrated with in vitro assays of PAAFs exposed to defined substrate stiffness and stretch. All groups developed comparable increases in mean pulmonary arterial pressure, but vascular resistance shift and adventitial fibrosis diverged by sex: intact females showed attenuated increase in pulmonary vascular resistance and transient collagen accumulation, whereas OVX females mirrored the sustained, male-like progression. Extracellular matrix (ECM) gene activation occurred without smooth muscle actin induction, suggesting noncanonical fibrotic pathways. In vitro, intact female PAAFs required higher substrate stiffness to induce profibrotic gene expression, indicating a hormone-modulated stiffness threshold. OVX PAAFs showed persistent transcriptional reprogramming, while stretch-induced ECM upregulation occurred predominantly in male-derived PAAFs. These findings demonstrate that adventitial fibrosis in PAH is shaped by both hormonal and chromosomal sex, independent of hemodynamic severity, and highlight fibroblast mechanosensitivity as a potential target for stage- and sex-specific interventions. 

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2. Effects of reproductive status on behavioral and neural responses to isolated pup stimuli in female California mice

   https://doi.org/10.1016/j.bbr.2023.114727  

   Wilson, Kerianne M.; Arquilla, April M.; Hussein, Manal; Rosales-Torres, Kelsey M.; Chan, May G.; Saltzman, Wendy (October 2023, Behavioural Brain Research)

   The transition to motherhood in mammals is marked by changes in females’ perception of and responsiveness to sensory stimuli from infants. Our understanding of maternally induced sensory plasticity relies most heavily on studies in uniparental, promiscuous house mice and rats, which may not be representative of rodent species with different life histories. We exposed biparental, monogamous California mouse (Peromyscus californicus) mothers and ovariectomized virgin females to one of four acoustic and olfactory stimulus combinations (Control: clean cotton and white noise; Call: clean cotton and pup vocalizations; Odor: pup-scented cotton and white noise; Call + Odor: pup-scented cotton and pup vocalizations) and quantified females’ behavior and Fos expression in select brain regions. Behavior did not differ between mothers and ovariectomized virgins. Among mothers, however, those exposed to the Control condition took the longest to sniff the odor stimulus, and mothers exposed to the Odor condition were quicker to sniff the odor ball compared to those in the Call condition. Behavior did not differ among ovariectomized virgins exposed to the different conditions. Fos expression differed across conditions only in the anterior hypothalamic nucleus (AHN), which responds to aversive stimuli: among mothers, the Control condition elicited the highest AHN Fos and Call + Odor elicited the lowest. Among ovariectomized virgin fe- males, Call elicited the lowest Fos in the AHN. Thus, reproductive status in California mice alters females’ behavioral responses to stimuli from pups, especially odors, and results in the inhibition of defense circuitry in response to pup stimuli. 

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3. Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension

   https://doi.org/10.1152/ajpheart.00046.2021  

   Kwan, Ethan D.; Vélez-Rendón, Daniela; Zhang, Xiaoyan; Mu, Hao; Patel, Megh; Pursell, Erica; Stowe, Jennifer; Valdez-Jasso, Daniela (October 2021, American Journal of Physiology-Heart and Circulatory Physiology)

   Although pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we discriminated the contributions of RV geometric remodeling and alterations of myocardial material properties to changes in systolic and diastolic chamber function. Significant and rapid RV hypertrophic wall thickening was sufficient to stabilize ejection fraction in response to increased pulmonary arterial pressure by week 4 without significant changes in systolic myofilament activation. After week 4, RV end-diastolic pressure increased significantly with no corresponding changes in end-diastolic volume. Significant RV diastolic chamber stiffening by week 5 was not explained by RV hypertrophy. Instead, model analysis showed that the increases in RV end-diastolic chamber stiffness were entirely attributable to increased resting myocardial material stiffness that was not associated with significant myocardial fibrosis or changes in myocardial collagen content or type. These findings suggest that whereas systolic volume in this model of RV pressure overload is stabilized by early RV hypertrophy, diastolic dilation is prevented by subsequent resting myocardial stiffening. NEW & NOTEWORTHY Using a novel combination of hemodynamic and morphological measurements over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we found that compensated systolic function was almost entirely explained by RV hypertrophy, but subsequently altered RV end-diastolic mechanics were primarily explained by passive myocardial stiffening that was not associated with significant collagen extracellular matrix accumulation. 

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4. Playback of broadband vocalizations of female mice suppresses male ultrasonic calls

   https://doi.org/10.1371/journal.pone.0273742  

   Hood, Kayleigh E.; Long, Eden; Navarro, Eric; Hurley, Laura M. (January 2023, PLOS ONE)

   Coleman, Melissa J. (Ed.)

   Although male vocalizations during opposite- sex interaction have been heavily studied as sexually selected signals, the understanding of the roles of female vocal signals produced in this context is more limited. During intersexual interactions between mice, males produce a majority of ultrasonic vocalizations (USVs), while females produce a majority of human-audible squeaks, also called broadband vocalizations (BBVs). BBVs may be produced in conjunction with defensive aggression, making it difficult to assess whether males respond to BBVs themselves. To assess the direct effect of BBVs on male behavior, we used a split-cage paradigm in which high rates of male USVs were elicited by female presence on the other side of a barrier, but which precluded extensive male-female contact and the spontaneous production of BBVs. In this paradigm, playback of female BBVs decreased USV production, which recovered after the playback period. Trials in which female vocalizations were prevented by the use of female bedding alone or of anesthetized females as stimuli also showed a decrease in response to BBV playback. No non-vocal behaviors declined during playback, although digging behavior increased. Similar to BBVs, WNs also robustly suppressed USV production, albeit to a significantly larger extent. USVs suppression had two distinct temporal components. When grouped in 5-second bins, USVs interleaved with bursts of stimulus BBVs. USV suppression also adapted to BBV playback on the order of minutes. Adaptation occurred more rapidly in males that were housed individually as opposed to socially for a week prior to testing, suggesting that the adaptation trajectory is sensitive to social experience. These findings suggest the possibility that vocal interaction between male and female mice, with males suppressing USVs in response to BBVs, may influence the dynamics of communicative behavior. 

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5. Female choice and sexual coercion in wild orangutans (Pongo pygmaeus wurmbii)

   Scott, AM; Susanto, TW; Knott, CD (January 2020, 6th Annual Meeting of the Northeastern Evolutionary Primatologists)

   null (Ed.)

   Due to extreme incongruence in parental investment, the potential for sexual conflict in orangutan reproductive strategies is high. Female orangutans prefer flanged males, but with intense male-male competition and sexual coercion, it is unclear how females are able to exert choice. We hypothesized that female orangutans use initiation and maintenance of associations with preferred males as a mechanism of female choice. We used encounter rates and behavioral measures of proximity maintenance to distinguish between the role of female choice and male coercion in male-female associations in Gunung Palung National Park, West Kalimantan, Indonesia. From May 2018-April 2019, we collected data on initiation, termination, and proximity maintenance during associations between males and cycling females (females without dependent offspring or with offspring over 6 years old). Encounters between cycling females and flanged males were more likely to be female-initiated (83.3%), while encounters with unflanged males were more likely to be male-initiated (80%) (N=16, p=0.035, Fisher’s exact test). Additionally, the Brown Index indicates significantly more female proximity maintenance when cycling females associated with flanged males than unflanged males (N=33, W = 198.5, p= 0.012). However, using long-term data on male-female associations, we found that dyads of flanged males and females were less likely to encounter other males compared to dyads of unflanged males and females (N=542, χ2= 3.3051, df=1, p=0.035). This indicates that flanged males may also use associations to mate guard females. These data indicate that there are behavioral manifestations of both female choice and male coercion in orangutan associations. Funders: NSF (DGE-1247312, BCS-1638823, BCS-0936199), Boston University, Leakey Foundation, Disney Conservation Fund, and US Fish and Wildlife Service (F18AP00898) 

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