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We evaluated relationships between preconception adiposity and human offspring sex and sex ratio. Using data from a prospective preconception cohort nested within a randomized controlled trial based at 4 US clinical sites (2006–2012), we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for male:female sex ratio, and log-identity regression to estimate risk differences (RDs) and 95% CIs for male and female livebirth according to preconception adiposity measures. Inverse-probability weights accounted for potential selection bias. Among 603 women attempting pregnancy, there were meaningful reductions in sex ratio for the highest category of each adiposity measure. The lowest sex ratios were observed for obesity (body mass index of ≥30, calculated as weight (kg)/height (m)2, OR = 0.48, 95% CI: 0.26, 0.88) relative to normal body mass index, and the top tertiles (tertile 3) of serum leptin (OR = 0.50, 95% CI: 0.32, 0.80) and skinfold measurements (OR = 0.50, 95% CI: 0.32, 0.79) relative to the lowest tertiles. Reductions were driven by 11–15 fewer male livebirths per 100 women (for obesity, RD = −15, 95% CI: −23, −6.7; for leptin tertile 3, RD = −11, 95% CI: −20, −3.2; and for skinfolds tertile 3, RD = −11, 95% CI: −19, −3.3). We found that relationships between preconception adiposity measures and reduced sex ratio were driven by a reduction in male births. [ABSTRACT FROM AUTHOR]

Background: Prenatal chlamydia has been linked to preeclampsia (PE), a morbid and deadly hypertensive disorder of pregnancy. However, this association is primarily with term PE a milder phenotype of the syndrome. Less is known about the impact of Neisseria gonorrhoeae on PE phenotypes. We determined if gonorrhea was associated with term or preterm PE and if effect modification by maternal characteristics was evident. Methods: This retrospective analysis included 43,727 singleton and first recorded deliveries from an administrative database. Individuals were enrolled between 2011-2021 at one of three hospitals in Houston, TX. Data on maternal characteristics, sexually transmitted infections, medical history, and preeclampsia defined by gestational age of delivery were obtained. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals adjusting for insurance, race/ethnicity, coinfection with chlamydia, syphilis, or HIV, maternal age, and smoking. Relative excess risk due to interaction (RERI) for ORs was used to identify if maternal pregnancy characteristics (maternal age, obesity, foreign-born, race/ethnicity, chronic health conditions, gravidity, and fetal sex) interacted with gonorrhea. Analyses were stratified by these variables if RERI indicated a possible interaction. Results: Over 95% were screened for N. gonorrhoeae and a total of 188 cases were identified. Prenatal gonorrhea was not significantly associated with preterm PE (OR 2.00, 95% CI 0.85-4.75) or term PE (OR 0.82, 95% CI 0.45-1.51). However, RERI suggested interaction between prenatal gonorrhea and maternal age >24, foreign-born status, and male fetal sex. We found trends towards increase in odds of preterm PE among individuals >24 years of age (OR 3.37, 95% CI 1.23-9.20), foreign-born (OR 4.7, 95% CI 1.49-14.80), and those with a male fetus (OR 3.89, 95% CI 1.5-9.8). This was not observed for term PE. Conclusions: Given the rising rates of N. gonorrhoeae, there is a need to optimize screening and prevention strategies in pregnant individuals. We found that in a population with high screening rates and presumed treatment, certain maternal and pregnancy characteristics may enhance odds for preterm PE. Further research is needed to determine the burden of STIs on hypertensive disorders of pregnancy, including investigations into biological effects during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven.Presentation Of the Hypothesis: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer.Testing the Hypothesis: Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis.Implications Of the Hypothesis: Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis polymorphic membrane proteins (Pmps) may increase genital tract inflammation and play a role in virulence. Antibody levels for PmpA, PmpD, and PmpI, measured in densitometric units, were assessed among a pilot sample of 40 C. trachomatis-infected women with mild-to-moderate clinical PID. Women who expressed antibodies to PmpA were less likely to achieve pregnancy (40.0% versus 85.7%; P = 0.042) and less likely to have a live birth (0.0% versus 80.0%; P = 0.005) compared to women who did not express antibody to PmpA. Women who expressed antibodies to PmpI were more likely to have upper genital tract infection (61.5% versus 20.0%; P = 0.026). However, seropositivity to PmpI and PmpD did not modify the risk of reproductive sequelae or inflammation. Seropositivity to chlamydial PmpA may represent a biomarker of increased risk of sequelae secondary to infection with C. trachomatis. [ABSTRACT FROM AUTHOR]

Host-bacteria and bacteria-bacteria interactions can be facilitated by extracellular vesicles (EVs) secreted by both human and bacterial cells. Human and bacterial EVs (BEVs) propagate and transfer immunogenic cargos that may elicit immune responses in nearby or distant recipient cells/tissues. Hence, direct colonization of tissues by bacterial cells is not required for immunogenic stimulation. This phenomenon is important in the feto-maternal interface, where optimum tolerance between the mother and fetus is required for a successful pregnancy. Though the intrauterine cavity is widely considered sterile, BEVs from diverse sources have been identified in the placenta and amniotic cavity. These BEVs can be internalized by human cells, which may help them evade host immune surveillance. Though it appears logical, whether bacterial cells internalize human EVs or human EV cargo is yet to be determined. However, the presence of BEVs in placental tissues or amniotic cavity is believed to trigger a low-grade immune response that primes the fetal immune system for ex-utero survival, but is insufficient to disrupt the progression of pregnancy or cause immune intolerance required for adverse pregnancy events. Nevertheless, the exchange of bioactive cargos between human and BEVs, and the mechanical underpinnings and health implications of such interactions, especially during pregnancy, are still understudied. Therefore, while focusing on the feto-maternal interface, we discussed how human cells take up BEVs and whether bacterial cells take up human EVs or their cargo, the exchange of cargos between human and BEVs, host cell (feto-maternal) inflammatory responses to BEV immunogenic stimulation, and associations of these interactions with fetal immune priming and adverse reproductive outcomes such as preeclampsia and preterm birth., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2024.)

Study Hypothesis: In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture., Study Finding: We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation., What Is Known Already: Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM., Study Design, Samples/materials, Methods: Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups., Main Results and the Role of Chance: Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence., Limitations, Reasons for Caution: Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM., Wider Implications of the Findings: Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome., Study Funding and Competing Interests: This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of Texas Medical Branch at Galveston and funds to Dr M. Kacerovský from the Ministry of Health Czech Republic (UHHK, 001799906). The authors report no conflict of interest., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)