In many species, females mate with multiple partners, meaning that sexual selection on male traits operates across a spectrum that encompasses the competition for mates (that is, before mating) and fertilizations (after mating). Despite being inextricably linked, pre- and postcopulatory sexual selection are typically studied independently, and we know almost nothing about how sexual selection operates across this divide. Here we bridge this knowledge gap using the livebearing fish Poecilia reticulata. We show that both selective episodes, as well as their covariance, explain a significant component of variance in male reproductive fitness. Moreover, linear and nonlinear selection simultaneously act on pre- and postcopulatory traits, and interact to generate multiple phenotypes with similar fitness.

Background The recent emergence of COVID-19 poses a global health emergency. One of the most frequently reported data is sex-related severity and mortality: according to the last available analysis on 239,709 patients in Italy, lethality is 17.7% in men and 10.8% in women, with 59% of total deaths being men. Interestingly, the infection rate is lower in males than in females, with 45.8% and 54.2% of positive cases, respectively, suggesting that gender-related factor may worsen disease evolution. A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. Purpose In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. Results Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry. Conclusions Both mechanisms consistently point to the role of sex hormones and sex chromosomes in the differential severity and lethality of COVID-19 in men and women.

Epidemiological studies reported that vitamin D deficiency represents an increasingly widespread phenomenon in various populations. Vitamin D deficiency is considered a clinical syndrome determined by low circulating levels of 25hydroxyvitamin D (25(OH)D), which is the biologically-inactive intermediate and represents the predominant circulating form. Different mechanisms have been hypothesized to explain the association between hypovitaminosis D and obesity, including lower dietary intake of vitamin D, lesser skin exposure to sunlight, due to less outdoor physical activity, decreased intestinal absorption, impaired hydroxylation in adipose tissue and 25(OH)D accumulation in fat. However, several studies speculated that vitamin D deficiency itself could cause obesity or prevent weight loss. The fat-solubility of vitamin D leads to the hypothesis that a sequestration process occurs in body fat depots, resulting in a lower bioavailability in the obese state. After investigating the clinical aspects of vitamin D deficiency and the proposed mechanisms for low 25 (OH)D in obesity, in this manuscript we discuss the possible role of vitamin D replacement treatment, with different formulations, to restore normal levels in individuals affected by obesity, and evaluate potential positive effects on obesity itself and its metabolic consequences. Food-based prevention strategies for enhancement of vitamin D status and, therefore, lowering skeletal and extra-skeletal diseases risk have been widely proposed in the past decades; however pharmacological supplementation, namely cholecalciferol and calcifediol, is required in the treatment of vitamin D insufficiency and its comorbidities. In individuals affected by obesity, high doses of vitamin D are required to normalize serum vitamin D levels, but the different liposolubility of different supplements should be taken into account. Although the results are inconsistent, some studies reported that vitamin D supplementation may have some beneficial effects in people with obesity.

Background Considerable attention has been paid to perfluoroalkyl compounds (PFCs) because of their worldwide presence in humans, wildlife, and environment. A wide variety of toxicological effects is well supported in animals, including testicular toxicity and male infertility. For these reasons, the understanding of epidemiological associations and of the molecular mechanisms involved in the endocrine-disrupting properties of PFCs on human reproductive health is a major concern. Objective To investigate the relationship between PFC exposure and male reproductive health. Design This study was performed within a screening protocol to evaluate male reproductive health in high schools. Patients This is a cross-sectional study on 212 exposed males from the Veneto region, one of the four areas worldwide heavily polluted with PFCs, and 171 nonexposed controls. Main Outcome Measures Anthropometrics, seminal parameters, and sex hormones were measured in young males from exposed areas compared with age-matched controls. We also performed biochemical studies in established experimental models. Results We found that increased levels of PFCs in plasma and seminal fluid positively correlate with circulating testosterone (T) and with a reduction of semen quality, testicular volume, penile length, and anogenital distance. Experimental evidence points toward an antagonistic action of perfluorooctanoic acid on the binding of T to androgen receptor (AR) in a gene reporter assay, a competition assay on an AR-coated surface plasmon resonance chip, and an AR nuclear translocation assay. Discussion This study documents that PFCs have a substantial impact on human health as they interfere with hormonal pathways, potentially leading to male infertility.

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