- Proceedings of the National Academy of Sciences of the United States of America
- Published almost 4 years ago
The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.
An important problem in reproductive medicine is deciding when people who have failed to become pregnant without medical assistance should begin investigation and treatment. This study describes a computational approach to determining what can be deduced about a couple’s future chances of pregnancy from the number of menstrual cycles over which they have been trying to conceive. The starting point is that a couple’s fertility is inherently uncertain. This uncertainty is modelled as a probability distribution for the chance of conceiving in each menstrual cycle. We have developed a general numerical computational method, which uses Bayes' theorem to generate a posterior distribution for a couple’s chance of conceiving in each cycle, conditional on the number of previous cycles of attempted conception. When various metrics of a couple’s expected chances of pregnancy were computed as a function of the number of cycles over which they had been trying to conceive, we found good fits to observed data on time to pregnancy for different populations. The commonly-used standard of 12 cycles of non-conception as an indicator of subfertility was found to be reasonably robust, though a larger or smaller number of cycles may be more appropriate depending on the population from which a couple is drawn and the precise subfertility metric which is most relevant, for example the probability of conception in the next cycle or the next 12 cycles. We have also applied our computational method to model the impact of female reproductive ageing. Results indicate that, for women over the age of 35, it may be appropriate to start investigation and treatment more quickly than for younger women. Ignoring reproductive decline during the period of attempted conception added up to two cycles to the computed number of cycles before reaching a metric of subfertility.
- Journal of the American Board of Family Medicine : JABFM
- Published over 4 years ago
In recent years there has been an explosion in the development of medical apps, with more than 40,000 apps now available. Nearly 100 apps allow women to track their fertility and menstrual cycles and can be used to avoid or achieve pregnancy. Apps offer a convenient way to track fertility biomarkers. However, only some use evidence-based fertility awareness-based methods (FABMs), which with ideal use have rates of effectiveness similar to those of commonly used forms of hormonal birth control. Since having a baby or preventing a pregnancy are important responsibilities, it is critical that women and couples have access to reliable, evidence-based apps that allow them to accurately track their fertility.
Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12), and a different group of females (nC group; N = 12) not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures) with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation), activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual expectation. Results may provide a basis for future imaging studies on sexual processing in females, especially in the context of less explicit erotic stimulation.
The aim of the present study was to explore the prospective relationship between anxiety symptoms and coping strategies during late pregnancy and early postpartum.
Trisomy 9 can be suspected and confirmed in the prenatal period since the 11-13.6 weeks of screening. In cases of partial trisomy 9, the diagnosis is important especially to counseling the couple due to the increased likelihood of recurrence in subsequent pregnancies.
We sought to compare diagnostic values of two-dimensional transvaginal sonography (2D TVS) and office hysteroscopy (OH) for evaluation of endometrial pathologies in cases with repeated implantation failure (RIF) or recurrent pregnancy loss (RPL).
- CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
- Published over 3 years ago
Death by suicide during the perinatal period has been understudied in Canada. We examined the epidemiology of and health service use related to suicides during pregnancy and the first postpartum year.
An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue’s cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation. We show that Rac1 is crucial for mammary alveolar epithelia to switch from secretion to a phagocytic mode and rapidly remove dying neighbors. Moreover, Rac1 restricts the extrusion of dying cells into the lumen, thus promoting their eradication by live phagocytic neighbors while within the epithelium. Without Rac1, residual milk and cell corpses flood the ductal network, causing gross dilation, chronic inflammation, and defective future regeneration.
Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.