Calcium signaling in oocyte quality and functionality and its application.

Calcium (Ca2+) is a second messenger for many signal pathways, and changes in intracellular Ca2+ concentration ([Ca2+]i) are an important signaling mechanism in the oocyte maturation, activation, fertilization, function regulation of granulosa and cumulus cells and offspring development. Ca2+ oscillations occur during oocyte maturation and fertilization, which are maintained by Ca2+ stores and extracellular Ca2+ ([Ca2+]e). Abnormalities in Ca2+ signaling can affect the release of the first polar body, the first meiotic division, and chromosome and spindle morphology. Well-studied aspects of Ca2+ signaling in the oocyte are oocyte activation and fertilization. Oocyte activation, driven by sperm-specific phospholipase PLCζ, is initiated by concerted intracellular patterns of Ca2+ release, termed Ca2+ oscillations. Ca2+ oscillations persist for a long time during fertilization and are coordinately engaged by a variety of Ca2+ channels, pumps, regulatory proteins and their partners. Calcium signaling also regulates granulosa and cumulus cells' function, which further affects oocyte maturation and fertilization outcome. Clinically, there are several physical and chemical options for treating fertilization failure through oocyte activation. Additionally, various exogenous compounds or drugs can cause ovarian dysfunction and female infertility by inducing abnormal Ca2+ signaling or Ca2+ dyshomeostasis in oocytes and granulosa cells. Therefore, the reproductive health risks caused by adverse stresses should arouse our attention. This review will systematically summarize the latest research progress on the aforementioned aspects and propose further research directions on calcium signaling in female reproduction.

Profile of Polyphenols, Fatty Acids, and Terpenes in Henola Hemp Seeds Depending on the Method of Fertilization.

Botanical varieties of hemp differ in chemical composition, plant morphology, agronomy, and industrial suitability. Hemp is popular for cultivation for the production of cannabinoid oil, fiber production, biomass, etc. The fertilization process is one of the most important factors affecting the plant, both its condition and chemical composition. So far, research has been carried out proving that hemp is a valuable source of, among others: fatty acids, amino acids, acids, vitamins, numerous micro- and macroelements, and antioxidant compounds. In this experiment, it was decided to check the possibility of harvesting hemp panicles twice in one year. The purpose of this treatment is to use one plant to produce cannabidiol oil and grain. The main aim of the research was to determine bioactive compounds in hemp seeds and to determine whether the cultivation method affects their content and quantity. Based on the research conducted, it was observed that hemp can be grown in two directions at the same time and harvested twice because its health-promoting properties do not lose their value. It was found that regardless of whether hemp is grown solely for seeds or to obtain essential oils and then seeds, the type of fertilization does not affect the content of phenolic acids (e.g., syringic acid: 69.69-75.14 µg/100 g, vanillic acid: 1.47-1.63 µg/100 g). Based on the conducted research, it was found that essential oils can be obtained from one plant in the summer and seeds from Henola hemp cultivation in the autumn, because such a treatment does not affect the content of the discussed compounds.

The Effect of Synthetic Polyamine BPA-C8 on the Fertilization Process of Intact and Denuded Sea Urchin Eggs.

Sea urchin eggs are covered with layers of extracellular matrix, namely, the vitelline layer (VL) and jelly coat (JC). It has been shown that sea urchin eggs' JC components serve as chemoattractants or ligands for the receptor on the fertilizing sperm to promote the acrosome reaction. Moreover, the egg's VL provides receptors for conspecific sperm to bind, and, to date, at least two sperm receptors have been identified on the surface of sea urchin eggs. Interestingly, however, according to our previous work, denuded sea urchin eggs devoid of the JC and VL do not fail to become fertilized by sperm. Instead, they are bound and penetratedby multiple sperm, raising the possibility that an alternative pathway independent of the VL-residing sperm receptor may be at work. In this research, we studied the roles of the JC and VL using intact and denuded eggs and the synthetic polyamine BPA-C8. BPA-C8 is known to bind to the negatively charged macromolecular complexes in the cells, such as the JC, VL, and the plasma membrane of echinoderm eggs, as well as to the actin filaments in fibroblasts. Our results showed that, when added to seawater, BPA-C8 significantly repressed the Ca2+ wave in the intact P. lividus eggs at fertilization. In eggs deprived of the VL and JC, BPA-C8 binds to the plasma membrane and increases fibrous structures connecting microvilli, thereby allowing the denuded eggs to revert towards monospermy at fertilization. However, the reduced Ca2+ signal in denuded eggs was nullified compared to the intact eggs because removing the JC and VL already decreased the Ca2+ wave. BPA-C8 does not cross the VL and the cell membrane of unfertilized sea urchin eggs to diffuse into the cytoplasm at variance with the fibroblasts. Indeed, the jasplakinolide-induced polymerization of subplasmalemmal actin filaments was inhibited in the eggs microinjected with BPA-C8, but not in the ones bath-incubated with the same dose of BPA-C8.

Transcriptomic landscape of seedstick in Arabidopsis thaliana funiculus after fertilisation.

BACKGROUND: In Angiosperms, the continuation of plant species is intricately dependent on the funiculus multifaceted role in nutrient transport, mechanical support, and dehiscence of seeds. SEEDSTICK (STK) is a MADS-box transcription factor involved in seed size and abscission, and one of the few genes identified as affecting funiculus growth. Given the importance of the funiculus to a correct seed development, allied with previous phenotypic observations of stk mutants, we performed a transcriptomic analysis of stk funiculi from floral stage 17, using RNA-sequencing, to infer on the deregulated networks of genes. RESULTS: The generated dataset of differentially expressed genes was enriched with cell wall biogenesis, cell cycle, sugar metabolism and transport terms, all in accordance with stk phenotype observed in funiculi from floral stage 17. We selected eight differentially expressed genes for transcriptome validation using qPCR and/or promoter reporter lines. Those genes were involved with abscission, seed development or novel functions in stk funiculus, such as hormones/secondary metabolites transport. CONCLUSION: Overall, the analysis performed in this study allowed delving into the STK-network established in Arabidopsis funiculus, fulfilling a literature gap. Simultaneously, our findings reinforced the reliability of the transcriptome, making it a valuable resource for candidate genes selection for functional genetic studies in the funiculus. This will enhance our understanding on the regulatory network controlled by STK, on the role of the funiculus and how seed development may be affected by them.

Heat stress mediates toxicity of rutile titanium dioxide nanoparticles on fertilisation capacity in the broadcast spawning mussel Mytilus galloprovincialis.

Titanium dioxide nanoparticle (nTiO2) pollution of marine environments is rapidly increasing with potentially deleterious effects on wildlife. Yet, the impacts of nTiO2 on reproduction remain poorly understood. This is especially the case for broadcast spawners, who are likely to be more severely impacted by environmental disturbances because their gametes are directly exposed to the environment during fertilisation. In addition, it is unclear whether rising water temperatures will further exacerbate the impact of nTiO2 toxicity. Here, in a series of fertilisation trials, we systematically examine the main and interactive effects of nTiO2 exposure and seawater temperature on fertilisation success in the Mediterranean mussel Mytilus galloprovincialis. Specifically, our fertilisation trials explored whether nTiO2 exposure influences fertilisation rates when (i) eggs alone are exposed, (ii) both sperm and eggs are exposed simultaneously, and (iii) whether increases in seawater temperature interact with nTiO2 exposure to influence fertilisation rates. We also ask whether changes in nTiO2 concentrations influence key sperm motility traits using computer-assisted sperm analysis (CASA). In fertilisation trials for treatment groups (i) and (ii), we found no main effects of nTiO2 at environmentally relevant concentrations of 5, 10 and 50 µg L-1 on fertilisation capacity relative to the control. Consistent with these findings, we found no effect of nTiO2 exposure on sperm motility. However, in treatment group (iii), when fertilisation trials were conducted at higher temperatures (+6 °C), exposure of gametes from both sexes to 10 µg L-1 nTiO2 led to a reduction in fertilisation rates that was significantly greater than when gametes were exposed to elevated temperature alone. These interacting effects of nTiO2 exposure and seawater temperature demonstrate the toxic potential of nTiO2 for fertilisation processes in a system that is likely to be impacted heavily by predicted future increases in sea surface temperatures.

Demographic drivers of reproductive failure in a threatened bird: Insights from a decade of data.

Hatching failure affects up to 77% of eggs laid by threatened bird species, yet the true prevalence and drivers of egg fertilization failure versus embryo mortality as underlying mechanisms of hatching failure are unknown. Here, using ten years of data comprising 4,371 eggs laid by a population of a threatened bird, the hihi (Notiomystis cincta), we investigate the relative importance of infertility and embryo death as drivers of hatching failure and explore population-level factors associated with them. We show that of the 1,438 eggs that failed to hatch (33% of laid eggs) between 2010 and 2020, 83% failed due to embryo mortality, with the majority failing in the early stages of embryonic development. In the most comprehensive estimates of infertility rates in a wild bird population to date, we find that fertilization failure accounts for around 17% of hatching failure overall and is more prevalent in years where the population is smaller and more male biased. Male embryos are more likely to die during early development than females, but we find no overall effect of sex on the successful development of embryos. Offspring fathered by within-pair males have significantly higher inbreeding levels than extra-pair offspring; however, we find no effect of inbreeding nor extra-pair paternity on embryo mortality. Accurately distinguishing between infertility and embryo mortality in this study provides unique insight into the underlying causes of reproductive failure over a long-term scale and reveals the complex risks of small population sizes to the reproduction of threatened species.

Effect of naringenin on post-thaw quality, fertility-associated gene expression and fertilization potential of buffalo (Bubalus bubalis) bull sperm.

Our objectives were to explore the effect of naringenin addition in the semen extender on the post-thaw 1) sperm quality, 2) fertility-associated gene expression, and 3) fertilization potential of buffalo bull sperm. In experiment 1, semen samples (n = 32) from four Nili-Ravi buffalo bulls were pooled (n = 8) and diluted with the tris-citric acid (TCF-EY) extender containing different concentrations of naringenin, i.e., placebo (DMSO), 0 (control), 50, 100, 150 and 200 µM naringenin. After dilution, semen samples were packed in 0.5 mL French straws, cryopreserved and analyzed for post-thawed sperm quality and gene expression. Computer-assisted Semen Analysis, Hypo-osmotic Swelling test, Normal Apical Ridge assay, Rhodamine 123, Acridine orange, Propidium iodide staining and Thiobarbituric Acid Reactive Substances assay were performed to assess sperm motility parameters, plasma membrane functionality, acrosome integrity, mitochondrial membrane potential, DNA integrity, viability and lipid peroxidation, respectively. Expression levels of sperm acrosome-associated SPACA3, DNA condensation-related PRM1, anti-apoptotic BCL2, pro-apoptotic BAX, and oxidative stress-associated ROMO1 genes were evaluated through qPCR. Results revealed that total and progressive motility, plasma membrane functionality, acrosome integrity, mitochondrial membrane potential, DNA integrity and viability were higher (P < 0.05) with 50, 100 and 150 µM naringenin compared to 200 µM naringenin, placebo and control groups. Moreover, all naringenin-treated groups improved catalase activity, and reduced lipid peroxidation compared to placebo and control groups (P < 0.05). Relative expression levels of SPACA3 and PRM1 genes were higher (P < 0.05) with 150 µM naringenin compared to all groups except 100 µM (P > 0.05). No difference (P > 0.05) in the expression level of BCL2 gene was observed among all groups. Furthermore, BAX gene was expressed higher (P < 0.05) in the 200 µM naringenin group, whereas no difference (P > 0.05) in expression was noticed among the remaining groups. In addition, ROMO1 gene was expressed lower (P < 0.05) in all naringenin-treated groups compared to the control. In experiment 2, the in vivo fertility of semen doses (n = 400; 200/group) containing optimum concentration of naringenin (150 µM; depicted better in vitro sperm quality in experiment 1) was compared with control during the breeding season. Buffaloes were inseminated 24 h after the onset of natural estrus and palpated transrectal for pregnancy at least 60 days post-insemination. The fertility rate of 150 µM naringenin group was higher (P = 0.0366) compared to the control [57.00 ± 0.03 % (114/200) vs. 46.50 ± 0.04 % (93/200), respectively]. Taken together, it is concluded that naringenin supplementation in semen extender improves post-thaw quality, fertility-associated gene expression and fertilization potential of buffalo bull sperm, more apparently at 150 µM concentration.

Switching on lysosomes.

The formation of large endolysosomal structures in unfertilized eggs ensures that lysosomes remain dormant before fertilization, and then shift into clean-up mode after the egg-to-embryo transition.

In vivo induction of male sexual behavior in zebrafish by adding agents to water.

Successful fertilization in fish mating occurs when egg maturation in the ovary of the female, ovulation, sperm maturation in the testis of the male, and reproductive behaviors in both sexes are triggered in synchrony. The male sexual behavior of fish is induced by hormones and pheromones. In a previous study, we demonstrated that externally applied hormones added to the water can induce oocyte maturation and ovulation in female zebrafish. Here, we attempted to establish a similar method to induce the sexual behavior of male zebrafish. The male sex steroid testosterone (Tes) triggered sexual behavior within several hours in vivo when administered directly into the surrounding water. A selective agonist for membrane progesterone receptor (mPR), Org OD-02 (Org), also induced sexual behavior. Through trials of various combinations of compounds, we found that the most effective conditions were achieved by treatment with a mixture of testosterone (Tes) and Org. The effect of treatment was evaluated by the number of fertilized eggs obtained by pairing with females with induced ovulation in vivo. The period necessary for the induction of male sexual behavior was evaluated by time course experiments. The success rate of mating and the number of fertilized eggs reached the maximum level at 3-4 hours of treatment. The duration of hormonal treatment was confirmed by counting the number of hooking occurrences, which is the final cue to induce spawning by females. In summary, we have established a method to induce male sexual behavior in zebrafish in vivo. The method can be used to obtain fertilized eggs in zebrafish by simply adding agents into the water.

Investigations into the role of platelet-activating factor in the peri-conception period of the mare.

In Brief: In many mammals, the lipid platelet-activating factor (PAF) has important functions in female reproduction and fertility. This study shows that PAF is present in the reproductive tissues of mares and is involved in processes related to ovulation and early pregnancy. Abstract: Platelet-activating factor (PAF) has been implicated in a number of reproductive processes ranging from ovulation to embryo motility but has not been widely explored in the mare. To identify the presence and examine the role of PAF in the equine periconception processes, targeted mass spectrometry coupled with chromatographic separation was performed on equine follicular fluid (FF), and PAF was quantitatively detected. Subsequently, untargeted high-resolution mass spectrometry-based lipidomic analysis was carried out to quantify PAF in different-sized pre-ovulatory follicles, whereby different molecular species of PAF, PAF (14:0) and PAF (16:1), were both seen to be increasing with follicle diameter. These findings suggest that PAF within FF is increasing as preovulatory follicles approach ovulation. Additionally, immunofluorescence staining identified the PAF receptor in the luminal pericellular, apical, and basal aspect of equine oviductal epithelial cells. Lastly, an equine oviductal epithelial organoid model was generated and showed that the addition of PAF significantly increased the ciliary beat frequency (CBF) (Hz), an action consistent with a role for PAF in embryo migration. It is proposed that the local action of PAF on the ciliated cells of the oviduct propels both the oocyte and the conceptus towards the uterus. In the mare, it appears that PAF is a contributor during the periconception period, potentially being a mediator in the mechanisms of ovulation and in the dialogue of very early pregnancy.

In Vivo Visualization of Calcium Transients during Fertilization and Early Development in C. elegans.

Calcium is an important signaling molecule during the oocyte-to-embryo transition (OET) and early embryogenesis. The hermaphroditic nematode Caenorhabditis elegans provides several unique advantages for the study of the OET as it is transparent and has an ordered gonad that produces one mature oocyte every ~23 min at 20 °C. We have modified the genetically encoded calcium indicator jGCaMP7s to fluorescently indicate the moment of fertilization within a living organism. We have termed this reporter "CaFE" for Calcium during Fertilization in C. elegans. The CaFE reporter was engineered into a safe harbor locus in single copy, has no significant impact on physiology or fecundity, and produces a robust signal upon fertilization. Here, a series of protocols is presented for utilizing the CaFE reporter as an in vivo tool for dissecting the OET and embryogenesis. We include methods to synchronize worms, examine the effects of RNAi knockdown, mount worms for imaging, and to visualize calcium in oocytes and embryos. Additionally, we present the generation of additional worm strains to aid in this type of analysis. Demonstrating the utility of the CaFE reporter to visualize the timing of fertilization, we report that double ovulation occurs when ipp-5 is targeted by RNAi and that only the first oocyte undergoes immediate fertilization. Furthermore, the discovery of single-cell calcium transients during early embryogenesis is reported here, demonstrating that the CaFE reporter persists into early development. Importantly, the CaFE reporter in worms is simple enough to use for incorporation into course-based undergraduate research (CURE) laboratory classes. The CaFE reporter, coupled with the ordered gonad and ease of RNAi in worms, facilitates inquiry into the cell-cell dynamics required to regulate internal fertilization and early embryogenesis.

Conception, pregnancy, and childbirth from the perspective of transgender men: A meta-ethnography.

BACKGROUND: Transgender men who decide to gestate biologically often face a health system that is highly feminized and discriminatory. In addition, the lack of preparation and knowledge among healthcare professionals leads to the provision of care that fails to meet their specific needs. AIM: To synthesise the experiences of transgender men with regard to conception, pregnancy, and childbirth. METHOD: Ten studies were included in a synthesis of qualitative studies, following the interpretive meta-ethnography method developed by Noblit and Hare and summarized in accordance with the eMERGe meta-ethnography reporting guidelines. RESULTS: The metaphor of a divergent matryoshka dealing with a constricted reality helps us to understand the experiences of conception, pregnancy, and childbirth of transgender men, who often face stigma, discrimination, and marginalization in society and healthcare. The metaphor also highlights the gender dysphoria that arises from the physical changes associated with these processes. Four key themes emerge from this metaphor: (1) The decision to conceive being a trans man; (2) The challenge of adjusting to a new body reality; (3) The significance of navigating in an environment of non-representation; and (4) The marked absence of transsexuality in mainstream healthcare. CONCLUSIONS: Actions should prioritize strengthening ethical sensitivities and improve the training of health professionals to address issues such as gender perspectives, equality, and communication skills. Additionally, social visibility policies need to be implemented.

Anti-Mullerian Hormone Assessment in Assisted Reproductive Technique Outcome and Natural Conception.

In recent years, the prevalence of infertility has increased, and appears to affect approximately one in six couples. Some of them must perform assisted reproductive techniques (ART) in order to achieve pregnancy. As a result, growing interest has arisen about predictive factors of pregnancy and live birth with and without ART. Anti-Mullerian hormone (AMH) is a glycoprotein discovered in the 1950s in male embryonic sexual differentiation. Later, in 1984, its role in folliculogenesis was reported: secreted by granulosa cells, this hormone is involved in the regulation of the recruitment of primordial follicles and in follicular growth. AMH assays were developed for women in 1990s, and the serum AMH level has rapidly become a crucial element in managing women's fertility. Based mainly on its ability to be a quantitative but indirect marker of ovarian reserve, the serum AMH assay is widely used in reproductive medicine and ART. This review summarizes current knowledge of the AMH assessment in the field of reproductive medicine. We focus on the role of AMH level to predict spontaneous pregnancy occurrence, ART outcomes, and fertility preservation outcomes.

Coevolution between eggs and sperm of insects.

Sexual selection is known to play a major role in the evolution of insect sperm size, whereas natural selection is thought to be a major driver of insect egg size. Despite these differing forms of selection operating, it is possible coevolution between male and female gametes can occur owing to their vital interactions during fertilization. We tested egg-sperm coevolution in insects and found that longer sperm correlated to longer and wider eggs. Moreover, the size of the entry point of sperm into insect eggs (micropyles), was positively related to the diameter of sperm, on average being approximately three times the diameter of the sperm. This suggests a function in reducing and channelling sperm entry, but potentially still leaving space for movement. Our work suggests that greater attention needs to be paid to egg-sperm interactions prior to the point of fertilization as they may influence the evolution of gametes.

Katanin, kinesin-13, and ataxin-2 inhibit premature interaction between maternal and paternal genomes in C. elegans zygotes.

Fertilization occurs before the completion of oocyte meiosis in the majority of animal species and sperm contents move long distances within the zygotes of mouse and C. elegans. If incorporated into the meiotic spindle, paternal chromosomes could be expelled into a polar body resulting in lethal monosomy. Through live imaging of fertilization in C. elegans, we found that the microtubule disassembling enzymes, katanin and kinesin-13 limit long-range movement of sperm contents and that maternal ataxin-2 maintains paternal DNA and paternal mitochondria as a cohesive unit that moves together. Depletion of katanin or double depletion of kinesin-13 and ataxin-2 resulted in the capture of the sperm contents by the meiotic spindle. Thus limiting movement of sperm contents and maintaining cohesion of sperm contents within the zygote both contribute to preventing premature interaction between maternal and paternal genomes.

Ambient air pollution decreased normal fertilization rate via the mediation of seminal prosaposin.

OBJECTIVE: This study focuses on the association between seminal concentration of prosaposin and ambient air pollutants and whether the association affects the normal fertilization rate in vitro fertilization (IVF) treatment. METHODS: The cohort of 323 couple participants aged 22-46 was recruited from Jan. 2013 to Jun. 2018. At enrollment, resident address information was obtained and semen parameters of male counterparts were evaluated according to WHO criteria. We used inverse distance weighting interpolation to estimate the levels of ambient pollutants (SO2, O3, CO, NO2, PM2.5, and PM10) in the surrounding area. The exposure of each participant was estimated based on the data gathered from air quality monitoring stations and their home address over various periods (0-9, 10-14, and 0-90 days) before semen sampling. The generalized linear regression model (GLM) and the Bayesian kernel machine regression (BKMR) were used to analyze the associations between pollutants, semen parameters, prosaposin, and normal fertilization. Additionally, the mediating effect of prosaposin and semen parameters on the link between pollutants and normal fertilization was investigated. RESULTS: GLM and BKMR showed exposure to ambient air pollutants was all associated with the concentration of seminal prosaposin, among them, O3 and CO were also associated with normal fertilization (-0.10, 95 %CI: -0.13, -0.06; -26.43, 95 %CI: -33.79, -19.07). Among the semen parameters, only the concentration of prosaposin and total motile sperm count (TMC) was associated with normal fertilization (0.059, 95 %CI: 0.047, 0.071; 0.016, 95 %CI: 0.012, 0.020). Mediation analysis showed that prosaposin played a stronger mediating role than TMC in the relationship between short-term exposure to O3 and fertilization (66.83 %, P<0.001 versus 3.05 %, P>0.05). CONCLUSION: Seminal plasma prosaposin showed a stronger meditating effect reflect the correlation between ambient air pollutants and normal fertilization rate than conventional semen parameters, which may be used as one of the indicators between pollution and fertilization in IVF.

Genetic relationship of energy balance predicted from milk traits with fertility in Japanese Holsteins.

We predicted the energy balance of cows from milk traits and estimated the genetic correlations of predicted energy balance (PEB) with fertility traits for the first three lactations. Data included 9,646,606 test-day records of 576,555 Holstein cows in Japan from 2015 to 2019. Genetic parameters were estimated with a multiple-trait model in which the records among lactation stages and parities were treated as separate traits. Fertility traits were conception rate at first insemination (CR), number of inseminations (NI), and days open (DO). Heritability estimates of PEB were 0.28-0.35 (first lactation), 0.15-0.29 (second), and 0.09-0.23 (third). Estimated genetic correlations among lactation stages were 0.85-1.00 (first lactation), 0.73-1.00 (second), and 0.64-1.00 (third). Estimated genetic correlations among parities were 0.82-0.96 (between first and second), 0.97-0.99 (second and third), and 0.69-0.92 (first and third). Estimated genetic correlations of PEB in early lactation with fertility were 0.04 to 0.19 for CR, -0.03 to -0.19 for NI, and -0.01 to -0.24 for DO. Genetic improvement of PEB is possible. Lower PEB in early lactation was associated with worse fertility, suggesting that improving PEB in early lactation may improve reproductive performance.

Patterns of paternal medication dispensation around the time of conception.

BACKGROUND: Past research on the safety of prenatal exposure to medications has focused on maternal use during gestation, with limited research into the potential effects of paternal use during the spermatogenic period preceding conception. Knowing the most common medications used by fathers around the time of conception can inform research priorities in this field. OBJECTIVES: To identify the most common medications dispensed to fathers in the preconception period. METHODS: Within the MarketScan research database of commercially insured individuals in the United States from 2011 to 2020, we identified pregnancies, estimated the date of conception, linked each pregnancy to the father using family enrolment information and required minimum enrolment period and prescription benefits. Then, we described the use of prescription medications by the father during the 90 days before conception based on pharmacy dispensation claims. RESULTS: Of 4,437,550 pregnancies, 51.6% were linked with a father. Among the 1,413,762 pregnancies connected with a father that also met the inclusion criteria, the most common classes of medications dispensed were psychotropics (8.66%), antibiotics (7.21%), and analgesics (6.82%). The most frequently dispensed medications were amoxicillin (3.75%), azithromycin (3.15%), fluticasone (2.70%) and acetaminophen/hydrocodone (2.70%). Some fathers filled prescriptions for medications associated with foetal embryopathy when used by the mother, including mycophenolate (0.04%), methotrexate (0.03%) and isotretinoin (0.02%). CONCLUSIONS: More than a third of fathers filled at least one prescription medication in the preconception period, and several of them are known to be embryotoxic, emphasizing the necessity for further investigation into the potential teratogenicity of paternal exposure.

Exposure of women undergoing in-vitro fertilization to per-and polyfluoroalkyl substances: Evidence on negative effects on fertilization and high-quality embryos.

In April 2023, the World Health Organization (WHO) reported that 17.5% of the global adult population experience infertility. What may be the contribution of per-and polyfluoroalkyl (PFAS) to this global public health problem? This study explored the associations between in vitro fertilization (IVF) outcomes and plasma concentrations of individual PFAS and PFAS mixtures in women undergoing in vitro fertilization and embryo transfer (IVF-ET) and how these exposures might affect IVF outcomes. We analyzed 8 PFASs in plasma samples from women (N = 259) who underwent IVF treatment. In multivariable generalized linear mixed models, there were statistically significant associations of higher plasma concentrations of PFNA with reduced numbers of total retrieved oocytes [12.486 (95%CI: 0.446,25.418), p trend = 0.017], 2 PN zygotes [6.467(95%CI: 2.034,14.968), p trend = 0.007], and cleavage embryos [6.039(95%CI: 2.162,14.240), p trend = 0.008]. Similarly, there was a continuous decline in the numbers of retrieved 2 PN zygotes and cleavage embryos with increasing concentration of PFOS [6.467(95%CI: 2.034,14.968), p trend = 0.009 and 6.039(95%CI: 2.162,14.240), p trend = 0.031,respectively] and a negative association between PFHxS concentrations and clinical pregnancy during the initial cycles of frozen ET [0.525(95%CI:0.410,0.640), p trend = 0.021]. To investigate the joint effect of PFAS mixtures, a confounder-adjusted BKMR model analysis showed inverse relationship between PFAS mixtures and the number of high-quality embryos, 2 PN zygotes and cleavage embryos, to which the greatest contributors to the mixture effect are PFDeA and PFBS, respectively. It demonstrated that PFAS exposure might exert negative effects on oocyte yield, fertilization and high-quality embryo in women undergoing IVF. These findings suggest that exposure to PFAS may increase the risk of female infertility and further studies are needed to uncover the potential mechanisms underlying the reproductive effects associated with PFAS.