Fertility Of Offspring Research Articles

Commentary: In Utero Exposure to Metformin Reduces the Fertility of Male Offspring in Adulthood.

Commentary: In Utero Exposure to Metformin Reduces the Fertility of Male Offspring in Adulthood.

Investigation of spermiotoxic, embryotoxic and cytotoxic effects of copper pyrithione on Paracentrotus lividus (Lamarck, 1816)

Spermiotoxic, embryotoxic and cytotoxic effects of the widely used biofouling biocide copper pyrithione (CuPt) were evaluated in bioassays to examine the inhibition of fertilization rate, offspring quality and effects on early development of the sea urchin Paracentrotus lividus. CuPt was non-spermiotoxic for fertilization rates but the frequency of embryonic malformations increased in a concentration-dependent manner when eggs were fertilized with CuPt-exposed sperm. CuPt EC50 was calculated to be 13.58 ?g/l for embryotoxicity. While the frequency of normally developed plutei decreased, the number of larvae with skeletal deformations increased. The IC25 and IC50 values in cytotoxicity assays were calculated to be 12.79 and 47.85 ?g/l, respectively. The study revealed statistically significant decrease in the number of mitotically dividing cells, increase in the percentage of interphase cells and increased chromosomal abnormalities in the exposed cells. According to these results, CuPt can be said to have a highly toxic effect on sea urchin embryos at the applied concentrations. This situation suggests that there may be a potential risk of marine contamination with CuPt for this species.

Maternal immune activation affects male offspring fertility, sperm quality and small RNA profile

Maternal immune activation affects male offspring fertility, sperm quality and small RNA profile

Frontiers in sheep reproduction - making use of natural responses to environmental challenges to manage productivity.

This review addresses advances, directions and opportunities for research on sheep reproduction in the context of the global challenges of food security and climate change, and demand for 'clean, green and ethical' (CGE) animal management. The foundation of CGE management is an understanding of the physiological processes through which the reproductive system responds to changes in the animal's environment. These days, to the main environmental factors (photoperiod, nutrition, pheromones), we need to add stress from extreme weather events. With respect to nutrition in rams, we now have a deeper understanding of the responses of the brain centres that control gonadotrophin secretion (the kisspeptin system). At testis level, we have found that nutrition affects non-coding RNAs in Sertoli cells and germ cells, thus affecting the balance between cell proliferation and apoptosis. This proliferation-apoptosis balance is also affected during prenatal development, when undernutrition or stress in pregnant ewes seems to elicit epigenetic changes in developing gonads that could affect offspring fertility in adult life. With respect to nutrition in ewes, metabolic signals act directly on ovarian follicles, and thus change ovulation rate, but the variety of signals now includes the adipokines. An early concern was that nutritional supplements that increase ovulation rate would also increase embryo mortality but we now know that embryo survival is improved under field conditions. Finally, we had always thought that the efficiency gains from early puberty in lambs could only be achieved by accelerating fat accumulation, but we now know that faster muscle growth will achieve the same goal, offering two advantages in meat production systems. With respect to pheromones ('ram effect'), we have a deeper understanding of the brain responses (kisspeptin system) but, most importantly, a realization that the response of ewes to the ram signal involves cell division in memory centres. Many opportunities remain.

In Utero Exposure to Metformin Reduces the Fertility of Male Offspring in Adulthood.

Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance. Metformin is also used in the treatment of pregnancy disorders such as gestational diabetes. However, the consequences of foetal exposure to metformin on the fertility of exposed offspring remain poorly documented. In this study, we investigated the effect of in utero metformin exposure on the fertility of female and male offspring. We observed that metformin is detectable in the blood of the mother and in amniotic fluid and blood of the umbilical cord. Metformin was not measurable in any tissues of the embryo, including the gonads. The effect of metformin exposure on offspring was sex specific. The adult females that had been exposed to metformin in utero presented no clear reduction in fertility. However, the adult males that had been exposed to metformin during foetal life exhibited a 30% reduction in litter size compared with controls. The lower fertility was not due to a change in sperm production or the motility of sperm. Rather, the phenotype was due to lower sperm head quality – significantly increased spermatozoa head abnormality with greater DNA damage – and hypermethylation of the genomic DNA in the spermatozoa associated with lower expression of the ten-eleven translocation methylcytosine dioxygenase 1 (TET1) protein. In conclusion, while foetal metformin exposure did not dramatically alter gonad development, these results suggest that metabolic modification by metformin during the foetal period could change the expression of epigenetic regulators such as Tet1 and perturb the genomic DNA in germ cells, changes that might contribute to a reduced fertility.

Granulocyte Colony-Stimulating Factor Restored Impaired Spermatogenesis and Fertility in an AML-Chemotherapy Mice Model.

Leukemia and treatment of male patients with anticancer therapy (aggressive chemotherapy and/or radiotherapy) may lead to infertility or even permanent male sterility. Their mechanisms of spermatogenesis impairment and the decrease in male fertility are not yet clear. We showed that under acute myeloid leukemia (AML) conditions, alone and in combination with cytarabine (CYT), there was significant damage in the histology of seminiferous tubules, a significant increase in apoptotic cells of the seminiferous tubules, and a reduction in spermatogonial cells (SALL and PLZF) and in meiotic (CREM) and post-meiotic (ACROSIN) cells. In addition, we showed a significant impairment in sperm parameters and fertilization rates and offspring compared to control. Our results showed a significant decrease in the expression of glial cell line-derived neurotrophic factor (GDNF), macrophage colony-stimulating factor (MCSF) and stem cell factor (SCF) under AML conditions, but not under cytarabine treatment compared to control. In addition, our results showed a significant increase in the pro-inflammatory cytokine interleukin-1 (IL-1) alpha in whole testis homogenates in all treatment groups compared to the control. Increase in IL-1 beta level was shown under AML conditions. We identified for the first time the expression of GCSF receptor (GCSFR) in sperm cells. We showed that GCSF injection in combination with AML and cytarabine (AML + CYT + GCSF) extended the survival of mice for a week (from 6.5 weeks to 7.5 weeks) compared to (AML + CYT). Injection of GCSF to all treated groups (post hoc), showed a significant impact on mice testis weight, improved testis histology, decreased apoptosis and increased expression of pre-meiotic, meiotic and post- meiotic markers, improved sperm parameters, fertility capacity and number of offspring compared to the controls (without GCSF). GCSF significantly improved the spermatogonial niche expressed by increased the expression levels of testicular GDNF, SCF and MCSF growth factors in AML-treated mice and (AML + CYT)-treated mice compared to those groups without GCSF. Furthermore, GCSF decreased the expression levels of the pro-inflammatory cytokine IL-12, but increased the expression of IL-10 in the interstitial compartment compared to the relevant groups without GCSF. Our results show for the first time the capacity of post injection of GCSF into AML- and CYT-treated mice to improve the cellular and biomolecular mechanisms that lead to improve/restore spermatogenesis and male fertility. Thus, post injection of GCSF may assist in the development of future therapeutic strategies to preserve/restore male fertility in cancer patients, specifically in AML patients under chemotherapy treatments.

Effect of host switching simulation on the fitness of the gregarious parasitoid Anaphes flavipes from a novel two-generation approach

Herbivorous insects can escape the strong pressure of parasitoids by switching to feeding on new host plants. Parasitoids can adapt to this change but at the cost of changing their preferences and performance. For gregarious parasitoids, fitness changes are not always observable in the F1 generation but only in the F2 generation. Here, with the model species and gregarious parasitoid Anaphes flavipes, we examined fitness changes in the F1 generation under pressure from the simulation of host switching, and by a new two-generation approach, we determined the impact of these changes on fitness in the F2 generation. We showed that the parasitoid preference for host plants depends on hatched or oviposited learning in relation to the possibility of parasitoid decisions between different host plants. Interestingly, we showed that after simulation of parasitoids following host switching, in the new environment of a fictitious host plant, parasitoids reduced the fictitious host. At the same time, parasitoids also reduced fertility because in fictitious hosts, they are not able to complete larval development. However, from a two-generation approach, the distribution of parasitoid offspring into both native and fictitious hosts caused lower parasitoid clutch size in native hosts and higher individual offspring fertility in the F2 generation.

Clinical Guidelines for Sperm DNA Fragmentation (SDF) is Associated with Male Infertility from Reactive Oxygen Species (ROS)

Sperm DNA fragmentation is common in infertile male. Besides, sperm DNA integrity is essential for fertilization and healthy offspring development. Numerous genetic and environmental elements are associated with impacting sperm DNA integrity negatively. Such as lifestyle, ageing, industrial toxins, and infection. The mechanisms behind SDF are many, but apoptosis and reactive oxygen species are considered the main SDF mechanisms. The management of male infertility has led to the desire for more advanced SDF diagnostic tools to diagnose sperm DNA. Numerous sperm DNA damage assays such as terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) assay and in situ nick translation (ISNT) are available to enhance SDF diagnosing and ultimately to better SDF management. Clinical SDF can lead to a low pregnancy rate, defects in embryo development and impaired offspring health. Moreover, SDF can impact the effectiveness of assisted reproductive technology through transfer genetics impartment to the embryo b in vitro fertilization or intracytoplasmic sperm injection. SDF can be mange through lifestyle changing, treating existing infection in the male reproductive tract and reactive oxygen species.

Confirmation of GmPPR576 as a fertility restorer gene of cytoplasmic male sterility in soybean.

In soybean, heterosis achieved through the three-line system has been gradually applied in breeding to increase yield, but the underlying molecular mechanism remains unknown. We conducted a genetic analysis using the pollen fertility of offspring of the cross NJCMS1A×NJCMS1C. All the pollen of F1 plants was semi-sterile; in F2, the ratio of pollen-fertile plants to pollen-semi-sterile plants was 208:189. This result indicates that NJCMS1A is gametophyte sterile, and the fertility restoration of NJCMS1C to NJCMS1A is a quality trait controlled by a single gene locus. Using bulked segregant analysis, the fertility restorer gene Rf in NJCMS1C was located on chromosome 16 between the markers BARCSOYSSR_16_1067 and BARCSOYSSR_16_1078. Sequence analysis of genes in that region showed that GmPPR576 was non-functional in rf cultivars. GmPPR576 has one functional allele in Rf cultivars but three non-functional alleles in rf cultivars. Phylogenetic analysis showed that the GmPPR576 locus evolved rapidly with the presence of male-sterile cytoplasm. GmPPR576 belongs to the RFL fertility restorer gene family and is targeted to the mitochondria. GmPPR576 was knocked out in soybean N8855 using CRISPR/Cas9. The T1 plants showed sterile pollen, and T2 plants produced few pods at maturity. The results indicate that GmPPR576 is the fertility restorer gene of NJCMS1A.

Altered Follicular Fluid Metabolic Pattern Correlates with Female Infertility and Outcome Measures of In Vitro Fertilization.

Nearly 40–50% of infertility problems are estimated to be of female origin. Previous studies dedicated to the analysis of metabolites in follicular fluid (FF) produced contrasting results, although some valuable indexes capable to discriminate control groups (CTRL) from infertile females (IF) and correlate with outcome measures of assisted reproduction techniques were in some instances found. In this study, we analyzed in blind FF of 35 control subjects (CTRL = patients in which inability to obtain pregnancy was exclusively due to a male factor) and 145 IF (affected by: endometriosis, n = 19; polycystic ovary syndrome, n = 14; age-related reduced ovarian reserve, n = 58; reduced ovarian reserve, n = 29; unexplained infertility, n = 14; genetic infertility, n = 11) to determine concentrations of 55 water- and fat-soluble low molecular weight compounds (antioxidants, oxidative/nitrosative stress-related compounds, purines, pyrimidines, energy-related metabolites, and amino acids). Results evidenced that 27/55 of them had significantly different values in IF with respect to those measured in CTRL. The metabolic pattern of these potential biomarkers of infertility was cumulated (in both CTRL and IF) into a Biomarker Score index (incorporating the metabolic anomalies of FF), that fully discriminated CTRL (mean Biomarker Score value = 4.00 ± 2.30) from IF (mean Biomarker Score value = 14.88 ± 3.09, p < 0.001). The Biomarker Score values were significantly higher than those of CTRL in each of the six subgroups of IF. Posterior probability curves and ROC curve indicated that values of the Biomarker Score clustered CTRL and IF into two distinct groups, based on the individual FF metabolic profile. Furthermore, Biomarker Score values correlated with outcome measures of ovarian stimulation, in vitro fertilization, number and quality of blastocysts, clinical pregnancy, and healthy offspring. These results strongly suggest that the biochemical quality of FF deeply influences not only the effectiveness of IVF procedures but also the following embryonic development up to healthy newborns. The targeted metabolomic analysis of FF (using empowered Redox Energy Test) and the subsequent calculation of the Biomarker Score evidenced a set of 27 low molecular weight infertility biomarkers potentially useful in the laboratory managing of female infertility and to predict the success of assisted reproduction techniques.

P–766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages &amp; Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2–7.4] vs FET 5.8 [4.1–7.5] vs SC 6.5 [4.8–7.8]) and calcarine (fresh ET 13.5 [IQR 10.1–16.1] vs FET 14.5 [12.1–15.8] vs SC 16.4 [14.3–17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings: Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number Not applicable

P-766 Neurodevelopment in fetuses conceived by assisted reproductive technologies following fresh and frozen embryo transfer

Abstract Study question Do in vitro fertilization (IVF) offspring present different neurodevelopment assessed by fetal neurosonography and infant neurobehavioral tests as compared to those spontaneously conceived (SC)? Summary answer IVF offspring, especially those obtained after fresh embryo-transfer (ET), showed subtle structural differences in fetal neurosonography and poorer neurobehavioral scores at twelve months of age. What is known already The number of pregnancies following assisted reproductive technologies (ART) is currently increasing worldwide. Concerns about the neurodevelopment of subjects conceived by IVF have been rising and mostly studied in children and adolescents with inconsistent results. Many of the identified risk associations were only observed in subgroups or disappeared after adjustment for covariates, mainly multiple pregnancy and gestational age at birth. It is unknown whether fetal brain development and cortical folding differ prenatally in IVF fetuses as compared to SC. Study design, size, duration This is the first study examining fetal neurodevelopment by neurosonography in IVF fetuses. A prospective cohort study of 210 singleton pregnancies recruited from 2017 to 2020, including 70 SC gestations, 70 conceived by IVF following frozen ET (FET) and 70 IVF after fresh ET. Fetal neurosonography was performed in all pregnancies. Additionally, Ages &amp; Stages Questionnaires (ASQ) were obtained at 12 months of corrected age. Participants/materials, setting, methods IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. SC pregnancies were randomly selected from low-risk fertile couples and paired to IVF by maternal age. Fetal neurosonography including transvaginal approach was performed at 32±2 weeks of gestation, measured off-line by a single investigator and normalized by biparietal or occipitofrontal diameter. ASQ were obtained postnatally, at 12 months of corrected age. Main results and the role of chance Study groups were similar and comparable regarding maternal age, body mass index, study level and employment rate together with exposure to smoke, alcohol, aspirin and corticoids during pregnancy, gestational age (32±2 weeks) and estimated fetal weight (1700±400g) at neurosonography. As compared to SC pregnancies, both IVF populations showed differences in cortical development with reduced parieto-occipital (fresh ET 12.5mm [SD 2.5] vs FET 13.4 [2.6] vs SC 13.4 [2.6]), cingulate (fresh ET 5.8 [IQR 4.2-7.4] vs FET 5.8 [4.1-7.5] vs SC 6.5 [4.8-7.8]) and calcarine (fresh ET 13.5 [IQR 10.1-16.1] vs FET 14.5 [12.1-15.8] vs SC 16.4 [14.3-17.9]) sulci depth together with lower Sylvian fissure grading. Cortical development changes were more pronounced in the fresh ET group as compared to FET. Corpus callosum length and insula depth were lower in FET and fresh ET groups, respectively. Neurosonographic changes remained statistically significant after adjustment by ethnicity, gender, gestational age and weight centile at scan. IVF infants showed worse ASQ scores, especially in fresh ET for communication, personal-social, fine-motor and problem-solving skills. Gross-motor scores were significantly lower in FET as compared to SC and fresh ET. Differences were statistically significant after adjustment by maternal ethnicity, study level, employment status, breastfeeding, gender and corrected age. Limitations, reasons for caution The reported neurodevelopmental differences are subtle, with most neurosonographic findings lying within normal ranges. Infertility factors contribution to the outcome cannot be unraveled from the ART procedure itself. The milder features found in FET individuals cannot condition the techniqués choice and must be considered together with their global perinatal results. Wider implications of the findings Neurosonography is an appropriate tool to identify subtle brain differences between fetuses exposed and not exposed to ART. Prenatal features were consistent with postnatal neurobehavioral findings. These results support the relevance of a neurodevelopmental follow-up in IVF patients. Further studies are warranted to assess the long-term performance in these subjects. Trial registration number not applicable

Multigenerational consequences of aphid size on offspring phenotype and reproduction

AbstractIn many organisms, phenotype and fitness are strongly influenced by both current environmental factors and maternal effects. The low genetic variation, high phenotypic plasticity, and telescoping generations seen in aphids permit us to investigate the relative importance and potential interaction of maternal and current environments on phenotype. Although past studies have identified an influence of maternal host plant on offspring phenotype and reproduction in aphids, few have demonstrated the potential for these maternal effects to also interact with the aphid's current environment. By rearing multiple generations ofAphis nerii(Fonscolombe) (Hemiptera: Aphididae) on their host common milkweed,Asclepias syriaca(L.) (Apocynaceae), we tested the relative influence and interaction of both maternal and current environmental effects of crowding and plant quality on aphid body size and reproduction. Our results indicate that aphid body size increased with current plant quality and decreased with aphid density in both generations, with an additional direct, positive relationship between body size and fecundity. We did not find evidence for adaptive maternal effects, e.g., production of fewer, larger, offspring by stressed mothers. Instead, poor maternal environments constrained aphid body size and reproduction. Importantly, these adverse maternal effects were only seen in offspring where subsequent nymph population growth was allowed to increase unchecked, likely reducing available resources. Our study thus demonstrates that the significance of maternal effects in aphid development and reproduction can depend on current resource availability, shaping the phenotype and fecundity of offspring under stressful conditions. Incorporating this framework for how aphid body size and reproduction respond to current and maternal environments may improve predictions for how aphid population growth is impacted by resource limitation across generations.

Does maternal exposure to nicotine affect the oocyte quality and reproductive capacity in adult offspring?

Gonadal development begins in the intrauterine phase and females from most species are born with an established oocyte reserve. Exposure to drugs during gestation can compromise the offspring health, also affecting the gametes quality. Nicotine, the main component of cigarettes, is an oxidant agent capable of altering the fertility in men and women. As female gametes are susceptible to oxidative stress, this drug can damage the oolemma and affect oocyte maturation, induce errors during chromosomal segregation and DNA fragmentation. Oocyte mitochondria are particularly susceptible to injuries, contributing to the oocyte quality loss and embryonic development disruption. Thus, considering the high number of women who smoke during pregnancy, while significant events are occurring in the embryo for future fertility of offspring, we seek to verify the quality of the oocytes from adult rats exposed to nicotine during intrauterine phase and breastfeeding. Pregnant Wistar rats received nicotine by osmotic mini-pumps and the female progenies were evaluated in adulthood for oocyte quality (viability, lipid peroxidation, generation of reactive oxygen species and mitochondrial integrity) and reproductive capacity. Embryos (3dpc) and fetuses (20dpc) generated by these rats were also evaluated. The results showed that the dose of 2 mg/kg/day of nicotine through placenta and breast milk does not affect the number of oocytes and the fertility capacity of adult rats. However, it causes some morphological alterations in oocytes, mitochondrial changes, embryonic fragmentation and disruption of fetal development. The malformations in fetuses generated from these gametes can also indicate the occurrence of epigenetic modifications.

Developmental programming and ageing of male reproductive function.

Developmental programming predisposes offspring to metabolic, behavioural and reproductive dysfunction in adult life. Evidence is accumulating that ageing phenotype and longevity are in part developmentally programmed in each individual. Unfortunately, there are few studies addressing the effects of developmental programming by maternal nutrition on the rate of ageing of the male reproductive system. This review will discuss effects of foetal exposure to maternal environmental challenges on male offspring fertility and normal ageing of the male reproductive system. We focus on several key factors involved in reproductive ageing such as decreased hormone production, DNA fragmentation, oxidative stress, telomere shortening, epigenetics, maternal lifestyle and nutrition. There is compelling evidence that ageing of the male reproductive system is developmentally programmed. Both maternal over- or undernutrition accelerate ageing of male offspring reproductive function through similar mechanisms such as decreased serum testosterone levels, increase in oxidative stress biomarkers in both the testes and sperm and changes in sperm quality. Importantly, even in adult life, exercise in male offspring of obese mothers improves adverse effects of programming on reproductive function. Maternal consumption of a low-protein diet causes transgenerational effects in progeny via the paternal line. The seminal fluid has effects on the intrauterine environment. Programming by male factors may involve more than just the sperm. Improving knowledge on developmental programming ageing interactions will improve not only male health and life span but also the health of future generations by reducing programming via the paternal line.

Reproductive and embryological toxicity of lead acetate in male mice and their offspring and mitigation effects of quercetin

Exposure to heavy metals not only impacts on fertility in males, it may also affect the offspring. The aim of the present study was to examine the toxic effects of lead acetate on fertility in male mice and their offspring, and the potential effect of quercetin on mitigating the likely effects. Experimental mice were randomly divided into three groups and administered with (i) distilled water (control); (ii) lead acetate (150 mg/kg BW/day); (iii) lead acetate (150 mg/kg BW/day) with quercetin (75 mg/kg BW/day). Lead acetate administration in male mice adversely affected their fertility through changes in sperm motility, viability, morphology, maturity, membrane integrity, and intracellular reactive oxygen species (P < 0.05). Similar findings were observed in the offspring of the lead-treated male mice. Early embryonic development and implantation rate were also adversely influenced in both the sires and offspring when male mice were treated with lead acetate (P < 0.05). The data demonstrated that down-regulation of Cks2 (CDC28 protein kinase regulatory subunit-2) in sperm had an association with early embryonic development in lead acetate treated group. In conclusion, lead acetate administration adversely impacted on the fertility of the male mice and their male offspring fertility; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on male mice and their offspring.

Human total fertility rate affected by ambient temperatures in both the present and previous generations.

Elevated temperatures negatively affect human reproduction through several processes that regulate nutrient uptake and resource allocation in pregnant women. These can interfere with foetal development, resulting in low birth weight neonates with altered development trajectories. Temperatures that affect the current generation could, therefore, also have an impact on the following generation. We asked whether heat stress affected offspring fertility by asking if current and past ambient temperatures influenced total fertility rates (TFR) in human populations distributed across the world. We analysed time series data in 65 countries using simple regression analyses based on maximum temperatures and temperature amplitudes over 55 years. Supplemental longer time series (up to 100 years) provided information on response patterns in Northern Europe and Greenland's colder climates. There were clear and strong effects of temperatures on the TFR in the concurrent and the previous generation. Our temperature-based models account for 71-95% of the variation in TRF in European countries and Greenland, and 56-99% of the variation in 65 countries worldwide. Our findings are consistent with studies of seasonal variation in fertility and suggest that increased temperatures will negatively influence populations subjected to monthly maximum temperatures above 15-20 °C, while fertility in colder climates benefits from elevated temperatures. Our results provide strong evidence that ambient temperatures have important effects on human fertility, and that these effects persist into the following generation.

Evolutionary consequences of environmental effects on gamete performance.

Variation in pre- and post-release gamete environments can influence evolutionary processes by altering fertilization outcomes and offspring traits. It is now widely accepted that offspring inherit epigenetic information from both their mothers and fathers. Genetic and epigenetic alterations to eggs and sperm-acquired post-release may also persist post-fertilization with consequences for offspring developmental success and later-life fitness. In externally fertilizing species, gametes are directly exposed to anthropogenically induced environmental impacts including pollution, ocean acidification and climate change. When fertilization occurs within the female reproductive tract, although gametes are at least partially protected from external environmental variation, the selective environment is likely to vary among females. In both scenarios, gamete traits and selection on gametes can be influenced by environmental conditions such as temperature and pollution as well as intrinsic factors such as male and female reproductive fluids, which may be altered by changes in male and female health and physiology. Here, we highlight some of the pathways through which changes in gamete environments can affect fertilization dynamics, gamete interactions and ultimately offspring fitness. We hope that by drawing attention to this important yet often overlooked source of variation, we will inspire future research into the evolutionary implications of anthropogenic interference of gamete environments including the use of assisted reproductive technologies. This article is part of the theme issue 'How does epigenetics influence the course of evolution?'

Study on the effect of maternal administration of oxaliplatin on offspring testes using unbiased design-based stereology

Oxaliplatin (Ox) is widely used for the treatment of various tumors. Since Ox prevents DNA replication and transcription, it may affect organs with rapid cell divisions such as the testes. Although its use during pregnancy has been reported, no information regarding its effects on the testes of the offspring is not available yet. Thirty-two mice were randomly divided into four groups. The control group (1) was administered intraperitoneally 0.2 ml of saline three times a week for the 21 days of pre-pregnancy, pregnancy and lactation. Experimental groups 2, 3 and 4 received 3 mg/kg of oxaliplatin three times a week for 21 days during pre-pregnancy, pregnancy and lactation, respectively. The left testis was removed from male offspring 30 and 60 days after birth. The volume of the testes, seminiferous tubules and interstitial tissue, the surface area and height of the seminiferous epithelium, as well as the length and diameter of seminiferous tubules, were analyzed by means of stereology. Results showed a decrease in the evaluated parameters in experimental groups, in comparison with the control group. Due to the ameliorating effect of Ox on offspring testes, cautiousness is needed during maternal administration in order to preserve the fertility of male offspring.

Mates Matter: Gametophyte Kinship Recognition and Inbreeding in the Giant Kelp, Macrocystis pyrifera (Laminariales, Phaeophyceae).

Inbreeding, the mating between genetically related individuals, often results in reduced survival and fecundity of offspring, relative to outcrossing. Yet, high inbreeding rates are commonly observed in seaweeds, suggesting compensatory reproductive traits may affect the costs and benefits of the mating system. We experimentally manipulated inbreeding levels in controlled crossing experiments, using gametophytes from 19 populations ofMacrocystis pyriferaalong its Eastern Pacific coastal distribution (EPC). The objective was to investigate the effects of male-female kinship on female fecundity and fertility, to estimate inbreeding depression in the F1 progeny, and to assess the variability of these effects among different regions and habitats of the EPC. Results revealed that the presence and kinship of males had a significant effect on fecundity and fertility of female gametophytes. Females left alone or in the presence of sibling males express the highest gametophyte size, number, and size of oogonia, suggesting they were able to sense the presence and the identity of their mates before gamete contact. The opposite trend was observed for the production of embryos per female gametes, indicating higher costs of selfing and parthenogenesis than outcrossing on fertility. However, the increased fecundity compensated for the reduced fertility, leading to a stable overall reproductive output. Inbreeding also affected morphological traits of juvenile sporophytes, but not their heatwave tolerance. The male-female kinship effect was stronger in high-latitude populations, suggesting that females from low-latitude marginal populations might have evolved to mate with any male gamete to guarantee reproductive success.