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In Brief
Unconventional oil and natural gas (UOG) operations, particularly hydraulic fracturing, have revolutionized oil and gas production, using and containing complex mixtures of chemicals that may impact reproductive health. While there is growing evidence for effects on births in hydraulic fracturing/UOG regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about these practices and reproductive health.
Abstract
Unconventional oil and natural gas (UOG) operations have emerged over the last four decades to transform oil and gas production in the United States and globally by unlocking previously inaccessible hydrocarbon deposits. UOG development utilizes many compounds associated with conventional oil and gas, as well as some specific to UOG extraction, particularly during hydraulic fracturing (HF). While research is increasing on UOG chemicals and their mixtures, this review discusses the current evidence for reproductive toxicity following exposures to UOG/HF mixtures. These complex chemical mixtures have been demonstrated to interact with numerous mechanisms known to influence reproductive health. A growing number of environmental and controlled laboratory testing studies have reported adverse reproductive health effects in animals exposed to various UOG chemical mixtures. An expanding body of epidemiological literature has assessed adverse birth outcomes, although none has directly examined reproductive measures such as time to pregnancy, semen quality, and other direct measures of fertility. The existing literature provides moderate evidence for decreased birth weights, increased risk of small for gestational age and/or preterm birth, increased congenital abnormalities, and increased infant mortality, though importantly, studies are widely variable in methods used. Most studies utilized distance from UOG operations as an exposure proxy and did not measure actual chemical exposures experienced by those living near these operations. As such, while there is growing evidence for effects on births in these regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about UOG development and reproductive health.
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Centre for Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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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.
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In brief
PLCZ1 mutations are related to total fertilisation failure (TFF) after intracytoplasmic sperm injection (ICSI), characterised by abnormal oocyte oscillations. The novel PLCZ1 compound heterozygous mutations reported by this study were associated with TFF after ICSI, with one of the mutations indicating a gene dosage effect.
Abstract
Oocyte activation failure is thought to be one of the main factors for total fertilisation failure (TFF) after intracytoplasmic sperm injection (ICSI), which could be induced by abnormal calcium oscillations. Phospholipase C zeta (PLCZ), a sperm factor, is associated with Ca2+ oscillations in mammalian oocytes. To date, some mutations in PLCZ1 (the gene that encodes PLCZ) have been linked to TFF, as demonstrated by the observed reduction in protein levels or activity to induce Ca2+ oscillations. In this study, normozoospermic males whose sperms exhibited TFF after ICSI and their families were recruited. First, mutations in the PLCZ1 sequence were identified by whole exome sequencing and validated using Sanger sequencing. Then, the locations of PLCZ1/PLCZ and the transcript and protein levels in the sperm of the patients were studied. Subsequently, in vitro function analysis and in silico analysis were performed to investigate the function–structure correlation of mutations identified in PLCZ1 using western blotting, immunofluorescence, RT-qPCR, and molecular simulation. Ca2+ oscillations were detected after cRNA microinjection into MII mouse oocytes to investigate calcium oscillations induced by abnormal PLCZ. Five variants with compound heterozygosity were identified, consisting of five new mutations and three previously reported mutations distributed across the main domains of PLCZ, except the EF hands domain. The transcript and protein levels decreased to varying degrees among all detected mutations in PLCZ1 when transfected in HEK293T cells. Among these, mutations in M138V and R391* of PLCZ were unable to trigger typical Ca2+ oscillations. In case 5, aberrant localisation of PLCZ in the sperm head and an increased expression of PLCZ in the sperm were observed. In conclusion, this study enhances the potential for genetic diagnosis of TFF in clinics and elucidates the possible relationship between the function and structure of PLCZ in novel mutations.
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Sexual reproduction—from both physiological and behavioral perspectives—is dependent upon appropriate connections between a diverse, hormone-modulated network of neural regions. Importantly, these substrates are regulated by hormones across the lifespan from early development to adulthood, making them targets of endocrine-disrupting chemicals (EDCs). Rodents, such as mice and rats, are invaluable to the characterization of EDCs because of their sex-specific, stereotyped appetitive and consummatory reproductive behaviors. Phthalates, bisphenol A (BPA), and EDC mixtures pose a salient risk to the health of humans, wildlife, and livestock because these synthetic compounds are ubiquitous due to their widespread use in mass production of consumer and industrial goods. This review outlines how the hypothalamic-pituitary-gonadal axis regulates male and female sexual behaviors, and how phthalates and BPA can perturb appetitive and consummatory behaviors and impact neural substrates that modulate reproductive behavior. We will then discuss how to progress toward a clearer understanding of the reproductive and neurobiological changes that occur due to EDC exposure.
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In brief
Since available therapeutic approaches for chemotherapy-induced non-obstructive azoospermia (NOA) patients are not enough efficient, an urgent need for treatment alternatives is felt. This study shows that adipose tissue-derived mesenchymal stem cells-derived exosome (AD-Exo) treatment is more effective in ameliorating busulfan-induced NOA rat models compared to platelet-rich plasma (PRP).
Abstract
Patients with non-obstructive azoospermia (NOA) are unable to have their children. Therefore, there is an urgent need for additional treatment alternatives for these patients. Recently, novel treatments based on the exosomes derived from mesenchymal stem cells (MSCs) as the agents responsible for exerting the paracrine effects and consequently biological functions of MSCs are proposed. Besides, platelet-rich plasma (PRP) as a significant blood byproduct has been therapeutically applied in several male infertility studies. In this study, we compared the effects of PRP and exosome treatment on spermatogenesis restoration in NOA rat models. Exosomes and PRP were isolated from the adipose tissue-derived MSCs (AD-MSCs) collected from conditioned medium and peripheral blood of human volunteers, respectively. Non-obstructive azoospermia (NOA) induction was done through two doses of busulfan at a 21-day interval. Thirty-five days after NOA induction, intratesticular injection of AD-MSCs-derived exosome (AD-Exo), PRP, and PBS was performed. The control group did not receive any treatment. Two months later, the rats were euthanized for further analysis. Our results revealed that both AD-Exo and PRP treatments improved the size and weight of testis, modulated the expression level of Dazl, Ddx4, Stra8, Pwil1, and Ccna1, and ameliorated the serum level of LDH, SOD, and GR enzymes in NOA rats. Moreover, the AD-Exo group showed improved testosterone, GPx, MAD, and CAT serum levels, sperm motility, and protein levels of DAZL and DDX4. This investigation verified the more efficient effects of AD-Exo treatment in comparison to PRP in ameliorating busulfan-induced NOA rat models.
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In brief
Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos.
Abstract
Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.
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In rodents, male-derived pheromones play fundamental roles in reproduction. The Hirosaki hairless rat (HHR) is a mutant strain derived from the Sprague–Dawley rat (SDR). While investigating the natural mating between single males and females, (SDR♂ x SDR♀) or (HHR♂ x HHR♀), the HHRs showed higher fecundity than the SDRs; the mean period between mating and delivery was shorter and every HHR pair gave birth, whereas approximately half of the SDR pairs gave birth in the 3 months of experimental testing. By changing partners between the HHRs and SDRs, (SDR♂ x HHR♀) or (HHR♂ x SDR♀), we attributed the fecundity difference to males. However, no significant difference was observed in the litter size, the concentration, morphology, or motility of sperm in the cauda epididymis, or the testosterone concentration in the serum between the SDR and HHR males. When an SDR and HHR male were simultaneously mated with a single female, the HHR males always succeeded in leaving progeny. Therefore, we assumed that the reason for the fecundity difference was the difference in copulation efficiency and focused on male-derived pheromones that may induce reproductive behaviors in females. Whereas Darcin (MUP20), one of the pheromones produced in the liver, did not appear to be involved, the extraorbital lacrimal gland (ELG) was heavier in the HHR males and showed larger amounts of pheromones, namely exocrine gland-secreting peptide 1 (ESP1) and cystatin-related protein 1 (CRP1). These results suggest that the fecundity difference is due to the difference in amounts of ELG-derived pheromones.
Metabolomics and Proteomics Technology Platform, West China Hospital, Sichuan University, Chengdu, PR China
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In brief
The metabolic processes of the gestation period in pandas remain poorly understood. Our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.
Abstract
There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.
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Transgender individuals who pursue alignment with their gender identity, through medical treatments or surgery face challenges to family building because the medical community lacks the understanding or infrastructure to serve the reproductive needs of transgender or non-binary people. Fertility preservation (FP) offers a crucial opportunity for the transgender community, enabling individuals to exercise autonomy over their reproductive choices. While fertility preservation has been extensively studied in other populations such as cancer patients, the unique biology and clinical care of the transgender and gender non-binarydiverse (TGD) individuals has challenged direct translation of what can be offered for cisgender individuals. Additionally, the FP services in transgender communities are reportedly under-utilized, despite the prevalent desire of TGD individuals to have children. This review aims to provide up-to-date information on the current standard of care and experimental FP options available to TGD individuals and their potential reproductive outcomes. We will also discuss the barriers to the success of FP utilization, from both the biology/medical aspect and the perspectives of TGD population. By recognizing the unique family building challenges faced by TGD people and potential areas of improvement, appropriate adjustments can be made to better support fertility preservation in the TGD community.
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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This work describes a valuable and reproducible method for generating optically clear bovine ovary-derived hydrogels that support in vitro murine follicle growth. These techniques are the foundation in which follicle growth dynamics and matrisome protein composition may be correlated to reveal the influence of matrisome proteins on folliculogenesis.
