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Lay summary

The World Health Organization (WHO) has recognized that oxidative stress may have a role in male infertility. Oxidative stress happens when there is an imbalance between the production of molecules containing oxygen and the antioxidants, molecules that neutralize the molecules containing oxygen. The molecules containing oxygen can cause damage to sperm DNA. This damage can be measured using a particular index and this study looked at whether the concentration of the sperm sample might have an impact on results and suggests this should be taken into consideration by clinicians and researchers.

Lay summary

The relationship between race/ethnicity and endometriosis has been explored for over a century. Historical bias and poorly conducted research have led to the idea that this condition is less likely to be diagnosed in certain racial groups, such as Black women. We review the current state of evidence and highlight important limitations within medical education and research on this topic. Finally, we advocate for a shifting viewpoint as we strive to deliver equitable and outstanding care for all endometriosis patients.

Graphical abstract

Abstract

Recurrent reproductive failure (RRF) encompasses recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). These highly prevalent, distressing conditions have many unanswered questions regarding aetiology and management. Oestrogen receptor beta (ERβ) is the predominant oestrogen receptor expressed in the vascular endothelium of the endometrium during the window of implantation (WOI). The establishment of normal endometrial receptivity is integrally associated with progesterone receptor (PR). Therefore, we aimed to investigate whether women with RRF have clinical, type-specific endometrial aberrations of ERβ, PR and Ki-67 expression during the WOI. Thirty-eight endometrial biopsies were collected; 29 RRF (10 RIF, 9 recurrent loss of early pregnancy (RLEP) and 10 recurrent fetal loss (RFL)) and 9 fertile controls (FC). Within RIF, RLEP and RFL groups, the perivascular compartment showed significantly lower levels of ERβ vs FC (P  = 0.02, P  = 0.03 and P  = 0.01, respectively). Vascular endothelium also displayed significantly lower levels of ERβ within RIF and RFL cohorts vs FC (P  = 0.03 and P  = 0.003). The expression of Ki-67 was significantly lower within vascular endothelium of all RRF; RIF (P  = 0.02), RLEP (P  = 0.02) and RFL (P  <0.01). PR was significantly reduced (P  <0.001) in the perivascular area of women with RIF. These findings provide novel insights into biological correlates of clinical subtypes of RRF. The endometrium of women with RRF display significantly altered levels of ERβ, PR and Ki-67 during the WOI, furthering our understanding of the defective endometrial phenotype of women suffering from RRF, with possible impaired glandular function, angiogenesis and decidualisation.

Lay summary

Recurrent reproductive failure (RRF) refers to a group of devastating conditions with many unanswered questions regarding their causes and treatment options. The lining of the womb, the endometrium, is primed and suitable for successful embryo implantation for a short time during the menstrual cycle; the window of implantation (WOI). Oestrogen is a key hormone that plays an important role in regulating the endometrium and its effects are exerted via two oestrogen receptor subtypes. Oestrogen receptor beta (ERβ) is the main oestrogen receptor present during the WOI. Progesterone receptor allows the other main hormone, progesterone, to influence the endometrial activity and Ki-67 reflects the proliferative activity of the cells within the endometrium. We investigated the expression of these markers in endometrial samples collected from women with RRF and proven fertility. We found that the endometrium of women with RRF has significantly lower levels of ERβ and Ki-67 during the WOI, possibly leading to unsuccessful pregnancies.

Lay summary

In recent decades, testicular cancer rates have quadrupled in young men while sperm counts have dropped by half. Both conditions may be related to exposure of fetuses or infants to noxious substances causing disruption of normal testis development. To study the effects of any putative factor on testis development, we established an animal model of testis tissue regeneration. We collected newborn piglet testes after routine castration, used enzymes to completely dissociate testis cells, exposed the cells to two key growth factors (EGF or GDNF), and implanted the cells under the back skin of recipient mice, acting as live incubators. We then examined implant samples after 1, 2, 4, or 8 weeks and assessed testis regeneration. Overall, the high dose of each growth factor had adverse effects on the formation of normal testis. Therefore, this novel implantation model may also be used to study the effects of potentially harmful substances on testis development.

Lay summary

This paper discusses the role that lipids play in the very early stages of pregnancy in the mare. Lipids are microscopic non-soluble molecules that are important components of living cells. The manuscript discusses how lipids influence the reproductive cycle of mares, including ovulation and the detailed biological process of becoming pregnant. It explains how lipids are identified in a laboratory setting with a newly developing technology known as ‘lipodomics’. The technology may lead to a more detailed understanding of how mares become pregnant. The focus of the paper is on mare reproduction, but it also draws on similarities with reproduction in other mammals. Remarkably there are gaps in much of our knowledge about the finer details of pregnancy in the horse, and the paper summarises what we already know about lipids, highlighting areas for further research.

Objective

To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions.

Methods

A systematic review and meta-analysis aiming to evaluate the spermicidal activity of N-9 on motility, was conducted in PubMed, EMBASE, and Cochrane databases by 10 March 2021. The counted numbers of progressive motile (PR) sperm in cervical mucus and the vanguard sperm penetration distances were analyzed. Other effects on sperm structures and physiological activities were reviewed as well.

Results

In the pooled results, percentages or counted numbers of PR sperm decreased after the treatment of N-9. Vanguard sperm penetration distance was shortened in treated groups. N-9 has been confirmed to damage the structures of sperm, as well as other organelles like acrosome and mitochondria. The physiological activities such as generation of reactive oxygen species, superoxide dismutase activity, acrosin activity, and hemizona binding were all inhibited in the reviewed studies.

Conclusions

N-9 has several impacts on sperm owing to its potency in reducing sperm motility and cervical mucus penetration, as well as other functional competencies.

Lay summary

Nonoxynol-9 (N-9) has been used worldwide as a spermicide to kill sperm for more than 60 years but can cause side effects including vaginal irritation and can increase the rate of contraceptive failure. A detailed analysis of published literature aiming to evaluate the spermicidal activity of N-9 on sperm was carried out. In the pooled results, N-9 reduced the number of active sperm and the distance they traveled. It also caused damage to the structures of sperm and to the way the sperm acted and interacted with the egg. In conclusion, N-9 impacts on sperm in a number of ways that lead to sperm death and dysfunction.

Lay summary

Fertility preservation is a rapidly advancing field with numerous broad applications ranging from retaining the prospect of fertility in a child with cancer to protecting an entire species from extinction. In recent years, huge strides have been made in understanding the biology of male and female reproduction in animals and humans and using this knowledge to develop strategies for fertility preservation across a range of clinical and ecological applications. This Reproduction and Fertility preservation series is composed of articles from experts on this topic and these will highlight key developments in fertility preservation and also identify the challenges that still face this exciting and relatively new field.

Lay summary

Critical moments occur at different stages of placental formation in pigs, where the expression of angiogenic factors, that is, molecules that stimulate the formation of blood vessels must be adequate to promote their development. This exchange is necessary to cover the increasing nutritional demands of fetuses in continuous development. Determining the changes in the area of capillary density in relation to fetal development and the expression of angiogenic factors throughout pregnancy in pigs could contribute to understanding the causes of fetal loss. Placental samples were obtained at gestational days 40, 77, 85 and 114 (n = 7, 10, 7 and 5, respectively). We found that the capillary area density increases accompanying fetal growth with advancing gestation and an increase in capillary area density in late-middle gestation, around day 77, is due to the expansion in the number of small blood vessels on the maternal side. The present findings suggest that an intense angiogenesis would be present even until late-middle gestation at day 77 of pregnancy, with the predominance of angiogenic stimulation by specific molecules that promote this process.

Lay summary

Heavy periods are common and debilitating, but we do not fully understand how they are caused. Increased understanding of menstrual bleeding could result in new treatments for problematic periods. Low oxygen levels are present in the womb lining during a period. These low oxygen levels help trigger the repair process required to stop menstrual bleeding. MicroRNAs (miRNAs) are small molecules that can affect cell function, and some are regulated by oxygen levels. We examined whether such miRNAs were present in the womb lining during a period. To overcome the variability present in humans, we studied the womb of mice given hormones to mimic the human menstrual cycle. We revealed that two miRNAs known to be regulated by oxygen levels were increased in the womb during menstruation. These miRNAs may help regulate menstrual blood loss and merit further study as a potential target for future treatments for heavy periods.

Graphical abstract

A mouse model to study uterine specific contributions to pregnancy.

Maternal environmental exposures can exert impacts on the ability of the uterus to sustain healthy pregnancy. To establish an in vivo model to study this, we designed an ovariectomized mouse embryo transfer model. The rationale being future studies could expose recipient female mice to variables such as altered diet, drug, temperature, air, or activity exposure among others to define their impacts on the uterine contribution to pregnancy. Ovariectomy ensures the extent of the variable is limited to exploring outcomes on uterine but not ovarian function. Embryo transfer from healthy, unexposed donor mice guarantees that any impacts of the variable are attributed to the maternal uterine but not the embryonic state. Pregnancy outcomes including pregnancy success (number of implantation sites) and viability (number of viable vs resorbing implantation sites) can be investigated. Numerous functional outcomes can be assessed, including developmental competence encompassing decidual, placental, fetal, and vascular morphology and/or function (e.g. measured using Doppler ultrasound, comparisons of fetal growth, or molecular or histological characterization of the decidua, placenta, and fetal tissues).

Lay summary

Many pregnancy complications occur because of problems in the womb (uterus), specifically the womb lining. There is a close relationship between the hormone function of the ovaries and the uterus and distinguishing between the way they both impact pregnancy success is difficult in existing studies using animals. Here, we developed a new animal model to utilize in addressing these gaps in our understanding of pregnancy.