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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.

Lay summary

Human pregnancy lasts approximately 266 days. If a baby is born early, organs may be poorly formed but if pregnancy continues past this time, stillbirth risk is increased. Gestational duration is regulated by the placenta. As the placenta approaches the end of pregnancy, it displays properties similar to tissues from aged individuals. However, it is unknown how this placental ageing contributes to pregnancy duration. This study characterised normal placental ageing by measuring properties of mitochondria in healthy placentas collected at four different gestational ages ranging from 7 days before birth to 1 day before birth of the 19-day mouse pregnancy. We found that mitochondrial number increased per cell but that a marker of mitochondrial function was reduced. Proteins that control mitochondrial number, morphology and function also changed over time. This work lays the platform to understand how placental ageing contributes to adverse pregnancy outcomes related to altered pregnancy duration.

Lay summary

Q fever is a bacterial disease that passes between animals and humans and causes disease in both. The disease has been associated with pregnancy complications including miscarriage. This study was undertaken to identify if Q fever exposure was correlated with miscarriage in 369 women attending a pregnancy support unit in Edinburgh. The women in the study were in two groups, the miscarriage group with 251 women who had experienced a miscarriage and a control group of 118 women who had not experienced miscarriage. Three women were found to be positive for Q fever antibodies, suggesting that they had previously been exposed to the infection and all of them were from the group who had experienced miscarriage. The study indicates that Q fever is relatively rare in women attending an urban Scottish hospital suggesting that the infection is not a major cause of miscarriage in this population. However, as Q fever antibodies could only be found in women within the miscarriage group, it suggests that the infection cannot be ruled out as a potential cause of miscarriage in individual cases.

Lay summary

Cow fertility is important for efficient, profitable dairy farming. Cows that take too long after calving to become fertile are problematic. We tested a synthetically made, long-acting hormone called kisspeptin (Kp) to advance the time that cows become fertile after calving. Twenty-four dairy cows that had been calved for 3–4 weeks were used. One group of eight cows received an injection of Kp at the morning milking, another eight cows received Kp at both the morning and afternoon milking, while the last group of eight cows served as untreated controls. Kp treatment caused a desirable hormone response from the cows’ brain. Normal oestrous cycles resulted, but only when a mature follicle was present in the ovary. Further study is required to analyse whether the use of a long-acting Kp drug could be used as an effective treatment for stimulating dairy cows to become more fertile after calving.