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Altered gut microbiota (dysbiosis), inflammation and weight gain are pivotal to the success of normal pregnancy. These are features of metabolic syndrome that ordinarily increase the risk of type 2 diabetes in non-pregnant individuals. Though gut microbiota influences host energy metabolism and homeostasis, the outcome (healthy or unhealthy) varies depending on pregnancy status. In a healthy pregnancy, the gut microbiota is altered to promote metabolic and immunological changes beneficial to the mother and foetus but could connote a disease state in non-pregnant individuals. During the later stages of gestation, metabolic syndrome-like features, that is, obesity-related gut dysbiotic microbiota, increased insulin resistance, and elevated pro-inflammatory cytokines, promote energy storage in adipose tissue for rapid foetal growth and development, and in preparation for energy-consuming processes such as parturition and lactation. The origin of this gestation-associated host–microbial interaction is still elusive. Therefore, this review critically examined the host–microbial interactions in the gastrointestinal tract of pregnant women at late gestation (third trimester) that shift host metabolism in favour of a diabetogenic or metabolic syndrome-like phenotype. Whether the diabetogenic effects of such interactions are indeed beneficial to both mother and foetus was also discussed with plausible mechanistic pathways and associations highlighted.
Lay summary
In non-pregnant women, increased blood glucose, fat accumulation, and prolonged immune response lead to obesity and diabetes. However, during the later stages of pregnancy, the changes in the body’s metabolism described previously do not lead to disease, instead pregnancy facilitates the storage of sufficient energy in fat cells for rapid growth and development of the foetus. The excess energy stores also prepares the mother for labour and breastfeeding. This review examines the role of the normal bacteria in the digestive tract in this beneficial energy accumulation and transfer between the mother and foetus without leading to obesity, diabetes and hypertension in pregnancy.
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Lay summary
Health-promoting bacteria (lactobacilli) exist in harmony with the vaginal environment. They are the predominant vaginal bacterial species during pregnancy. However, the possibility of infection and inappropriate immune response are linked with unprompted preterm delivery (PTD). Other invasive lactobacilli can alter the chemical environment of the vagina as they seek to promote their growth. This study measured the change in concentration of biochemical compounds and predominant bacterial species in vaginal fluid that are linked to PTD. The study recruited 300 healthy pregnant women who provided vaginal fluid samples during the second trimester. The women who harboured more of Lactobacillus jensenii over Lactobacillus crispatus (both reported as health-promoting bacteria) in their vaginal fluid had less lactate and glutamate and experienced more PTD. This suggests that lactate and glutamate levels in vaginal fluid may have clinical application in identifying which Lactobacillus species is most active. These chemical biomarkers could provide quick and accurate prediction of PTD risk in clinical settings.
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Graphical abstract
Abstract
The phenomenal extracellular matrix (ECM) remodelling of the cervix that precedes the myometrial contraction of labour at term or preterm appears to share some common mechanisms with the occurrence, growth, invasion and metastasis of cervical carcinoma. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are pivotal to the complex extracellular tissue modulation that includes degradation, remodelling and exchange of ECM components, which contribute to homeostasis under normal physiological conditions such as cervical remodelling during pregnancy and puerperium. However, in cancer such as that of the uterine cervix, this extensive network of extracellular tissue modulation is altered leading to disrupted cell–cell and cell–basement membrane adhesion, abnormal tissue growth, neovascularization and metastasis that disrupt homeostasis. Cervical ECM remodelling during pregnancy and puerperium could be a physiological albeit benign neoplasm. In this review, we examined the pathophysiologic differences and similarities in the role of MMPs in cervical remodelling and cervical carcinoma.
Lay summary
During pregnancy and childbirth, the cervix, which is the barrel-shaped lower portion of the womb that connects to the vagina, gradually softens, shortens and opens to allow birth of the baby. This process requires structural and biochemical changes in the cervix that are stimulated by enzymes known as matrix metalloproteinases. Interestingly, these enzymes also affect the structural and biochemical framework of the cervix during cervical cancer, although cervical cancers usually occur after infection by human papillomavirus. This review is intended to identify and explain the similarities and differences between the structural and chemical changes in the cervix during pregnancy and childbirth and the changes seen in cervical cancer.
Department of Medical Biotechnology, National Biotechnology Development Agency, Abuja, Nigeria
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Sickle cell disease (SCD) poses an increased risk of infertility, pregnancy complications and maternal and perinatal mortality among women of reproductive age. This risk is particularly higher for women in sub-Saharan Africa, where the disease burden is highest and access to comprehensive health care is limited, as well as in other countries with a high SCD prevalence due to migration. Disease-modifying treatments for SCD could directly and indirectly harm the ovaries, potentially compromising the quality and quantity of existing oocytes. Therefore, it is essential to explore alternative interventions, such as nutritional modifications that are less harmful and cost-effective in order to improve reproductive outcomes and enhance the overall well-being of both mother and child in this population. Maintaining optimal levels of B12 may possibly provide benefits to the ovaries and pregnancy by decreasing homocysteine levels, increasing nitric oxide (NO) bioavailability and promoting antioxidant and anti-inflammatory activities. Individuals living with SCD are more susceptible to vitamin B12 (B12) deficiency. However, there is a lack of clinical data investigating the relationship between systemic levels of B12, its supplementation, and reproductive outcome measures in SCD women. Therefore, this review aims to examine the current evidence regarding the impact of SCD on female reproductive health and the role of B12 in the reproductive biology of women living with SCD.
Lay summary
Poor reproductive health is a concern for patients with sickle cell disease (SCD). SCD can lead to damage to the ovaries. Most of the therapies for sickle cell disease are toxic to the ovaries, expensive and unavailable to affected women, particularly those living in resource-poor areas such as sub-Saharan Africa. There is a need to seek less harmful and affordable interventions such as nutrition to improve reproductive outcomes for women with SCD who are of child-bearing age. Good levels of vitamin B12 have been found to maintain ovarian health and pregnancy. Patients with SCD have been reported to have a high risk of vitamin B12 deficiency, but the impact of B12 on reproduction in this group of women is yet to be evaluated. The review explores current evidence of the impact of both SCD and B12 on female reproduction.
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Lay summary
The need to develop new treatments to prevent unprompted premature delivery before 37 weeks of pregnancy remains pressing and unmet. Bacteria (Lactobacillus species) that promote vaginal health produce biochemical compounds that prevent the growth of microbes such as Gardnerella vaginalis. Overgrowth of G. vaginalis can cause vaginal infection with smelly discharge and increase a woman’s risk of sexually transmitted infections and premature delivery. In this study, we examined how normal health-promoting (L. crispatus) and potentially harmful (G. vaginalis) vaginal bacteria interact in a laboratory setting. This was in order to observe natural and effective agent(s) from L. crispatus that can hinder the growth of G. vaginalis and accompanying immune response. We observed that L. crispatus clears G. vaginalis by itself and with several biochemical compounds that it produces. Such biochemical compounds can be developed into treatment for vaginal infections and premature delivery due to infection and inappropriate immune response.
