Effects of female obesity on conception, pregnancy and the health of offspring.

Overweight and obesity are defined as abnormal or excessive fat accumulation that can damage health. The World Health Organization (WHO) recommends use of BMI to classify overweight and obesity in adults. BMI is defined as weight in kilograms divided by height in meters squared (kg/m 2 ). Adults with a BMI of ≥ 25 are regarded as overweight, whereas those with a BMI of ≥ 30 as obese ( 1 ). In recent decades, the incidence of obesity has risen at an alarming rate worldwide, and is reaching epidemic levels. In 2015, an estimated 1.9 billion and 609 million adults were respectively suffering from overweight and obese globally, accounting for about 39% of the world’s population, and generally women have higher rates of obesity than men ( 2 ). Studies have shown that obesity increases the risk of many chronic disorders, including cardiovascular disease, hypertension, diabetes and even several cancer types (e.g. colon, breast, endometrium cancers) ( 3 ). In addition, a growing body of research has revealed that obese women are at a high risk for reproductive health. Their disturbed reproductive health status tend to associate with poor fertilization, abnormal embryo development, poor offspring growth and vulnerability to disease ( 4 – 6 ). Thus, in present study, we provide an overview for current knowledge of the effect of obesity on fertility, pregnancy outcome and health status of offspring.

Based on the above, losing weight is important to reduce the risk of obesity-related reproductive dysfunction. In a clinical study involving 170 women undergoing in vitro fertilization, women with short-term weight loss have significantly higher production of mid-stage II oocytes than obese women ( 39 ). In obese women, reduced-calorie diet and exercise interventions are recognized as an effective way to lose weight, which is associated with improved ovulation and pregnancy rates for women. In a prospective study of 87 obese women, the subjects made changes in diet, exercise and lifestyle for 6 months. Finally, the women who completed the 6 months (total 67) lost an average of 10.2 kg/m 2 . Among them, 90% resumed spontaneous ovulation, 77.6% conceived (32.7% spontaneously), 67% achieved a live birth ( 40 ). Conversely, none of these changes occurred in the women who did not complete the treatment. Thus, weight loss can help to improve ovulation, pregnancy and live birth, and thus women with a high BMI should be advised to lose weight prior to conceiving.

An increasing number of experiments have demonstrated that maternal obesity increases the prevalence of future metabolic dysfunction and malformation in the offspring. Children of obese mothers are more likely to develop obesity, type 2 diabetes, kidney disease, hypertension and cardiovascular disease as adults ( 26 ). It was reported that maternal obesity increased risk of developing congenital kidney defects in the offspring by 22% ( 27 ). Moreover, the offspring of obese mothers had worse glomerular damage in comparison with offspring of normal-weight mothers ( 28 ). The mechanism of obesity-related nephropathy in offspring induced by maternal obesity is multifactorial. Lipid metabolism disorders have been reported to be associated with the occurrence of kidney disease ( 29 ). In the pathogenesis of chronic kidney injury, free fatty acids (FAs) and triglycerides could be freely filtered and reabsorbed by glomerular and tubulointerstitial cells ( 30 ). Free fatty acids functions as a link between adipose tissue activity and chronic inflammation, owing to their capability of promoting oxidative stress and inflammation ( 31 ). The excess lipid induces the production of reactive oxygen species, pro-fibrotic growth factors and pro-inflammatory cytokines, ultimately developing irreversible tubular damage and tubulointerstitial fibrosis ( 32 ). As expected, Yang et al. observed that the inflammation increases cellular uptake of fatty acids, finally triggering glomerular damage in animal experiments ( 33 ). Additionally, other metabolic risk factors also may underlie the obesity-related nephropathy such as hypertension, insulin resistance, and dyslipidemia. Epidemiological studies have revealed a general association between maternal obesity and risk for congenital heart defects in the offspring (e.g. septal defects, conotruncal defects, aortic arch defects). Congenital heart defects, the most common type of malformation, accounts for one-third of all severe malformation ( 34 ). There is plenty of evidence showing that increased fat mass is associated with insulin resistance, hyperinsulinemia, lipotoxicity and inflammation, which may adversely impact the embryo development ( 35 ). It has also been suggested that maternal obesity may impair the self-renewal in stem cells and induce epigenetic alteration in the embryo, contributing to cardiac malformations ( 36 ). Meanwhile, some reported that the offspring of obese women also have an increased risk of being obese. Likewise, increased leptin secretion by excessive adipose tissue leads to insulin resistance and inflammatory response, and thereby directly elicits adverse cardiovascular effects ( 37 ). In obese offspring, fatty tissue accumulation increases the stroke volume of the left ventricle, which places an additional burden on the heart. These changes would result in hypertrophy and enlargement of the ventricles, and even predispose patients to the development of heart failure ( 38 ).

In summary, obesity in women carries the risk of infertility and negative effects on the fetus and offspring. Fortunately, these adverse outcomes can be avoided by moderate weight loss. Meanwhile, for the health of more women, more in-depth research is needed to further understand the relationship between obesity and female reproduction.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This research is respectively supported by the National Natural Science Foundation of China (No.81973574, No.82174082, No.81860443), and the Natural Science Foundation of Guangxi (No.2019GXNSFFA245001). Scientific Research Promotion Project for Young and Middle-aged Faculty and Staff of Guilin Medical University ((No. 2018glmcy033).

JT and JC for research project with conception, organization, and execution. WW, XZ, BZ, and BG for statistical analysis with design, execution, review, and critique. JT and JC for manuscript preparation with writing of the first draft, review, and critique. All authors contributed to the article and approved the submitted version.