Aquaporins—among them, AQP5—are responsible for transporting water across biological membranes, which is an important process in all living organisms. The transient receptor potential channel 4 (TRPV4) is a cation channel that is mostly calcium-permeable and can also be activated by osmotic stimuli. It plays a role in a number of different functions in the body, e.g., the development of bones and cartilage, and it is involved in the body’s osmoregulation, the generation of certain types of sensation (pain), and apoptosis. Our earlier studies on the uterus and the literature data aroused our interest in the physiological role of the cooperation of AQP5 and TRPV4. In this review, we focus on the co-expression and cooperation of AQP5 and TRPV4 in the lung, salivary glands, uterus, adipose tissues, and lens. Understanding the cooperation between AQP5 and TRPV4 may contribute to the development of new drug candidates and the therapy of several disorders (e.g., preterm birth, cataract, ischemia/reperfusion-induced edema, exercise- or cold-induced asthma).

Obesity affects approximately 30% of pregnancies worldwide and is one of the leading metabolic disorders among pregnant women. Maternal obesity is often associated with placental dysfunction and structural alterations, which increase the risk of developing complications. Efflux transporters, including P-glycoprotein (P-gp), may impact placental function and fetal development. Consequently, our research examined the effects of obesity on P-glycoprotein expression in both a rat model and human placental tissue. P-gp expression was measured by RT-PCR and Western blot techniques in human and rat placental tissues. Moreover, we further characterized the high-fat and high-sugar diet (HFHSD)-induced gestational obesity rat model by measuring tissue weights. Significant decreases were observed in fetal, placental, and uterus weights in the obese animals near the end of pregnancy. In obese rats, mRNA and protein expression of placental P-gp showed a reduction on gestation days 15, 20, and 22. A similar P-gp reduction was observed in the term placenta in obese women in mRNA and protein levels. We hypothesize that the reduced expression of P-gp may heighten the susceptibility of both the fetus and placenta to P-gp substrates. This alteration could potentially result in an increased risk of pregnancy complications and obesity-related drug contraindications linked to P-gp transport during pregnancy.

Aquaporins (AQPs) are expressed in the uterus, playing a physiological role during pregnancy. An osmotic pathway—through AQP5—may modify the transient potential vanilloid 4 (TRPV4) function and uterine contraction. Our aim was to determine the role of TRPV4 antagonist citral in the regulation of pregnant uterine contraction. In vitro uterine contractions were evoked by KCl and the response was modified with citral. The expressions of TRPV4 and AQP5 were measured by RT-PCR and Western blot techniques. The lengths of gestational periods were determined in normal and LPS-induced preterm births after citral treatment, in vivo. Citral significantly decreased the uterine contraction on day 22 of pregnancy. AQP5 expression significantly increased after citral incubation; however, TRPV4 expression did not show significant changes. After citral pretreatment, the gestational period was extended both in normal and LPS-induced preterm births. Our results suppose that the downregulation of AQP5 may initiate hypertonic stress, activating TRPV4 the uterine contraction on the last day of the gestational period. The putative cooperation between AQP5 and TRPV4 may open a novel target to treat or prevent preterm birth.

Objectives: Obesity and the associated metabolic dysfunction influence fertility performance at molecular levels and ABC transporters are considered as potential molecular factors affecting fertility both in the testis and sperm; therefore, we aimed to examine the effect of a short-term diet-induced obesity on testicular and spermatic ABC transporters in a rat model focusing on the expressions of P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (BCRP, Abcg2). The testicular androgen state involving aromatase enzyme (Cyp19a1), androgen receptor (Ar), and testosterone levels were also evaluated. Methods: Obesity was induced in male Sprague Dawley rats by feeding a high-fat, high-sugar diet (HFHSD) for 10 weeks, and metabolic status was evaluated using a glucose tolerance test. The weight and size of reproductive organs were measured, and Abcb1a/1b, Abcg2, Cyp19a1, and Ar expression in testes or sperm was determined by RT-PCR and Western blotting. At the same time, testosterone levels were measured by ELISA. Results: HFHSD successfully induced higher weight gain with glucose intolerance and reduced reproductive organ size. In obese rats, testicular Abcb1a and Abcb1b mRNA and P-gp protein expression were significantly higher, whereas testicular Abcg2 mRNA levels decreased. Spermatic Abcb1a, Abcb1b and Abcg2 mRNA expression also reduced in obesity. Neither testicular testosterone concentration nor Cyp19a1 and Ar mRNA expression levels changed after the 10-week obesogenic diet compared with controls. Conclusions: Overall, our study revealed infertility-related ABC transporter changes in obese male rats, suggesting that these alterations may predispose obese males to fertility impairments, even before the obesity-induced androgen dysregulation.

Obesity and overweight also increasingly affect women of childbearing age and pregnant women. In maternal obesity, the activation of metabolic, inflammatory, and oxidative stress pathways is proven, which appears to be a key step in placental and uterus function pathological changes. Several recent studies have evidenced that aquaporins (AQPs) are critical players in adipose tissue biology and are involved in the onset of obesity. Our studies aimed to investigate the changes in placental volume and vascularization and measure the AQP5 expression and total antioxidant capacity (TAC) in the placenta and uterus tissues in obese and normal-weight mothers. We also aim to measure the AQP5 plasma concentration. We found AQP5 dominance in the uterus and plasma at 34 weeks of normal pregnancy. The placental volume increased, and the vascularization decreased in obese mothers compared to the control. The AQP5 expression increased in the uterus of the obese group and did not change in the placenta. The TAC decreased in the plasma of overweight mothers. We hypothesize that increased AQP5 expression prolongs the length of pregnancy and inhibits the onset of contractions. Based on our findings, we can develop diagnostic tests and provide new targets for tocolytic drug development.

Background: Obesity and overweight are also becoming more prevalent among women of childbearing age and pregnant women. In maternal obesity, the activation of metabolic, inflammatory, and oxidative stress pathways is proven, which appears to be a key step in the pathological changes observed in placental and uterine function. Several recent studies have evidenced that aquaporins (AQPs) are critical players in adipose tissue biology and are involved in the onset of obesity. Methods: Our studies aimed to investigate the changes in placental volume and vascularization and measure the AQP5 expression and total antioxidant capacity (TAC) in the placenta and uterus tissues in obese and typical-weight mothers. We also aim to measure the AQP5 plasma concentration. Results: We found AQP5 dominance in the uterus and plasma at 34 weeks of normal pregnancy. The placental volume increased and the vascularization decreased in obese mothers compared to the control. The AQP5 expression increased in the uterus of the obese group and did not change in the placenta. The TAC decreased in the plasma of overweight mothers. Conclusions: We hypothesize that increased AQP5 expression prolongs the length of pregnancy and inhibits the onset of contractions. Based on our findings, we can develop diagnostic tests and provide new targets for tocolytic drug development.