P-316 Fertility, pregnancy outcomes, and perinatal results related to experimental endometriosis in a murine model
Authors: Franzoni Smargiassi N , Mantovani da Luz C , Rosa e Silva J  C , Navarro P  A 
Published: July 2024

Abstract

Study question
Does the transplantation of endometrial tissue fragments into the peritoneal wall of female mice reduce natural fertility and lead to compromised obstetric and perinatal outcomes?

Summary answer
Experimental murine endometriosis did not compromise fertility, but females with more ectopic endometria had litters with reduced birth weight and fewer offspring at weaning.

What is known already
It has been demonstrated that endometriosis is strongly associated with subfertility and is increasingly linked to late pregnancy complications, such as those caused by placental insufficiency. At the molecular level, the presence of ectopic endometrium may perturb the endometrial hormonal, cellular, and immunological milieu, negatively influencing the decidualization, placentation, and developmental programming of the embryo. However, it remains unclear if and how such early aberrant reproductive development relates to pregnancy outcomes in endometriosis. Thus, the use of animal models may be very useful in deepening our understanding of the pathogenic mechanisms of infertility and compromised pregnancy outcomes related to endometriosis.

Study design, size, duration
C57BL/6J female mice were divided into three groups: Control (42 animals underwent sham surgery), Endometriosis1 (19 animals underwent surgery for transplantation of one fragment of endometrial tissue on each side of the peritoneal wall), and Endometriosis2 (23 animals received two fragments on each side). The maximum experiment duration was 15 weeks, including a 4-week rest period post-surgery, up to 4 weeks for mating, 3 weeks for delivery, and 4 weeks until weaning of the offspring.

Participants/materials, setting, methods
Reproductive-age female mice from the three groups had a 4-week rest period post-surgery. Then, they were paired for mating with proven fertile males and checked for the presence of a vaginal plug daily. Pregnant females were euthanized after weaning the litter at 4 weeks. Tissue from the implants was collected for histological analysis. The occurrence of pregnancy, gestation duration, litter size, pup weight at birth and weaning, and mating return were compared among the groups.

Main results and the role of chance
All females in the experimental groups were confirmed for the presence of ectopic endometrium through histology. No statistically significant differences were observed in pregnancy rates, gestation duration, litter size at birth, and the number of live pups at birth when comparing the three groups (C, E1, and E2). However, the litter weight at birth was significantly lower in group E2 (Medial (Md): 8g; Percentile (P)25: 6; P75: 10) than in groups C (Md: 10g; P25: 8; P75: 10) and E1 (Md: 10g; P25: 10; P75: 12), and significantly higher in E1 compared to C. The number of live pups at weaning was significantly lower in E2 (Md: 5; P25: 3.5; P75: 7) compared to groups C (Md: 7; P25: 5; P75: 7) and E1 (Md: 8; P25: 7; P75: 8), and significantly higher in E1 than in C. The litter weight at weaning was significantly lower in E2 (Md: 96g; P25: 67; P75: 109) than in both E1 (Md: 116g; P25: 110; P75: 128) and C (Md: 104g; P25: 96; P75: 112). The litter weight at weaning was higher in E1 compared to group C. There was no statistically significant difference in mating return rates among the three groups.

Limitations, reasons for caution
This study is limited by the use of an animal model that does not have spontaneous endometriosis.

Wider implications of the findings
Litters from the E2 group may have had impaired development during gestation, as indicated by lower birth weight and higher perinatal mortality. Although this is not an ideal translational model for studying endometriosis-related infertility, it may serve as a suitable model for evaluating gestational and perinatal outcomes associated with endometriosis.

Trial registration number
Not applicable