Fertility, Gestation Outcome and Parasite Congenital Transmissibility in Mice Infected with TcI, TcII and TcVI Genotypes of Trypanosoma cruzi

Abstract

This work aims to compare the effects of acute or chronic infections with the T. cruzi genotypes TcI (X10 strain), TcII (Y strain) and TcVI (Tulahuen strain) on fertility, gestation, pup growth and the possible vertical transmission of parasites in BALB/c mice. The occurrence of congenital infection was evaluated by microscopic examination of blood and/or qPCR on blood and heart in newborn pups and/or older offspring submitted to cyclophosphamide-induced immunosuppression in order to detect possible cryptic congenital infection. Altogether, the results show that: i) for the three strains tested, acute infection occurring after the embryo implantation in the uterus (parasite inoculation 4 days before mating), or close to delivery (parasite inoculation on day 13 of gestation), prevents or severely jeopardizes gestation outcome (inducing pup mortality and intra-uterine growth retardation); ii) for the three strains tested, gestation during chronic infection results in intra-uterine growth retardation, whereas re-inoculation of TcVI parasites during gestation in such chronically infected mice, in addition, strongly increases pup mortality; iii) congenital infection remains a rare consequence of infection (occurring in approximately 4% of living pups born to acutely infected dams); iv) PCR, detecting parasitic DNA and not living parasites, is not convenient to detect congenial infection close to delivery; v) transmission of parasites by breast milk is unlikely. This study should encourage further investigations using other parasite strains and genotypes to explore the role of virulence and other factors, as well as the mechanisms of such effects on gestation and on the establishment of congenital infection.

Congenital Chagas disease as an ecological model of interactions between Trypanosoma cruzi parasites, pregnant women, placenta and fetuses

“…1). Similar results are observed in experimental infections, in which parasitemias in transmitting dams (acutely infected) are particularly high compared to nontransmitting animals (Cencig et al, 2013).…”

“…A recent work of our team studied congenital transmission from mouse dams acutely or chronically infected with the T. cruzi strains X10 (TcI), Y (TcII) and Tulahuen (TcVI). It showed that congenital infection (detected by blood microscopic examination in offspring submitted to cyclophosphamide-induced immunosuppression in order to activate possible cryptic infection) occurred in approximately 4% of living pups born to dams acutely infected with Y or Tulahuen strains, but not with X10 and not in those born to chronically infected animals (Cencig et al, 2013). So, mice and rats display lower yield of maternal-fetal parasite transmission than humans.…”

“…Neonatal morbidity and mortality are much higher when acute or reactivated infection (co-infection with HIV) occur during pregnancy (see Section 4; Freilij et al, 1995b;Moretti et al, 2005;Scapellato et al, 2009), as well as, likely, when chronically infected pregnant women suffer from re-infections (see Section 9; Torrico et al, 2006). Experiments in mice also show acute infection and reinfections in chronic phase inducing fetal resorptions and/or pup mortality (Mjihdi et al, 2002;Solana et al, 2002;Cencig et al, 2013; see Section 9), in relation to high blood parasite-and TNF-␣-levels (Mjihdi et al, 2002(Mjihdi et al, , 2004Solana et al, 2009). (1) Reactivated Chagas disease: data according to Scapellato et al, 2009; (2) acute Chagas disease: data according to Bittencourt (1992) and Moretti et al, 2005; (3) chronic Chagas disease: average transmission rates in endemic and non endemic countries (EC and NEC, respectively) according to Howard et al (2014).…”

Seroprevalence of Trypanosoma cruzi Among Mothers and Children in Rural Mayan Communities and Associated Reproductive Outcomes

“…30,31 Another study suggests that intrauterine growth retardation occurs during chronic murine T. cruzi infection, but it did not note any difference between other reproductive outcomes of infected and uninfected mice. 32,33 Studies in non-human primates have not observed differences in fertility, menstrual cycle parameters, or numbers of stillbirths or miscarriages between uninfected and infected females. 34 Congenital Chagas disease in humans has been associated with pre-term labor, low birth weight, and neonatal complications.…”

Prevalencia de anticuerpos anti-T. cruzi en mujeres edad fértil en Socotá, Boyacá, 2014

“…Según la Organización Mundial de la Salud (OMS), se estima que al menos dos millones de mujeres en edad fértil en América Latina están infectadas por T. cruzi y en fase crónica, con una incidencia de infección congénita de alrededor de 15.000 casos por año (9), y que en los países o regiones con mayor endemia puede haber más posibilidades de transmisión congénita (10). En los estudios en modelos animales se ha observado que los ratones infectados con el parásito T. cruzi durante la gestación, no ganan el mismo peso que los que no están infectados; además, la tasa de mortalidad de los recién nacidos de madres infectadas es mayor que en los de madres no infectadas (11).…”